Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to expl...Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.展开更多
Staphylococcus aureus(S. aureus) is a common pathogenic bacterium in animal husbandry that can cause diseases such as mastitis, skin infections, arthritis, and other ailments. The formation of biofilms threatens and e...Staphylococcus aureus(S. aureus) is a common pathogenic bacterium in animal husbandry that can cause diseases such as mastitis, skin infections, arthritis, and other ailments. The formation of biofilms threatens and exacerbates S. aureus infection by allowing the bacteria to adhere to pathological areas and livestock product surfaces, thus triggering animal health crises and safety issues with livestock products. To solve this problem, in this review, we provide a brief overview of the harm caused by S. aureus and its biofilms on livestock and animal byproducts(meat and dairy products). We also describe the ways in which S. aureus spreads in animals and the threats it poses to the livestock industry. The processes and molecular mechanisms involved in biofilm formation are then explained. Finally, we discuss strategies for the removal and eradication of S. aureus and biofilms in animal husbandry, including the use of antimicrobial peptides, plant extracts, nanoparticles, phages, and antibodies. These strategies to reduce the spread of S. aureus in animal husbandry help maintain livestock health and improve productivity to ensure the ecologically sustainable development of animal husbandry and the safety of livestock products.展开更多
Slightly acidic electrolyzed water(SAEW)has proven to be an efficient and novel sanitizer in food and agriculture field.This study assessed the efficacy of SAEW(30 mg/L)at 40℃on the inactivation of foodbome pathogens...Slightly acidic electrolyzed water(SAEW)has proven to be an efficient and novel sanitizer in food and agriculture field.This study assessed the efficacy of SAEW(30 mg/L)at 40℃on the inactivation of foodbome pathogens and detachment of multi-resistant Staphylococcus aureus(MRSA)biofilm.Furthermore.the underlying mechanism of MRS A biofilm under heated SAEW at 40℃treatment on metabolic profiles was investigated.The results showed that the heated SAEW at 40℃significantly effectively against foodbome pathogens of 1.96-7.56(lg(CFU/g))reduction in pork,chicken,spinach,and lettuce.The heated SAEW at 40℃treatment significantly reduced MRS A biofilm cells by 2.41(lg(CFU/cm^(2))).The synergistic effect of SAEW treatment showed intense anti-biofilm activity in decreasing cell density and impairing biofilm cell membranes.Global metabolic response of MRSA biofilms,treated by SAEW at 40℃,revealed the alterations of intracellular metabolites,including amino acids,organic acid,fatty acid,and lipid.Moreover,signaling pathways involved in amino acid metabolism,energy metabolism,nucleotide synthesis,carbohydrate metabolites,and lipid biosynthesis were functionally disrupted by the SAEW at 40℃treatment.As per our knowledge,this is the first research to uncover the potential mechanism of heated SAEW treatment against MRSA biofilm on food contact surface.展开更多
Staphylococcus aureus is a serious foodborne pathogen threatening food safety and public health.Especially the emergence of methicillin-resistant Staphylococcus aureus(MRSA)increased the difficulty of S.aureus treatme...Staphylococcus aureus is a serious foodborne pathogen threatening food safety and public health.Especially the emergence of methicillin-resistant Staphylococcus aureus(MRSA)increased the difficulty of S.aureus treatment.Staphyloxanthin is a crucial virulence factor of S.aureus.Blocking staphyloxanthin production could help the host immune system counteract the invading S.aureus cells.In this study,we first screened for staphyloxanthin inhibitors using a virtual screening method.The outcome of the virtual screening method resulted in the identification of eugenol(300μg/mL),which significantly inhibits the staphyloxanthin production in S.aureus ATCC 29213,S.aureus Newman,MRSA ATCC 43300 and MRSA ATCC BAA1717by 84.2%,63.5%,68.1%,and 79.5%,respectively.The outcome of the growth curve assay,field-emission scanning electron,and confocal laser scanning microscopy analyses confirmed that eugenol at the test concentration did not affect the morphology and growth of S.aureus.Moreover,the survival rate of S.aureus ATCC 29213 and MRSA ATCC 43300 under H_(2)O_(2) pressure decreased to 51.9%and 45.5%in the presence of eugenol,respectively.The quantitative RT-PCR and molecular simulation studies revealed that eugenol targets staphyloxanthin biosynthesis by downregulating the transcription of the crtM gene and inhibiting the activity of the CrtM enzyme.Taken together,we first determined that eugenol was a prominent compound for staphyloxanthin inhibitor to combat S.aureus especially MRSA infections.展开更多
Sensitive detection of Staphylococcus aureus enterotoxin B(SEB)is of importance for preventing food poisoning from threatening human health.In this work,an electrochemical and colorimetric dual-signal detection assay ...Sensitive detection of Staphylococcus aureus enterotoxin B(SEB)is of importance for preventing food poisoning from threatening human health.In this work,an electrochemical and colorimetric dual-signal detection assay of SEB was developed.The probe(Ab2/AuPt@Fe-N-C)was bound to SEB captured by Ab1,where the Ab2/AuPt@Fe-N-C triggered methylene blue degradation and resulted in the decrease of electrochemical signal.Furthermore,the probe catalyzed the oxidation of 3,3’,5,5’-tetramethyl biphenyl to generate a colorimetric absorbance at 652 nm.Once the target was captured and formed a sandwich-like complex,the color changed from colorless to blue.SEB detection by colorimetric and electrochemical methods showed a linear relationship in the concentration ranges of 0.0002-10.0000 and 0.0005-10.0000 ng/mL,with limits of detection of 0.0667 and 0.1670 pg/mL,respectively.The dual-signal biosensor was successfully used to detect SEB in milk and water samples,which has great potential in toxin detection in food and the environment.展开更多
