Efficacy of antimicrobials in preventing resistance in solid organ transplant recipients:A systematic review of clinical trials

BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ transplantation.AIM To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients.METHODS A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses.This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial resistance.The search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language restrictions.RESULTS After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were studied.The most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also analyzed.The antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and colistin-neomycin.Of concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two studies.CONCLUSION All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions.More high-quality randomized clinical trials are needed to corroborate these results.

Thymus serpyllum L.Essential Oil:Phytochemistry and in Vitro and in Silico Screening of Its Antimicrobial,Antioxidant and Anti-Inflammatory Properties

Thymus serpyllum L.,often known as wild thyme,has been used since ancient times due to its multifaceted culinary and medicinal attributes.It is usually utilized in folk medicine to manage different health issues.This work aimed to investigate the chemical composition and biological characteristics of T.serpyllum essential oil(EO),including its antimicrobial,antioxidant,and anti-inflammatory capabilities.Moreover,we have prompted an in-silico simulation to reveal the underlying mode of action of these properties.The chemical characterization of T.serpyllum(EO)by Gas Chromatography-Mass Spectrometry(GC-MS)indicated sabinene(17.33%),terpinen-4-ol(11.73%),phellandral(13.18%),and thymol(10.54%)as main components.The antimicrobial screening utilized the disc-diffusion technique,MIC,and MBC assays.The disc-diffusion test’s results revealed significant anti-Candida activity and notable antibacterial efficacy.The MIC and MBC tests showed that T.serpyllum EO effectively stops bacterial growth,including Gram-positive and Gram-negative strains and Candida strains.The tolerance level ratio demonstrated that this EO exhibits bactericidal and fungicidal effects on all tested bacteria and Candida strains.Also,T.serpyllum EO presented effective inhibitory activity against the 5-lipoxygenase(5-LOX)enzyme(IC50=744.19±0.1µg/mL)(p<0.05).It also effectively affected FRAP,β-carotene,DPPH,and ABTS radicals.In light of these findings,T.serpyllum holds promise for diverse applications across pharmaceuticals,nutraceuticals,and the food industry.However,further research and collaboration between traditional knowledge and modern medicine are crucial to fully realizing its potential benefits in these fields.

Core and variable antimicrobial resistance genes in the gut microbiomes of Chinese and European pigs

Monitoring the prevalence of antimicrobial resistance genes(ARGs)is vital for addressing the global crisis of antibiotic-resistant bacterial infections.Despite its importance,the characterization of ARGs and microbiome structures,as well as the identification of indicators for routine ARG monitoring in pig farms,are still lacking,particularly concerning variations in antimicrobial exposure in different countries or regions.Here,metagenomics and random forest machine learning were used to elucidate the ARG profiles,microbiome structures,and ARG contamination indicators in pig manure under different antimicrobial pressures between China and Europe.Results showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs(P<0.05).ANT(6)-Ib,APH(3')-IIIa,and tet(40)were identified as shared core ARGs between the two pig populations.Furthermore,the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical regions.Lactobacillus and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs,respectively.Forty ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100%and 98.7%,respectively.Indicators for assessing ARG contamination in Chinese and European pigs also achieved high accuracy(r=0.72-0.88).Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 ARGs.The results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.

Phytochemical Analysis and Antimicrobial Activity of Lawsonia inermis Leaf Extracts from Burkina Faso

