BACKGROUND Helicobacter pylori(H.pylori)is the most common chronic bacterial infection in humans.The risk of acquiring H.pylori is related to socioeconomic status and living conditions early in life.Treatment regimens...BACKGROUND Helicobacter pylori(H.pylori)is the most common chronic bacterial infection in humans.The risk of acquiring H.pylori is related to socioeconomic status and living conditions early in life.Treatment regimens must consider local antibiotic resistance patterns.Adventist Health White Memorial Hospital serves a predominantly indigent population in east Los Angeles with a large number of immigrants from South and Central America.Data regarding the prevalence and resistance of H.pylori in this population is scant.AIM To evaluate the prevalence and resistance of H.pylori and correlate with country of origin.METHODS All gastric biopsies were obtained by a single gastroenterologist at the hospital in a consecutive manner from patients with gastritis from 2017 to 2022 and sent to various labs for evaluation.RESULTS Two hundred and sixty-six patients are born in the United States,450,171,70,and 30 patients are immigrants from Mexico,Central and South America(CSA),Asia,and other countries respectively.Overall,14.65%were found to be infected with H.pylori.Rates of infection in United States-born citizens,immigrants from Mexico,CSA,and Asia are 9.02%,18.67%,13.45%,and 11.43%respectively,with Mexican immigrants having a relative risk of 2.3889[95%confidence interval(CI):1.4789-3.8588,P=0.0004]compared to those born in United States.No correlation seen between infection and length of time immigrants were in United States.Relative risk of infection in patients with no proton pump inhibitor use within the past 30 days found to be 1.9276(95%CI:1.3562-2.7398,P=0.0003).Rates of resistance for clarithromycin and levofloxacin are 21.43%and 31.11%.CONCLUSION H.pylori infection appears to be associated with low socioeconomic status and poor living conditions early in life.Clarithromycin and levofloxacin based treatment regimens should be avoided as first line therapy in this region,particularly in patients of Latin American origin.展开更多
AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's...AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's blood. The multidrug resistant (MDR) H. pylori were obtained with the inducer chloramphenicol by repeated doubling of the concentration until no colony was seen, then the susceptibilities of the MDR strains and their parents to 9 antibiotics were assessed with agar dilution tests. The present study included periods before and after the advent of the EPIs, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), reserpine and pantoprazole), and the minimum inhibitory concentrations (MICs) were determined accordingly. In the same way, the effects of 5 proton pump inhibitors (PPIs), used in treatment of H. pylori infection, on MICs of antibiotics were evaluated.RESULTS: Four strains of MDR H. pylori were induced successfully, and the antibiotic susceptibilities of MDR strains were partly restored by CCCP and pantoprazole, but there was little effect of reserpine. Rabeprazole was the most effective of the 5 PPIs which could decrease the MICs of antibiotics for MDR H. pylori significantly.CONCLUSION: In vitro, some EPIs can strengthen the activities of different antibiotics which are the putative substrates of the efflux pump system in H. pylori.展开更多
AIM: To determine whether efflux systems contribute to multidrug resistance of H pylori. METHODS: A chloramphenicol-induced multidrug resistance model of six susceptible H pylori strains (5 isolates and H pylori NCTC1...AIM: To determine whether efflux systems contribute to multidrug resistance of H pylori. METHODS: A chloramphenicol-induced multidrug resistance model of six susceptible H pylori strains (5 isolates and H pylori NCTC11637) was developed. Multidrug-resistant (MDR) strains were selected and the minimal inhibitory concentration (MIC) of eryth-romycin, metronidazole, penicillin G, tetracycline, and ciprofloxacin in multidrug resistant strains and their parent strains was determined by agar dilution tests. The level of mRNA expression of hefA was assessed by fluorescence real-time quantitative PCR. A H pylori LZ1026 knockout mutant (ΔH pylori LZ1026) for (puta-tive) efflux protein was constructed by inserting the kanamycin resistance cassette from pEGFP-N2 into hefA, and its susceptibility profiles to 10 antibiotics were evaluated. RESULTS: The MIC of six multidrug-resistant strains (including 5 clinical isolates and H pylori NCTC11637) increased signifi cantly (≥ 4-fold) compared with their parent strains. The expression level of hefA gene was significantly higher in the MDR strains than in their parent strains (P = 0.033). A H pylori LZ1026 mutant was successfully constructed and the ΔH pylori LZ1026 was more susceptible to four of the 10 antibiotics. All the 20 strains displayed transcripts for hefA that con-fi rmed the in vitro expression of these genes.CONCLUSION: The efflux pump gene hefA plays an important role in multidrug resistance of H pylori.展开更多
Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Teh...Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Tehran, Iran. Methods: In this cross-sectional descriptive study, 100 strains of A. baumannii isolated from burn patients visiting teaching hospitals of Tehran were collected from January 2016 to November 2017. After A. baumannii strains were confirmed, antimicrobial susceptibility testing was done via Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute guidelines. PCR amplification was performed for detection of β-lactamase adeR, OprD, adeS genes among A. baumannii strains. Results: All isolates (100%) were resistant to ceftazidime, cefotaxime, cefepime, ciprofloxacin, and piperacillin, and most isolates indicated high resistance (95%-97%) to meropenem, imipenem, gentamicin, ceftriaxone, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, amikacin, and tetracycline. The most effective antibiotic against A. baumannii isolates was colistin (97% sensitivity), followed by tigecycline. The frequency of OprD, adeS, and adeR genes were 98%, 91%, and 77%, respectively. Conclusions: This study shows that the majority of A. baumannii isolates are highly resistant to the antibiotics most commonly used in burn patients. Also, high distribution of OprD and adeRS genes may be responsible for the observed resistances among A. baumannii isolates that demonstrate the possible role of both efflux pumps in simultaneous of carbapenemase production during antibiotic resistance.展开更多
Acinetobacter baumannii has greatly increased its degree of resistance to become multidrug resistant (MDR) over the past 30 years and is on the red line of the most widely replicated bacteria according to World Health...Acinetobacter baumannii has greatly increased its degree of resistance to become multidrug resistant (MDR) over the past 30 years and is on the red line of the most widely replicated bacteria according to World Health Organization (WHO). The efflux pumps are the main cause for the increasing antibiotic resistance of A. baumannii originated from nosocomial infection. The progressive resistance of A. baumannii even on the recent drugs (tigecycline and fosfomycin) reduces to very effective antibiotic scale. With attention focused on MDR and pan-drug-resistant (PDR) in A. baumannii multiple works on efflux pumps chemical inhibitor (NMP, PAβN, omeprazole, verapamil, reserpine, CCCP) are still in progress. Certain inhibitors from plants (Biricodar and timcodar, Falvone, Mahonia, Dalea versicolor, Lycopus europaeus, and Rosmarinus officinalis) have the capability to have such compounds according to their very significant synergistic effect with antibiotics. In this review we focused on the growth of antibiotic resistance to explain the mechanism of efflux pumps into these different super families and a comprehensive understanding of the extrusion, regulation and physiology role of drug efflux pumps in the essential development of anti-resistivity drugs. We recapitulated the evolution of the work carried out in these fields during the last years and in the course of elaboration, with the aim of increasing the chances of decreasing bacterial resistivity to antibiotics.展开更多
Based on nuclear power plant(NPP) best-estimate transient analysis with RELAP5 / MOD3 code,the reactor point kinetics model in RELAP5 / MOD3 code is replaced by the two-group,3-D space and time dependent neutron kinet...Based on nuclear power plant(NPP) best-estimate transient analysis with RELAP5 / MOD3 code,the reactor point kinetics model in RELAP5 / MOD3 code is replaced by the two-group,3-D space and time dependent neutron kinetic model,and two-fluid model is replaced by drift flux model.A coupled three-dimensional physics and thermal-hydrodynamics model is used to develop its corresponding computing code,thus simulating natural circulation of single-phase flow for the PWR.In this paper,we report the forward and reverse flow distribution in the inverted U-tubes of the steam generator(SG) under some typical operating conditions in the natural circulation case, and analyze the influence of main coolant pump resistance on the forward and reverse flow distribution.The calculation results show that,the pressure drop between SG inlet and outlet plenum decreases,and the SG inlet and outlet mass flow decrease with an increased main coolant pump resistance,but net mass flux of reverse flow in inverted U-tubes,and the ratio of mass flow in all reverse flow tubes to that of main coolant pipeline increase, meanwhile,the secondary steam load is invariable in this process.展开更多