BACKGROUND Although neonatal Staphylococcus aureus pneumonia is common and usually curable,it can also be refractory and life-threatening.Herein,we report a case of severe neonatal community-acquired methicillin-resis...BACKGROUND Although neonatal Staphylococcus aureus pneumonia is common and usually curable,it can also be refractory and life-threatening.Herein,we report a case of severe neonatal community-acquired methicillin-resistant Staphylococcus aureus(CA-MRSA)necrotizing pneumonia with bilateral recurrent pyopneumothorax,respiratory failure,heart failure,and cardiac arrest.We hope our report will add to the understanding of this disease.CASE SUMMARY An 18-d-old boy presented with cough for five days,fever for three days,and dyspnea for two days.Preadmission chest radiograph revealed high-density shadows in both lungs.On admission,his oxygen saturation fluctuated around 90%under synchronized intermittent mandatory ventilation.He was unconscious,with dyspnea,weak heart sounds and hepatomegaly.Moist crackles were present throughout his left lung,while the breath sounds in the right lung were decreased.After high-frequency oscillatory ventilation,empiric antimicrobials(meropenem and vancomycin),improved circulation,and right pleural cavity drainage for right pneumothorax(approximately 90%compression),his oxygen saturation level stayed above 95%,and recruitment of the right lung was observed.His condition did not deteriorate until the 5th day of hospitalization(DOH 5).On the morning of DOH 5,his oxygen saturation decreased.Subsequent chest radiograph showed bilateral pneumothorax with nearly 100%compression of the left lung.Desaturation was not relieved after urgent left pleural cavity drainage,and cardiac arrest occurred soon thereafter.Although his spontaneous heartbeat returned through emergency resuscitation and salvage antibacterial therapy(linezolid and levofloxacin)was administered given the detection and antimicrobial susceptibility of MRSA,he showed no improvement,with recurrent pyopneumothorax and continued drainage of purulent fluid and necrotic lung tissue fragments from the pleural cavity.Eventually,his parents refused extracorporeal membrane oxygenation(ECMO)and gave up all the treatments,and the newborn passed away soon after withdrawal on DOH 13.CONCLUSION Neonatal MRSA pneumonia can be refractory and lethal,especially in cases where necrotizing pneumonia leads to extensive lung necrosis and recurrent pneumothorax.Despite treatment with linezolid and other medical measures,it may still be ineffective.Currently,ECMO has been a remedial therapy,but if the lung tissue is too severely eroded to be repaired,it may be useless unless the infection can be controlled and lung transplantation can be performed.Regardless of whether ECMO is initiated,the key to successful treatment is to achieve control over the pneumonia caused by MRSA as soon as possible and to reverse lung injury as much as possible.展开更多
Objective To investigate the genotypic diversity of Methicillin-resistant Staphylococcus aureus (MRSA) isolated from pigs and retail foods from different geographical areas in China and further to study the routes a...Objective To investigate the genotypic diversity of Methicillin-resistant Staphylococcus aureus (MRSA) isolated from pigs and retail foods from different geographical areas in China and further to study the routes and rates of transmission of this pathogen from animals to food. Methods Seventy-one MRSA isolates were obtained from pigs and retail foods and then characterized by multi-locus sequencing typing (MLST), spa typing, multiple-locus variable number of tandem repeat analysis (MLVA), pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. Results All isolated MRSA exhibited multi-drug resistance (MDR). Greater diversity was found in food-associated MRSA (7 STs, 8 spa types, and 10 MLVA patterns) compared to pig-associated MRSA (3 STs, 1 spa type, and 6 MLVA patterns). PFGE patterns were more diverse for pig-associated MRSA than those of food-associated isolates (40 vs. 11 pulse types). Among the pig-associated isolates, CC9-ST9-t899-MC2236 was the most prevalent clone (96.4%), and CC9-ST9-t437-MC621 (20.0%) was the predominant clone among the food-associated isolates. The CC9-ST9 isolates showed significantly higher antimicrobial resistance than other clones. Interestingly, CC398-ST398-t034 clone was identified from both pig- and food-associated isolates. Of note, some community- and hospital-associated MRSA strains (t030, t172, t1244, and t4549) were also identified as food-associated isolates. Conclusion CC9-ST9-t899-MC2236-MDR was the most predominant clone in pigs, but significant genetic diversity was observed in food-associated MRSA. Our results demonstrate the great need for improved surveillance of MRSA in livestock and food and effective prevention strategies to limit MDR-MRSA infections in China.展开更多
Objective:To determine the antibiotic resistance profile(ARP)of Staphylococcus(S.)aureus isolates and molecular typing of the methicillin-resistant S.aureus(MRSA)isolates from Tuanku Mizan Armed Forces Hospital(TMAFH)...Objective:To determine the antibiotic resistance profile(ARP)of Staphylococcus(S.)aureus isolates and molecular typing of the methicillin-resistant S.aureus(MRSA)isolates from Tuanku Mizan Armed Forces Hospital(TMAFH),Kuala Lumpur.Methods:The ARP and presence of the pvl gene were determined for 209 S.aureus isolates from clinical specimens.Of these,123 were methicillin-susceptible S.aureus(MSSA)isolates and 86 were MRSA isolates.All MRSA isolates were characterized using SCCmec typing and spa typing.Descriptive analysis was performed to compare the demographic data with the phenotypic and genotypic variables of the S.aureus isolates.Results:No vancomycin-intermediate and-resistant S.aureus(VISA and VRSA,respectively)were detected among the study isolates.The MSSA isolates showed low resistance rates to all tested antibiotics,were commonly invasive(28/42,66.7%),and mostly harboured pvl(35/42,83.3%).Meanwhile,MRSA isolates showed high resistance to penicillin(86/86,100%),ampicillin(86/86,100%),sulbactam/ampicillin(86/86,100%),cefuroxime(81/86,94.19%),cefoperazone(76/86,88.37%),azithromycin(56/86,65.12%),and erythromycin(54/86,62.79%).The majority of MRSA isolates were of SCCmec type IVh(65/86,75.58%),spa type t032(55/85,63.95%),and grouped into spaCC-t022(66/85,77.65%).The t032 type was found to be associated with resistance traits to azithromycin and erythromycin(P<0.05).We also found several spa types that are typically associated with hospital-,community-,and livestock-associated MRSA co-existing in our MRSA population.Conclusions:This study reflected the consistent absence of VISA and VRSA and corroborated the clonal shifting of MRSA isolates in the Malaysian MRSA isolates.展开更多
Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to stu...Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to study the role of two molecules during S.aureus infection.However,the contribution of HLA DP to S.aureus infection is unknown yet.Methods:In this study,we have produced HLA DP401 and HLA DRA0101 humanized mice by microinjection of C57BL/6J zygotes.Neo-floxed IAβ+/-mice were crossbred with Ella-Cre and further crossbred with HLA DP401 or HLA-DRA0101 humanized mice.After several rounds of traditional crossbreeding,we finally obtained HLA DP401-IAβ-/-and HLA DRA-IAβ-/-humanized mice,in which human DP401 or DRA0101 molecule was introduced into IAβ-/-mice deficient in endogenous murine MHC classⅡmolecules.A transnasal infection murine model of S.aureus pneumonia was induced in the humanized mice by administering 2×108CFU of S.aureus Newman dropwise into the nasal cavity.The immune responses and histopathology changes were further assessed in lungs in these infected mice.Results:We evaluated the local and systemic effects of S.aureus delivered intranasally in HLA DP401-IAβ-/-and HLA DRA-IAβ-/-transgenic mice.S.aureus Newman infection significantly increased the m RNA level of IL 12p40 in lungs in humanized mice.An increase in IFN-γand IL-6 protein was observed in HLA DRA-IAβ-/-mice.We observed a declining trend in the percentage of F4/80+macrophages in lungs in HLA DP401-IAβ-/-mice and a decreasing ratio of CD4+to CD8+T cells in lungs in IAβ-/-mice and HLA DP401-IAβ-/-mice.A decreasing ratio of Vβ3+to Vβ8+T cells was also found in the lymph node of IAβ-/-mice and HLA DP401-IAβ-/-mice.S.aureus Newman infection resulted in a weaker pathological injury in lungs in IAβ-/-genetic background mice.Conclusion:These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S.aureus pneumonia and study what role DP molecule plays in S.aureus infection.展开更多
BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci.AIM To explore the value of teicoplanin combined with conventional(vancomycin only)anti-inf...BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci.AIM To explore the value of teicoplanin combined with conventional(vancomycin only)anti-infective therapy for the treatment of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis pulmonary infections.METHODS A total of 86 patients with methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis pulmonary infections,treated in our hospital between January 2018 and February 2020,were assigned to the study and control groups using a random number table method,with 43 patients in each group.The control group received conventional treatment(vancomycin),and the study group received both teicoplanin and conventional treatment.The following indicators were assessed in both groups:the time required for symptom relief,treatment effectiveness,serum levels of inflammatory factors(procalcitonin,interleukin-1β,tumor necrosis factor-α,C-reactive protein),clinical pulmonary infection scores before and after treatment,and the incidence of adverse reactions.RESULTS Patients in the study group were observed to have faster cough and expectoration resolution,white blood cell count normalization,body temperature normalization,and rales disappearance than patients in the control group(all P<0.05);the total rate of effectiveness was 93.02%in the study group,higher than the 76.74%in the control group(P<0.05).The pre-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were similar among the patients in both groups.However,the post-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were significantly lower in the study group than in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the groups.CONCLUSION Compared with conventional(vancomycin only)therapy,teicoplanin and vancomycin combination therapy for patients with pulmonary methicillinresistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections can improve patient clinical symptoms,modulate serum inflammatory factor levels,and improve treatment efficacy,without increasing the risk of adverse reactions.展开更多
Objective:To investigate the mechanism of antibacterial activity of luteoiin(LUT) against methicillin-resistant Staphylococcus aureus(MRSA).Methods:The mechanism of anti-MRSA activity of LUT was analyzed by the viabil...Objective:To investigate the mechanism of antibacterial activity of luteoiin(LUT) against methicillin-resistant Staphylococcus aureus(MRSA).Methods:The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent ATPase inhibitors,and peptidoglycan(PGN) derived from Staphylococcus aureus(S.aureus).Also,transmission electron microscopy was used to monitor survival characteristics and changes in S.aureus morphology.Results:Compared to the LUT alone,the optical density of suspensions treated with the combination of 125 μg/mL Tris and 230 μg/mL DCCD were reduced to 60%and 46%,respectively.PGN(15.6 μg/mL) gradually impeded the activity of LUT,and PGN(62.5 μg/mL) completely blocked the activity of LUT on S.aureus.Conclusions:Increased susceptibility to LUT with me Tris and DCCD combinations is evident in all tested MRSA isolates.The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase.S.aureus PGN directly blocks the antibacterial activity of LUT,suggesting the direct binding of LUT with PGN.These findings may be validated for the development of antibacterial agent for low MRSA resistance.展开更多
A one-year-old baby girl with one-month history of recurrent pus fluid exuding from her left preauricular sinus orifice, who failed multiple courses of surgical drainage of the abscess and persistent debridement for t...A one-year-old baby girl with one-month history of recurrent pus fluid exuding from her left preauricular sinus orifice, who failed multiple courses of surgical drainage of the abscess and persistent debridement for the wound, presented with MRSA infection. The patient was treated with linezolid for three days. Her pain and paresthesia resolved, and C-reactive protein decreased to normal.展开更多