Lawsonia inermis is a hairless plant growing in various regions of North Africa, the Indian subcontinent, and the Middle East. It possesses many medicinal attributes, including curative properties against infectious dermatoses. This study was carried out to evaluate the phytochemical profile of the crude ethanolic extract of the plant leaves and its fractions as well as their antimicrobial activities. The phytochemical profile was performed using high-performance thin-layer chromatography (HPTLC), gas chromatography-mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC). Additionally, the phenolic and flavonoid contents were determined using the Folin-Ciocalteu spectrophotometric and the aluminum trichloride methods. Antimicrobial activity was tested using disc diffusion and microdilution methods. The presence of flavonoids, tannins, sterols, and triterpenes was revealed. GC-MS detected twelve compounds main compounds consisting of saturated and unsaturated fatty acids and phenolic and terpenoid compounds among twenty-seven components. HPLC also detected high contents of phenolic acids and flavonoids. The most abundant triterpene and sterols were ursolic acid (around 43.14 g/100g DW, 13.9 g/100g dry weight (DW), and 0.68 g/100g DW) in the crude ethanolic extract of leaves (FeLi), hexane fraction (FHLi) and dichloromethane fraction (FDLi), respectively and, β-sitosterol in FeLi (56.7 mg/100g DW), FHLi (10.55 g/100g DW), FDLi (106.1 mg/100g DW) and butanol fraction (FBLi) (357.4 mg/100g DW). Among the flavonoids, rutin = 3.24 g/100g and quercetin = 0.63 g/100g in the ethanolic extract, rutin = 15.73 g/100g in the dichloromethane fraction, and rutin = 0.23 g/100g) in the aqueous fraction;and among phenolic compounds, caffeic acid (37.65 g/100g DW) and vanillic acid (22.70 g/100g DW) were the most important in the ethyl acetate fraction (FAeLi). All organic fractions exhibited interesting antibacterial and antifungal activities against the tested strains, with the best activity recorded with the dichloromethane and ethyl acetate fractions. The leaf extracts’ phytochemical profile and antimicrobial activity support the use of Lawsonia inermis against infectious skin diseases.

Antimicrobial Activities of Extracts of Macrosphyra longistyla against Gram-Positive Oral Biofilm-Formers from School Children in Southwestern Nigeria and Toxicity Studies Using Brine Shrimps

The world will benefit from more effective antimicrobial agents against oral conditions arising from the actions of biofilm forming bacteria. Also, information is lacking on the oral biofilm-forming bacterial diversity in Southwestern Nigeria. In this study, we isolate and characterize oral biofilm producing bacteria in the oral cavities of schoolchildren in Southwestern Nigeria. We also investigate the antimicrobial properties of Macrosphyra longistyla extracts against the biofilm-formers and the toxicity of potent extracts. Samples were obtained from 109 schoolchildren aged 4 - 14 years from Lagos, Oyo and Osun States. Agar well diffusion technique was used in the antimicrobial susceptibility testing. Toxicity testing was done using brine shrimps (Artemia salina). Biofilm-formers in this study are Klebsiella sp., Streptococcus sp., Staphylococcus sp., and Micrococcus sp. Ethanol leaf extracts had the highest activity against all biofilm-producing bacteria. Ethanol stem bark extract, which elicited activity against Klebsiella only, was found to be less toxic than the ethanol leaf extract. Staphylococcus showed >10 mm susceptibility to the ethanol and aqueous extracts of Macrosphyra longistyla. Streptococcus and Micrococcus were susceptible to the antimicrobial actions of the ethanolic leaf extracts. Although the ethanol extracts of the leaves had lower minimum inhibitory concentrations than the ethanol extracts of the stem bark, toxicity studies showed ethanol extracts of the stem-bark to be more toxic than the ethanol extracts of the leaves. In conclusion, ethanolic extracts of Macrosphyra longistyla show potential as sources of antimicrobials against gram-positive, oral biofilm-forming bacteria.

Profile of Multidrug Resistant Bacteria in Bukavu Hospitals and Antimicrobial Susceptibility to Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Staphylococcus aureus