This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine...This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and Nhydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV–vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane–DAPT–VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells,in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.展开更多
Objective: To investigate the antibacterial activity of SHHextracted with either water or ethanol against methicillin-resistant Staphylococcus aureus(MRSA) and combinatory antimicrobial effect with ciprofloxacin(CIP) ...Objective: To investigate the antibacterial activity of SHHextracted with either water or ethanol against methicillin-resistant Staphylococcus aureus(MRSA) and combinatory antimicrobial effect with ciprofloxacin(CIP) by time kill assay and checkerboard dilution test. Methods: The antibacterial activity determined by broth dilution method indicated that the antibacterial activity of Sami-Hyanglyun-Hwan(SHH) water extract(SHHW) and SHH ethanol extract(SHHE) ranged from 250 to 2000 μg/m L and 125 to 1000 μg/m L against MRSA, respectively. Results: In the checkerboard method, the combinations of SHHE with CIP had a partial synergistic or synergistic effect against MRSA. The time-kill curves showed that a combined SHHE and CIP treatment reduced the bacterial counts dramatically after 24 h. Conclusions: The present study demonstrates the therapeutic ability of SHHE against MRSA infections.展开更多
BACKGROUND Vancomycin remains a first-line treatment drug as per the treatment guidelines for methicillin-resistant Staphylococcus aureus(MRSA)bacteremia.However,a number of gram-positive cocci have developed resistan...BACKGROUND Vancomycin remains a first-line treatment drug as per the treatment guidelines for methicillin-resistant Staphylococcus aureus(MRSA)bacteremia.However,a number of gram-positive cocci have developed resistance to several drugs,including glycopeptides.Therefore,there is an urgent need for effective and innovative antibacterial drugs to treat patients with infections caused by drugresistant bacteria.CASE SUMMARY A 24-year-old male was admitted to hospital owing to lumbago,fever,and hematuria.Computed tomography(CT)results showed an abscess in the psoas major muscle of the patient.Repeated abscess drainage and blood culture suggested MRSA,and vancomycin was initiated.However,after day 10,CT scans showed abscesses in the lungs and legs of the patient.Therefore,treatment was switched to daptomycin.Linezolid was also added considering inflammation in the lungs.After 10 d of the dual-drug anti-MRSA treatment,culture of the abscess drainage turned negative for MRSA.On day 28,the patient was discharged without any complications.CONCLUSION This case indicates that daptomycin combined with linezolid is an effective remedy for bacteremia caused by MRSA with pulmonary complications.展开更多
Staphylococcus aureus(S.aureus) is one of the most common human pathogens,causing a wide range of afflictions from minor infections of the skin to serious wound infections,bacteraemia,pneumonia and endocarditis. Methi...Staphylococcus aureus(S.aureus) is one of the most common human pathogens,causing a wide range of afflictions from minor infections of the skin to serious wound infections,bacteraemia,pneumonia and endocarditis. Methicillin,the first semisynthetic derivative of penicillin,was a new hope to treat penicillin resistant 5.aureus in the early 1960s.Nevertheless,only one year after its introduction,the first methicillin-resistant 5.aureus (MRSA) strains were detected.There is no golden rule in the control of MRSA.Nevertheless,using surveillance cultures of patients and healthcare personnel,strictly enforced contact precautions,and judicious use of broad-spectrum antibiotics have helped several countries,including Finland,Denmark,and the Netherlands to keep MRSA at a very low level.Conversely,countries including China,Japan,US,Italy,Greece,UK, where stringent counter-measure were not able to be installed,MRSA have become hyper-endemic.Control of MRSA in those countries were obliged to concentrate available resources to prevent MRSA infections only at patients at high risk of serious morbidity and mortality.展开更多
Objective: To investigate the synergistic effect between rhein(RHE) and oxacillin against Staphylococcus aureus(MRSA) at the gene level. Method: A minimum inhibitory concentration and checkerboard dilution test were c...Objective: To investigate the synergistic effect between rhein(RHE) and oxacillin against Staphylococcus aureus(MRSA) at the gene level. Method: A minimum inhibitory concentration and checkerboard dilution test were conducted to evaluate antibacterial activity. Reverse transcriptase polymerase chain reaction was conducted to investigate the gene expressions. Results: RHE exhibited a minimum inhibitory concentration of 62.5-250.0 μg/mL against various MRSA strains and the reference strain, respectively. As revealed by the checkerboard assay, a combination of RHE and oxacillin exhibited synergistic or partially synergistic effects against MRSA strains. RHE decreased the expressions of mecA/blaZ in a dose-dependent manner. RHE also decreased the expressions of the regulator genes mecI/blaI and mecR1/blaR1. Conclusions: We suggest that RHE affects the activity of mecR1/blaR1, which is located in the cell membrane of MRSA and results in the suppression of mecA/mecI/mecR1 and blaZ/blaI/blaR1 gene expressions.展开更多
基金financially supported by the National Natural Science Foundation of China(82101069,82102537,82160411,82002278)the Natural Science Foundation of Chongqing Science and Technology Commission(CSTC2021JCYJ-MSXMX0170,CSTB2022BSXM-JCX0039)+2 种基金the First Affiliated Hospital of Chongqing Medical University Cultivating Fund(PYJJ2021-02)the Beijing Municipal Science&Technology Commission(Z221100007422130)the Youth Incubation Program of Medical Science and Technology of PLA(21QNPY116).