Objective: To evaluate the spread of Multidrug-Resistant (MDR) bacterial infections in Bukavu hospitals and test antimicrobial susceptibility patterns of some isolates to usual marketed antibiotics. Methods: The prevalence of MDR strains was determined by using general antimicrobial susceptibility data collected from 3 hospital laboratories. The susceptibility of some isolates to usual antibiotics was processed by agar diffusion method with standard E. coli ATCC8739 and standard antibiotics discs as controls. The tested antibiotics were ampicillin, ceftriaxone, gentamicin, chloramphenicol and ciprofloxacin. Results: At the 3 hospitals, 758 tests were realized in urine, pus, stool, FCV, blood, LCR, split and FU specimens;46 strains were unidentified and 712 strains were identified. Of 712 identified strains, 223 (31.4%) were MDR or XDR strains including Escherichia coli, Klebsiella pneumoniae, Enterobacter, Proteus mirabilis, Salmonella enterica, Pseudomonas aeruginosa, Citrobacter freundii, Morganella morganii, Enterococcus faecalis and E. faecium, Neisseria gonorrohoae, Staphylococcus aureus, coagulase-negative, staphylococci, Streptococcus pneumoniae and Streptococcus pyogenes. Of the infected patients, 36 (21.5%) children were under 16 years and 188 (78.5%) adults were predominately women (58.5%). The susceptibility test showed that all strains but S. aureus were resistant to ampicillin and amoxicillin and ciprofloxacin. Gentamicin, ceftriaxone, and chloramphenicol remain partially active (27% - 80%) against P. mirabilis, E. coli and P. aeruginosa. The resistance is more likely related to strain mutation than to pharmaceutical quality of the antibiotics prescribed. Conclusion: Both data from hospital laboratories and in vitro post-testing findings confirmed the ongoing elevated prevalence of MDR strains in Bukavu. The causes of antibiotic misuse and socio-economic determinants of the phenomenon of resistance should be scrutinized in order to take adequate strategies in the prospective of establishing an effective control system against this threat to overall health. The results of this work on MDR profiles have various implications for the management of infectious diseases. It provides indicators for the surveillance of antimicrobial resistance, practical guidelines for antibiotic susceptibility testing in biomedical laboratories, and guidance for antibiotic therapy.

Bacterial Exofactors Modulate Biofilm Growth and Resistivity to Antimicrobial Drugs

Some bacteria have the ability to co-exist, proliferate and survive in a multicellular community, biofilm. Each participating bacteria can form its colonies and encases itself by a self-produced insoluble extracellular matrix substance (EPS). Microcolonies within biofilm are held together by interactions and bonding of the substances present in the EPS with their separation from the water channels. Similar to insoluble EPS, bacterial microcolonies release soluble exofactors that have direct impacts on the survivability, growth and antibacterial resistivity of other microcolonies made of single- or multi-species bacteria in the same biofilm. How the exofactors of microcolonies of one-type bacteria impact on microcolonies of other-type bacteria is still unclear. We studied about the role of exofactors released from Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are common biofilm-forming pathogenic bacteria. Exofactors facilitate to transform the microenvironment where bacteria can acquire alternative lifestyle with a long survival period and resistivity to certain antimicrobial drugs.

Antimicrobial and Antioxidant Activities of a Brown Wood Rotting Mushroom Piptoporellus baudonii from Benin (Tropical Africa)

Piptoporellus baudonii, previously known as Laetiporus baudonii, is an African species that was considered to be a sister species to Laetiporus sulphureus, another European species known for its medicinal value. While much is known about the edibility and antimicrobial properties of L. sulphureus, African species like P. baudonii remain understudied. This study investigated the antimicrobial and antioxidant properties of P. baudonii extracts (powder maceration) prepared using ethanol, methanol and water with fractions obtained via differential solubility in hexane, ethyl acetate and n-butanol. Before the antimicrobial analysis, the study material was accurately identified using both morphology and molecular techniques. Antimicrobial activity was tested against fungi, gram-positive, and gram-negative bacteria using a broth serial microdilution method, while antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Power FRAP methods. Phylogenetic analysis confirmed the specimen as P. baudonii, with genetic material from Benin grouping it with other P. baudonii from Tanzania and other unknown regions, forming a well-supported clade (100/100). The ethanol (1.71), methanol (2.41) extracts, along with ethyl acetate (1.36), n-butanol (1.18), and hexane (12.91) fractions showed significant antioxidant activity with EC50 values below 20 µg∙mL−1. The highest antimicrobial inhibition was seen in the n-butanol (58%) and ethyl acetate (54%) fractions, followed by ethanol (49%) and hexane (48%). Methanol exhibited the lowest inhibition (46.10%). These values were compared to the standard (Vitamin C). The examined extracts demonstrated high bactericidal properties, with an MBC/MIC ratio (R) of 1 to 4, particularly effective ethyl acetate against Escherichia coli (R = 2) and ethanol extract with strong activity against Enterococcus faecalis (R = 4). Further chemical and cytotoxicity studies are warranted to fully explore the pharmaceutical potential of P. baudonii.

Impact of next-generation sequencing on antimicrobial treatment in immunocompromised adults with suspected infections

BACKGROUND:Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment.The objective of the study was to assess the diagnostic value of next-generation sequencing(NGS)for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections.METHODS:This was a retrospective study.Between January and August 2020,47 adult immunocompromised patients underwent NGS testing under the following clinical conditions:1)prolonged fever and negative conventional cultures;2)new-onset fever despite empiric antimicrobial treatment;and 3)afebrile with suspected infections on imaging.Clinical data,including conventional microbial test results and antimicrobial treatment before and after NGS,were collected.Data were analyzed according to documented changes in antimicrobial treatment(escalated,no change,or deescalated)after the NGS results.RESULTS:The median time from hospitalization to NGS sampling was 19 d.Clinically relevant pathogens were detected via NGS in 61.7% of patients(29/47),more than half of whom suffered from fungemia(n=17),resulting in an antimicrobial escalation in 53.2% of patients(25/47)and antimicrobial de-escalation in 0.2% of patients(1/47).Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella,Pneumocystis jirovecii,and Candida.In the remaining three cases,NGS detected clinically relevant pathogens also detected by conventional cultures a few days later.The antimicrobial treatment was subsequently adjusted according to the susceptibility test results.Overall,NGS changed antimicrobial management in 55.3%(26/47)of patients,and conventional culture detected clinically relevant pathogens in 14.9% of the patients(7/47).CONCLUSION:With its rapid identification and high sensitivity,NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.

Hydrolytic and Antimicrobial Activities of Bacteria Isolated from Fermented Peppers Sold in Markets at Brazzaville, Republic of the Congo

Microorganisms are omnipresent in all environments and play mainly the role of transformers, thanks to the multiple enzymes they are able to produce. In order to valorize fermented foods in the Republic of the Congo, this work aimed to characterize and study some properties of microorganisms isolated from samples of peppers sold in three markets of Brazzaville. A numeration of the total aerobic mesophilic flora (TAMF) was made in a solid medium, allowing the evaluation of each sample’s microbial concentration. The microbial mass varied from 2.8 × 105 CFU/g for the Ouénzé sample to 1.8 × 104 CFU/g for the Total sample and 2 × 104 CFU/g for the Moungali market sample. The evaluation of the enzymatic properties of the Bacillus isolates showed that 68.42% were capable of producing cellulases and 78.94% were capable of producing amylases and proteases. Antimicrobial activities revealed that 63.15% of the isolates were able to secrete inhibitory substances against E. coli and Staphylococcus aureus. Molecular analysis by PCR amplification, sequencing of the 16S rRNA gene and BLAST bioinformatics analysis provides newly identified bacteria strains with new accession numbers in GenBank: Bacillus thuringiensis MBCBR322 (OP474008), Bacillus megaterium MBCBJ1822 (OP476493), Bacillus thuringiensis MBCBR222 (OP476494), Priestia megaterium MBCBJ2022 (OP476495) and Lactobacillus paraplantarum MBCBR1522 (OP476496). Multiple sequences alignment of identified sequences with their homologs of GenBank has shown high similarities. The phylogenetic inference assay has provided the two groups of strains observed in this study, and the two groups are very coherent with the phylogeny of the reference.

Protective eff ect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection

BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae infections.Nanodefensin with a 14-carbon saturated fatty acid(ND-C14)is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of humanα-defensin 5(HD5)via an amide bond.However,it is unclear whether ND-C14 is effective against lung infections caused by S.pneumoniae.METHODS:In vitro,three groups were established,including the control group,and the HD5 and ND-C14 treatment groups.A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S.pneumoniae.The morphological changes of S.pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy.In vivo,mice were divided into sham,vehicle,and ND-C14 treatment groups.Mice in the sham group were treated with 25μL of phosphate-buffered saline(PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25μL of bacterial suspension with 2×108 CFU/mL(total bacterial count:5×10^(6) CFU),and then the mice were given 25μL PBS or intratracheally injected with 25μL of ND-C14(including 20μg or 50μg),respectively.Survival rates were evaluated in the vehicle and ND-C14 treatment groups.Bacterial burden in the blood and bronchoalveolar lavage fluid were counted.The lung histology of the mice was assessed.A propidium iodide uptake assay was used to clarify the destructive eff ect of ND-C14 against S.pneumoniae.RESULTS:Compared with HD5,ND-C14 had a better bactericidal eff ect against S.pneumoniae because of its stronger ability to destroy the membrane structure of S.pneumoniae in vitro.In vivo,ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S.pneumoniae.ND-C14 reduced bacterial burden and lung tissue injury.Moreover,ND-C14 had a membrane permeation eff ect on S.pneumoniae,and its destructive ability increased with increasing ND-C14 concentration.CONCLUSION:The ND-C14 may improve bactericidal eff ects on S.pneumoniae both in vitro and in vivo.