文摘Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.
基金supported by the National Natural Science Foundation of China (31930106 and U22A20514, U23A20232)the National Key R&D Program of China (2022YFD1300404)+2 种基金the 2115 Talent Development Program of China Agricultural University (1041-00109019)the Pinduoduo-China Agricultural University Research Fund (PC2023A01001)the Special Fund for Henan Agriculture Research System (HARS-2213-Z1)。
文摘Staphylococcus aureus(S. aureus) is a common pathogenic bacterium in animal husbandry that can cause diseases such as mastitis, skin infections, arthritis, and other ailments. The formation of biofilms threatens and exacerbates S. aureus infection by allowing the bacteria to adhere to pathological areas and livestock product surfaces, thus triggering animal health crises and safety issues with livestock products. To solve this problem, in this review, we provide a brief overview of the harm caused by S. aureus and its biofilms on livestock and animal byproducts(meat and dairy products). We also describe the ways in which S. aureus spreads in animals and the threats it poses to the livestock industry. The processes and molecular mechanisms involved in biofilm formation are then explained. Finally, we discuss strategies for the removal and eradication of S. aureus and biofilms in animal husbandry, including the use of antimicrobial peptides, plant extracts, nanoparticles, phages, and antibodies. These strategies to reduce the spread of S. aureus in animal husbandry help maintain livestock health and improve productivity to ensure the ecologically sustainable development of animal husbandry and the safety of livestock products.
基金supported by Brain Korea (BK)21 Plus Project (4299990913942)funded by the Korean Government,Koreathe Collabo Project funded by the Ministry of SMEs and Startups (C1016120-01-02)the National Research Foundation of Korea (NRF) (2018007551)。
文摘Slightly acidic electrolyzed water(SAEW)has proven to be an efficient and novel sanitizer in food and agriculture field.This study assessed the efficacy of SAEW(30 mg/L)at 40℃on the inactivation of foodbome pathogens and detachment of multi-resistant Staphylococcus aureus(MRSA)biofilm.Furthermore.the underlying mechanism of MRS A biofilm under heated SAEW at 40℃treatment on metabolic profiles was investigated.The results showed that the heated SAEW at 40℃significantly effectively against foodbome pathogens of 1.96-7.56(lg(CFU/g))reduction in pork,chicken,spinach,and lettuce.The heated SAEW at 40℃treatment significantly reduced MRS A biofilm cells by 2.41(lg(CFU/cm^(2))).The synergistic effect of SAEW treatment showed intense anti-biofilm activity in decreasing cell density and impairing biofilm cell membranes.Global metabolic response of MRSA biofilms,treated by SAEW at 40℃,revealed the alterations of intracellular metabolites,including amino acids,organic acid,fatty acid,and lipid.Moreover,signaling pathways involved in amino acid metabolism,energy metabolism,nucleotide synthesis,carbohydrate metabolites,and lipid biosynthesis were functionally disrupted by the SAEW at 40℃treatment.As per our knowledge,this is the first research to uncover the potential mechanism of heated SAEW treatment against MRSA biofilm on food contact surface.
基金supported by the National Natural Science Foundation of China (31972169 and 32001798)。
文摘Staphylococcus aureus is a serious foodborne pathogen threatening food safety and public health.Especially the emergence of methicillin-resistant Staphylococcus aureus(MRSA)increased the difficulty of S.aureus treatment.Staphyloxanthin is a crucial virulence factor of S.aureus.Blocking staphyloxanthin production could help the host immune system counteract the invading S.aureus cells.In this study,we first screened for staphyloxanthin inhibitors using a virtual screening method.The outcome of the virtual screening method resulted in the identification of eugenol(300μg/mL),which significantly inhibits the staphyloxanthin production in S.aureus ATCC 29213,S.aureus Newman,MRSA ATCC 43300 and MRSA ATCC BAA1717by 84.2%,63.5%,68.1%,and 79.5%,respectively.The outcome of the growth curve assay,field-emission scanning electron,and confocal laser scanning microscopy analyses confirmed that eugenol at the test concentration did not affect the morphology and growth of S.aureus.Moreover,the survival rate of S.aureus ATCC 29213 and MRSA ATCC 43300 under H_(2)O_(2) pressure decreased to 51.9%and 45.5%in the presence of eugenol,respectively.The quantitative RT-PCR and molecular simulation studies revealed that eugenol targets staphyloxanthin biosynthesis by downregulating the transcription of the crtM gene and inhibiting the activity of the CrtM enzyme.Taken together,we first determined that eugenol was a prominent compound for staphyloxanthin inhibitor to combat S.aureus especially MRSA infections.
基金This work was financially supported by Major Science and Technology Project of Yunnan Province(202302AE090022)Key Research and Development Program of Yunnan(202203AC100010)+4 种基金the National Natural Science Foundation of China(32160597,32160236,32371463)National Key Research and Development Program of China(2022YFC2601604)Cardiovascular Ultrasound Innovation Team of Yunnan Province(202305AS350021)Spring City Plan:the High-level Talent Promotion and Training Project of Kunming(2022SCP001)the second phase of“Double-First Class”Program Construction of Yunnan University.