Bacteriological Profile, Antimicrobial Susceptibility Patterns and Predictors of Bacteremia in Neonates with Clinical Sepsis at KCMC Hospital, Northern Tanzania

Background: Despite a significant decline in neonatal deaths in the last 20 years (5 million in 1990 to 2.4 million in 2019), the risk of death is still high, especially in developing countries. In Tanzania, neonatal sepsis is the third leading cause of neonatal death, accounting for 25% of all deaths. The rising global threat of antimicrobial resistance and the rising burden of neonatal death due to neonatal sepsis have been of great concern and have delayed progress toward reaching SDG goal 3.2 by 2030. This study aims to determine the bacteriological profile, antibiotic susceptibility patterns, and predictors of bacteremia among neonates with clinical sepsis at KCMC Hospital in Northern Tanzania. Methodology: This study had a cross-sectional design conducted at KCMC Hospital, Northern Tanzania. The study population was neonates admitted to the neonatal unit at KCMC Hospital. Data were collected using questionnaires and blood cultures from neonates. Frequencies and proportions were used to summarize categorical variables, while continuous variables were summarized using mean and standard deviation. The frequencies and proportions of bacteria isolated and the antimicrobial susceptibility results were analyzed and compared using Pearson’s chi-square test and Fisher’s exact test where applicable. Modified Poisson regression model was used to determine factors associated with positive blood culture. Results: Out of 411 neonates with a clinical diagnosis of neonatal sepsis, 175 (42.9%) had positive blood cultures. Gram-positive bacteria were most frequently isolated at 52.3%, and gram-negative bacteria were 47.7%. Coagulase-negative Staphylococcus (30.7%) and Staphylococcus aureus (19.9%) were the predominant gram-positive isolates. Gram-negative isolates were Klebsiella spp 47 (26.7%), E. coli 10 (5.7%), and Citrobacter spp 10 (5.1%). The gram-positive isolates were sensitive to vancomycin, piperacillin/tazobactam, and ceftazidime, whereas the gram-negative were sensitive to amikacin, meropenem, and vancomycin. The study did not find statistically significant associations between clinical factors and positive blood cultures in bacteremia. Conclusion: Gram-positive bacteria are the dominant pathogens in early-onset and late-onset neonatal sepsis. High levels of resistance to ampicillin and ceftriaxone and moderate resistance to gentamycin were observed in both gram-positive and gram-negative bacteria. Gram-positive organisms exhibit better susceptibility rates to vancomycin and ciprofloxacin, while gram-negative micro-organisms are more sensitive to amikacin and meropenem. An effective initial treatment approach for neonatal sepsis would involve a combination of drugs.

Distribution of pathogenic bacteria and antimicrobial sensitivity of eye infections in Suzhou

AIM:To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs.METHODS:The clinical data of 155 patients were retrospectively collected in this study,and the pathogenic bacteria species and drug resistance of each pathogenic bacteria were analyzed.RESULTS:Among the 155 patients(age from 12 to 87 years old,with an average age of 57,99 males and 56 females)with eye infections(160 eyes:74 in the left eye,76 in the right eye and 5 in both eyes,all of which were exogenous),71(45.81%)strains were gram-positive bacteria,23(14.84%)strains were gram-negative bacteria and 61(39.35%)strains were fungi.Gram-positive bacteria were highly resistant to penicillin and erythromycin(78.87%and 46.48%respectively),but least resistant to vancomycin at 0.Gram-negative bacteria were highly resistant to cefoxitin and compound sulfamethoxazole(100%and 95.65%respectively),but least resistant to meropenem at 0.Comparison of the resistance of gram-positive and gram-negative bacteria to some drugs revealed statistically significant differences(P<0.05)in the resistance of both to cefoxitin,cotrimoxazole,levofloxacin,cefuroxime,ceftriaxone and ceftazidime,and both had higher rates of resistance to gram-negative bacteria than to gram-positive bacteria.The distribution of bacterial infection strains showed that Staphylococcus epidermidis was the most common strain in the conjunctiva,cornea,aqueous humor or vitreous body and other eye parts.Besides,Fusarium and Pseudomonas aeruginosa were also among the most common strains of conjunctival and corneal infections.CONCLUSION:Gram-positive bacteria are the dominant bacteria in eye infections,followed by gram-negative bacteria and fungi.Considering the resistance of gramnegative bacteria to multiple drugs,monitoring of bacteria should be strengthened in eye bacterial infections for effective prevention and control to reduce complications caused by eye infections.

Design of pH-responsive antimicrobial peptide melittin analog-camptothecin conjugates for tumor therapy

Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with histidine.After conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions.Notably,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus.CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity.Collectively,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.

Electrospun polyvinyl alcohol fibres incorporating an antimicrobial gel for enzymatically controlled reactive oxygen species release

Wounds pose a risk to the skin,our body's primary defence against infections.The rise of antibiotic resistance has prompted the development of novel therapies.RO-101^(■)is an antimicrobial gel that delivers therapeutic levels of hydrogen peroxide(H_(2)O_(2)),a reactive oxygen species,directly to the wound bed.In this study,electrospinning was used to incorporate RO-101^(■)into a polyvinyl alcohol(PVA)sub-micron fibrous mesh that can act as a delivery agent,achieve a sustained release profile,and provide a barrier against infection.Adequate incorporation of this gel into sub-micron fibres was confirmed via nuclear magnetic resonance spectroscopy.Furthermore,scanning electron microscopy exhibited smooth and uniform meshes with diameters in the 200-500 nm range.PVA/RO-101 electrospun meshes generated H_(2)O_(2) in concentrations exceeding 1 m M/(g·m L)(1 m M=1 mmol/L)after 24 h,and the role of sterilisation on H_(2)O_(2) release was evaluated.PVA/RO-101meshes exhibited antimicrobial activity against both Gram-positive Staphylococcus aureus(S.aureus)and Gram-negative Pseudomonas aeruginosa(P.aeruginosa)bacteria,achieving viable count reductions of up to 1 log unit CFU/mm^(2)(CFU:colony-forming units).Moreover,these meshes were capable of disrupting biofilm formation,even against multidrug-resistant organisms such as methicillin-resistant S.aureus(MRSA).Furthermore,increasing the RO-101^(■)concentration resulted in higher H_(2)O_(2) production and an enhanced antimicrobial effect,while fibroblast cell viability and proliferation tests showed a concentration-dependent response with high cytocompatibility at low RO-101^(■)concentrations.This study therefore demonstrates the potential of highly absorbent PVA/RO-101 meshes as potential antimicrobial wound dressings.

Corrosion and antimicrobial property of TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)micro-arc oxidation coatings on Ti-6Al-4V alloys in natural seawater

Microarc oxidation is an effective surface treatment for improving certain properties of metals and their alloys.In this paper,TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)coatings were prepared on Ti-6Al-4V by microarc oxidation.Thecoatings exhibited good corrosion resistance and antimicrobial properties.X-ray diffraction(XRD),scanning electronmicroscopy(SEM),and 3D laser confocal were used to characterize the coatings.The properties of TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)coatings were analyzed,including microstructure,surface roughness,corrosion resistance,andantimicrobial properties.The electrochemical results showed that the coatings prepared by microarc oxidation hadenhanced corrosion resistance compared to the substrate.The antibacterial properties of TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)coating against Pseudomonas aeruginosa were evaluated by fluorescence microscopy and plate counting.The antibacterial rate of TiO_(2)/Cu_(2)O@CeO_(2)coating was up to 99.70%.In summary,the TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)coatings prepared by microarc oxidation have a potential application background in the field of marine corrosionprotection and biofouling.