文摘Sensitive detection of Staphylococcus aureus enterotoxin B(SEB)is of importance for preventing food poisoning from threatening human health.In this work,an electrochemical and colorimetric dual-signal detection assay of SEB was developed.The probe(Ab2/AuPt@Fe-N-C)was bound to SEB captured by Ab1,where the Ab2/AuPt@Fe-N-C triggered methylene blue degradation and resulted in the decrease of electrochemical signal.Furthermore,the probe catalyzed the oxidation of 3,3’,5,5’-tetramethyl biphenyl to generate a colorimetric absorbance at 652 nm.Once the target was captured and formed a sandwich-like complex,the color changed from colorless to blue.SEB detection by colorimetric and electrochemical methods showed a linear relationship in the concentration ranges of 0.0002-10.0000 and 0.0005-10.0000 ng/mL,with limits of detection of 0.0667 and 0.1670 pg/mL,respectively.The dual-signal biosensor was successfully used to detect SEB in milk and water samples,which has great potential in toxin detection in food and the environment.
基金Supported by the Scientific and Technological Project of Shiyan City of Hubei Province,No.21Y32the Medical Research Project of Hubei Pediatric Alliance,No.HPAMRP202114.
文摘BACKGROUND Although neonatal Staphylococcus aureus pneumonia is common and usually curable,it can also be refractory and life-threatening.Herein,we report a case of severe neonatal community-acquired methicillin-resistant Staphylococcus aureus(CA-MRSA)necrotizing pneumonia with bilateral recurrent pyopneumothorax,respiratory failure,heart failure,and cardiac arrest.We hope our report will add to the understanding of this disease.CASE SUMMARY An 18-d-old boy presented with cough for five days,fever for three days,and dyspnea for two days.Preadmission chest radiograph revealed high-density shadows in both lungs.On admission,his oxygen saturation fluctuated around 90%under synchronized intermittent mandatory ventilation.He was unconscious,with dyspnea,weak heart sounds and hepatomegaly.Moist crackles were present throughout his left lung,while the breath sounds in the right lung were decreased.After high-frequency oscillatory ventilation,empiric antimicrobials(meropenem and vancomycin),improved circulation,and right pleural cavity drainage for right pneumothorax(approximately 90%compression),his oxygen saturation level stayed above 95%,and recruitment of the right lung was observed.His condition did not deteriorate until the 5th day of hospitalization(DOH 5).On the morning of DOH 5,his oxygen saturation decreased.Subsequent chest radiograph showed bilateral pneumothorax with nearly 100%compression of the left lung.Desaturation was not relieved after urgent left pleural cavity drainage,and cardiac arrest occurred soon thereafter.Although his spontaneous heartbeat returned through emergency resuscitation and salvage antibacterial therapy(linezolid and levofloxacin)was administered given the detection and antimicrobial susceptibility of MRSA,he showed no improvement,with recurrent pyopneumothorax and continued drainage of purulent fluid and necrotic lung tissue fragments from the pleural cavity.Eventually,his parents refused extracorporeal membrane oxygenation(ECMO)and gave up all the treatments,and the newborn passed away soon after withdrawal on DOH 13.CONCLUSION Neonatal MRSA pneumonia can be refractory and lethal,especially in cases where necrotizing pneumonia leads to extensive lung necrosis and recurrent pneumothorax.Despite treatment with linezolid and other medical measures,it may still be ineffective.Currently,ECMO has been a remedial therapy,but if the lung tissue is too severely eroded to be repaired,it may be useless unless the infection can be controlled and lung transplantation can be performed.Regardless of whether ECMO is initiated,the key to successful treatment is to achieve control over the pneumonia caused by MRSA as soon as possible and to reverse lung injury as much as possible.
基金funded by the National Key R&D Program of China(2016YFD0401102)(the National Key Research and Development Program of China,the Ministry of Science and Technology of China)China Food Safety Talent Competency Development Initiative:CFSA 523 Program(1311613106702)
文摘Objective To investigate the genotypic diversity of Methicillin-resistant Staphylococcus aureus (MRSA) isolated from pigs and retail foods from different geographical areas in China and further to study the routes and rates of transmission of this pathogen from animals to food. Methods Seventy-one MRSA isolates were obtained from pigs and retail foods and then characterized by multi-locus sequencing typing (MLST), spa typing, multiple-locus variable number of tandem repeat analysis (MLVA), pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. Results All isolated MRSA exhibited multi-drug resistance (MDR). Greater diversity was found in food-associated MRSA (7 STs, 8 spa types, and 10 MLVA patterns) compared to pig-associated MRSA (3 STs, 1 spa type, and 6 MLVA patterns). PFGE patterns were more diverse for pig-associated MRSA than those of food-associated isolates (40 vs. 11 pulse types). Among the pig-associated isolates, CC9-ST9-t899-MC2236 was the most prevalent clone (96.4%), and CC9-ST9-t437-MC621 (20.0%) was the predominant clone among the food-associated isolates. The CC9-ST9 isolates showed significantly higher antimicrobial resistance than other clones. Interestingly, CC398-ST398-t034 clone was identified from both pig- and food-associated isolates. Of note, some community- and hospital-associated MRSA strains (t030, t172, t1244, and t4549) were also identified as food-associated isolates. Conclusion CC9-ST9-t899-MC2236-MDR was the most predominant clone in pigs, but significant genetic diversity was observed in food-associated MRSA. Our results demonstrate the great need for improved surveillance of MRSA in livestock and food and effective prevention strategies to limit MDR-MRSA infections in China.
基金The study was funded by the UPNM Short Term Grant (UPNM/2019/GPJP/SP/1).