Antioxidant,antimicrobial,and anticancer effects of Achillea filipendulina L.against colon cancer

Objective:To investigate the antioxidant,antimicrobial,and anticancer effects of Achillea filipendulina.Methods:Phytochemical content was analyzed by GC-MS.Antioxidant activity was assayed by DPPH,total antioxidant status,total oxidant status,and iron reduction tests.Antimicrobial activity was assessed using the MIC assay.Anticancer activity was detected via MTT assay,followed by analysis of the apoptotic process using annexin V and caspase 3/7.miR-519d and Dvl-1 expression were assessed by RT-PCR,and molecular docking analysis was also performed.Results:The ethanol extract of Achillea filipendulina showed the strongest anticancer effect.A significant increase in miR-519d expression was observed in HT29 cells,while a decrease in Dvl-1 expression was noted.DPPH,FRAP,total antioxidant status,and total oxidant assays showed high antioxidant activity.The hexane and ethanol extracts were effective against Streptococcus mutans(MIC<50μg/mL),while the ethanol extract was effective against Enterococcus faecalis and Candida albicans(MIC<50μg/mL).Molecular docking studies also confirmed that ethanol extracts could act on the Wnt pathway.GC-MS analysis showed high level of eucalyptol and borneol content in the extract.Conclusions:Ethanol extract of Achillea filipendulina has anticancer effect and can be used in colon cancer treatments.

Effect of weight-adjusted antimicrobial antibiotic prophylaxis on postoperative dosage and surgical site infection incidence in total joint arthroplasty

Surgical site infections(SSI)following total joint arthroplasty pose a significant concern for both providers and patients across the globe.Currently,administration of antimicrobial antibiotic prophylaxis is used throughout the world to reduce the incidence of SSI.However,the correct dosage and frequency of administration remains debatable.In this editorial,we emphasized the determination of the effect of administration of weight-adjusted antimicrobial antibiotic prophylaxis regime on the incidence of SSI and postoperative dosage reduction compared to the conventionally used regime during total joint arthroplasty.The results demonstrated similar efficacy between both regimes with respect to the incidence of SSI.In addition,weight-adjustment led to reduced postoperative dosage and has the potential to reduce chances of achieving lower therapeutic concentration,drug resistance,drug toxicity,and costs.

Research Progress of Antimicrobial Peptides and the Potential Applications of Bacillus subtilis

This paper presents a comprehensive account of antimicrobial peptides (AMPs) derived from various sources, including animal, plant, and microbial origins, along with an examination of their structural characteristics and biological activities. Specifically, the potential of Bacillus subtilis as a safe and effective host for the production of AMPs is discussed. B. subtilis exhibits a notable capacity for protein secretion and is also capable of efficiently producing AMPs without the presence of endotoxin contamination. The research indicates that the production efficiency of AMPs derived from B. subtilis can be significantly enhanced through the application of genetic engineering and synthetic biology techniques. This advancement holds considerable potential for applications in food preservation, agriculture, medicine, and various other fields. The paper additionally investigates the stability of AMPs under diverse conditions of temperature, pH, and enzymatic treatment, and highlights the necessity for further research to facilitate the advancement of these AMPs for practical applications.

Antimicrobial Activity, Structural, Crystallographic and Thermal Characteristics of Alpha-Titanium Phosphate Promoted by Silver Ions

The recent global spread of the pandemic underscores the necessity of seeking new materials effective against microorganisms. Nanotechnology offers avenues for developing multifunctional materials. In this study, alpha-titanium phosphate (α-TiP) nanoparticles were synthesized and treated with silver salt to enhance their antimicrobial properties. The physicochemical characteristics and antimicrobial activity were evaluated. It was revealed by X-ray diffraction analysis that the structural integrity of α-TiP was influenced by ethylenediamine and silver ions. Distinct degradation profiles for each chemical modification were shown by thermogravimetric analysis. Infrared spectroscopy detected shifts and new absorption peaks in the spectra depending on the type of modification. Energy dispersive spectroscopy confirmed the disaggregation of α-TiP galleries following the addition of silver salt, which increased their effectiveness against microorganisms. Notably, only the sample treated with silver ions exhibited antimicrobial action. Antimicrobial activity was tested against the bacteria of medical importance Escherichia coli, Salmonella Enteritidis, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus, Listeria momocytogenes and the yeast Candida albicans. All microorganisms were inhibited by sample containing silver. Minor inhibition was observed against the Gram-positive bacteria L. monocytogenes and Bacillus cereus, while the greatest inhibition occurred against the fungus (yeast) C. albicans. The results revealed a potential application of the nanoparticles for control of microorganisms in public health.