文摘Objective:To determine the antibiotic resistance profile(ARP)of Staphylococcus(S.)aureus isolates and molecular typing of the methicillin-resistant S.aureus(MRSA)isolates from Tuanku Mizan Armed Forces Hospital(TMAFH),Kuala Lumpur.Methods:The ARP and presence of the pvl gene were determined for 209 S.aureus isolates from clinical specimens.Of these,123 were methicillin-susceptible S.aureus(MSSA)isolates and 86 were MRSA isolates.All MRSA isolates were characterized using SCCmec typing and spa typing.Descriptive analysis was performed to compare the demographic data with the phenotypic and genotypic variables of the S.aureus isolates.Results:No vancomycin-intermediate and-resistant S.aureus(VISA and VRSA,respectively)were detected among the study isolates.The MSSA isolates showed low resistance rates to all tested antibiotics,were commonly invasive(28/42,66.7%),and mostly harboured pvl(35/42,83.3%).Meanwhile,MRSA isolates showed high resistance to penicillin(86/86,100%),ampicillin(86/86,100%),sulbactam/ampicillin(86/86,100%),cefuroxime(81/86,94.19%),cefoperazone(76/86,88.37%),azithromycin(56/86,65.12%),and erythromycin(54/86,62.79%).The majority of MRSA isolates were of SCCmec type IVh(65/86,75.58%),spa type t032(55/85,63.95%),and grouped into spaCC-t022(66/85,77.65%).The t032 type was found to be associated with resistance traits to azithromycin and erythromycin(P<0.05).We also found several spa types that are typically associated with hospital-,community-,and livestock-associated MRSA co-existing in our MRSA population.Conclusions:This study reflected the consistent absence of VISA and VRSA and corroborated the clonal shifting of MRSA isolates in the Malaysian MRSA isolates.
基金National Science and Technology Major Project,Grant/Award Number:2016YFD0500208,2017ZX10304402-001-012 and 2017ZX10304402-001-006Shanghai Science and Technology Commission“R&D public service platform and institutional capacity improvement project”,Grant/Award Number:21DZ2291300Shanghai Public Health Clinical Center projects,Grant/Award Number:KY-GW-2021-39,KY-GW-2019-19 and KY-GW-2019-11。
文摘Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to study the role of two molecules during S.aureus infection.However,the contribution of HLA DP to S.aureus infection is unknown yet.Methods:In this study,we have produced HLA DP401 and HLA DRA0101 humanized mice by microinjection of C57BL/6J zygotes.Neo-floxed IAβ+/-mice were crossbred with Ella-Cre and further crossbred with HLA DP401 or HLA-DRA0101 humanized mice.After several rounds of traditional crossbreeding,we finally obtained HLA DP401-IAβ-/-and HLA DRA-IAβ-/-humanized mice,in which human DP401 or DRA0101 molecule was introduced into IAβ-/-mice deficient in endogenous murine MHC classⅡmolecules.A transnasal infection murine model of S.aureus pneumonia was induced in the humanized mice by administering 2×108CFU of S.aureus Newman dropwise into the nasal cavity.The immune responses and histopathology changes were further assessed in lungs in these infected mice.Results:We evaluated the local and systemic effects of S.aureus delivered intranasally in HLA DP401-IAβ-/-and HLA DRA-IAβ-/-transgenic mice.S.aureus Newman infection significantly increased the m RNA level of IL 12p40 in lungs in humanized mice.An increase in IFN-γand IL-6 protein was observed in HLA DRA-IAβ-/-mice.We observed a declining trend in the percentage of F4/80+macrophages in lungs in HLA DP401-IAβ-/-mice and a decreasing ratio of CD4+to CD8+T cells in lungs in IAβ-/-mice and HLA DP401-IAβ-/-mice.A decreasing ratio of Vβ3+to Vβ8+T cells was also found in the lymph node of IAβ-/-mice and HLA DP401-IAβ-/-mice.S.aureus Newman infection resulted in a weaker pathological injury in lungs in IAβ-/-genetic background mice.Conclusion:These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S.aureus pneumonia and study what role DP molecule plays in S.aureus infection.
基金the Beijing Tongren Hospital,Capital Medical University Institutional Review Board(Approval No.TRECKY2020-100).
文摘BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci.AIM To explore the value of teicoplanin combined with conventional(vancomycin only)anti-infective therapy for the treatment of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis pulmonary infections.METHODS A total of 86 patients with methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis pulmonary infections,treated in our hospital between January 2018 and February 2020,were assigned to the study and control groups using a random number table method,with 43 patients in each group.The control group received conventional treatment(vancomycin),and the study group received both teicoplanin and conventional treatment.The following indicators were assessed in both groups:the time required for symptom relief,treatment effectiveness,serum levels of inflammatory factors(procalcitonin,interleukin-1β,tumor necrosis factor-α,C-reactive protein),clinical pulmonary infection scores before and after treatment,and the incidence of adverse reactions.RESULTS Patients in the study group were observed to have faster cough and expectoration resolution,white blood cell count normalization,body temperature normalization,and rales disappearance than patients in the control group(all P<0.05);the total rate of effectiveness was 93.02%in the study group,higher than the 76.74%in the control group(P<0.05).The pre-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were similar among the patients in both groups.However,the post-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were significantly lower in the study group than in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the groups.CONCLUSION Compared with conventional(vancomycin only)therapy,teicoplanin and vancomycin combination therapy for patients with pulmonary methicillinresistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections can improve patient clinical symptoms,modulate serum inflammatory factor levels,and improve treatment efficacy,without increasing the risk of adverse reactions.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Educatio(2013060380)+2 种基金the Korea governmen(MSIP)(2008-0062484)Cooperative Research Program for Agriculture Science&Technology Development(Project No.PJ00962201)Rural Development Administration,Republic of Korea
文摘Objective:To investigate the mechanism of antibacterial activity of luteoiin(LUT) against methicillin-resistant Staphylococcus aureus(MRSA).Methods:The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent ATPase inhibitors,and peptidoglycan(PGN) derived from Staphylococcus aureus(S.aureus).Also,transmission electron microscopy was used to monitor survival characteristics and changes in S.aureus morphology.Results:Compared to the LUT alone,the optical density of suspensions treated with the combination of 125 μg/mL Tris and 230 μg/mL DCCD were reduced to 60%and 46%,respectively.PGN(15.6 μg/mL) gradually impeded the activity of LUT,and PGN(62.5 μg/mL) completely blocked the activity of LUT on S.aureus.Conclusions:Increased susceptibility to LUT with me Tris and DCCD combinations is evident in all tested MRSA isolates.The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase.S.aureus PGN directly blocks the antibacterial activity of LUT,suggesting the direct binding of LUT with PGN.These findings may be validated for the development of antibacterial agent for low MRSA resistance.
文摘A one-year-old baby girl with one-month history of recurrent pus fluid exuding from her left preauricular sinus orifice, who failed multiple courses of surgical drainage of the abscess and persistent debridement for the wound, presented with MRSA infection. The patient was treated with linezolid for three days. Her pain and paresthesia resolved, and C-reactive protein decreased to normal.
基金Universiti Kebangsaan Malaysia’s research university grant scheme (DCP-2017- 003/4)。
文摘This study focused on the encapsulation of vancomycin(VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and Nhydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV–vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane–DAPT–VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells,in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.
文摘Objective: To investigate the antibacterial activity of SHHextracted with either water or ethanol against methicillin-resistant Staphylococcus aureus(MRSA) and combinatory antimicrobial effect with ciprofloxacin(CIP) by time kill assay and checkerboard dilution test. Methods: The antibacterial activity determined by broth dilution method indicated that the antibacterial activity of Sami-Hyanglyun-Hwan(SHH) water extract(SHHW) and SHH ethanol extract(SHHE) ranged from 250 to 2000 μg/m L and 125 to 1000 μg/m L against MRSA, respectively. Results: In the checkerboard method, the combinations of SHHE with CIP had a partial synergistic or synergistic effect against MRSA. The time-kill curves showed that a combined SHHE and CIP treatment reduced the bacterial counts dramatically after 24 h. Conclusions: The present study demonstrates the therapeutic ability of SHHE against MRSA infections.
基金Supported by Shantou Medical and Health Science and Technology ProgramNo. SFK [2020] 66-23
文摘BACKGROUND Vancomycin remains a first-line treatment drug as per the treatment guidelines for methicillin-resistant Staphylococcus aureus(MRSA)bacteremia.However,a number of gram-positive cocci have developed resistance to several drugs,including glycopeptides.Therefore,there is an urgent need for effective and innovative antibacterial drugs to treat patients with infections caused by drugresistant bacteria.CASE SUMMARY A 24-year-old male was admitted to hospital owing to lumbago,fever,and hematuria.Computed tomography(CT)results showed an abscess in the psoas major muscle of the patient.Repeated abscess drainage and blood culture suggested MRSA,and vancomycin was initiated.However,after day 10,CT scans showed abscesses in the lungs and legs of the patient.Therefore,treatment was switched to daptomycin.Linezolid was also added considering inflammation in the lungs.After 10 d of the dual-drug anti-MRSA treatment,culture of the abscess drainage turned negative for MRSA.On day 28,the patient was discharged without any complications.CONCLUSION This case indicates that daptomycin combined with linezolid is an effective remedy for bacteremia caused by MRSA with pulmonary complications.
文摘Staphylococcus aureus(S.aureus) is one of the most common human pathogens,causing a wide range of afflictions from minor infections of the skin to serious wound infections,bacteraemia,pneumonia and endocarditis. Methicillin,the first semisynthetic derivative of penicillin,was a new hope to treat penicillin resistant 5.aureus in the early 1960s.Nevertheless,only one year after its introduction,the first methicillin-resistant 5.aureus (MRSA) strains were detected.There is no golden rule in the control of MRSA.Nevertheless,using surveillance cultures of patients and healthcare personnel,strictly enforced contact precautions,and judicious use of broad-spectrum antibiotics have helped several countries,including Finland,Denmark,and the Netherlands to keep MRSA at a very low level.Conversely,countries including China,Japan,US,Italy,Greece,UK, where stringent counter-measure were not able to be installed,MRSA have become hyper-endemic.Control of MRSA in those countries were obliged to concentrate available resources to prevent MRSA infections only at patients at high risk of serious morbidity and mortality.
基金carried out with the support of "Cooperative Research Program for Agriculture Science & Technology Development(Project No.PJ01191902)" Rural Development Administration,Republic of Korea
文摘Objective: To investigate the synergistic effect between rhein(RHE) and oxacillin against Staphylococcus aureus(MRSA) at the gene level. Method: A minimum inhibitory concentration and checkerboard dilution test were conducted to evaluate antibacterial activity. Reverse transcriptase polymerase chain reaction was conducted to investigate the gene expressions. Results: RHE exhibited a minimum inhibitory concentration of 62.5-250.0 μg/mL against various MRSA strains and the reference strain, respectively. As revealed by the checkerboard assay, a combination of RHE and oxacillin exhibited synergistic or partially synergistic effects against MRSA strains. RHE decreased the expressions of mecA/blaZ in a dose-dependent manner. RHE also decreased the expressions of the regulator genes mecI/blaI and mecR1/blaR1. Conclusions: We suggest that RHE affects the activity of mecR1/blaR1, which is located in the cell membrane of MRSA and results in the suppression of mecA/mecI/mecR1 and blaZ/blaI/blaR1 gene expressions.