The aim of this study was to detect the expression of 4 clinically-important efflux pumps in the Resistance-Nodulation-Cell Division (RND) family including MexAB-OprM, MexXY, MexCD-OprJ and MexEF-OprN in Pseudomonas a...The aim of this study was to detect the expression of 4 clinically-important efflux pumps in the Resistance-Nodulation-Cell Division (RND) family including MexAB-OprM, MexXY, MexCD-OprJ and MexEF-OprN in Pseudomonas aeruginosa using a combination of resistance-phenotypic markers and multiplex RT-PCR (mRT-PCR). The antibiotic substrates specific for each Mex systems were used as phenotypic markers including carbenicillin, MexAB-OprM, erythromycin, MexCD-OprJ, norfloxacin and imipenem, MexEF-OprN and gentamicin, MexXY-OprM. The methods were validated with reference strains with known genotypes of the Mex systems and the potential applicability in clinical practice was tested with clinical isolates. The results for the reference strains support that the combination of resistance phenotype and mRT-PCR is a potential-attractive method for diagnosis of efflux-mediated resistance in P. aeruginosa. Further development to make it more practical for clinical use and study in a larger number of clinical isolates is required.展开更多
Objective Mutations in 23 S rRNA gene are known to be associated with macrolide resistance in Mycoplasma pneumoniae(M. pneumoniae). However, these mutations alone do not fully explain the high resistance rates in As...Objective Mutations in 23 S rRNA gene are known to be associated with macrolide resistance in Mycoplasma pneumoniae(M. pneumoniae). However, these mutations alone do not fully explain the high resistance rates in Asia. The aim of this study was to investigate other possible mutations involved in macrolide resistance in M. pneumoniae. Methods The whole genomes of 10 clinical isolates of M. pneumoniae with macrolide resistance were sequenced by Illumina Hi Seq2000 platform. The role of the macrolide-specific efflux transporter was assessed by efflux-pump inhibition assays with reserpine and carbonyl cyanide m-chlorophenyl-hydrazone(CCCP). Results A total of 56 single nucleotide polymorphisms(SNPs) were identified in 10 clinical isolates in comparison to the reference strains M129 and FH. Strikingly, 4 of 30 SNPs causing non-synonymous mutations were clustered in macrolide-specific efflux system gene mac B encoding macrolide-specific efflux pump protein of the ATP-binding cassette transporter family. In assays of the minimal inhibitory concentrations(MIC) of macrolide antibiotics in the presence of the efflux pump inhibitors caused a significant decrease of MICs, even under detectable levels in some strains. Conclusion Our study suggests that macrolide efflux pump may contribute to macrolide resistance in M. pneumoniae in addition to the common point mutations in 23 S r RNA gene.展开更多
A biofilm refers to a group of organized bacteria attached to the surface of living or inanimate objects and surrounded by some macromolecules. It is rich in organic components such as polysaccharides,peptides and pho...A biofilm refers to a group of organized bacteria attached to the surface of living or inanimate objects and surrounded by some macromolecules. It is rich in organic components such as polysaccharides,peptides and phospholipids,greatly increases the resistance of bacteria to antibacterial drugs,and can cause infections in humans and animals. At present,the measure to prevent the infections is to prevent microbial colonies from adhering to the surface of the objects,which will help to improve the therapeutic effect of clinically serious infectious diseases. In addition,the identification and inhibition of biofilm formation genes is also an important research direction to control such infections. In this paper,molecular mechanisms of bacterial biofilm resistance to drugs that has caused widespread concern were summarized.展开更多
Bacterial resistance to antibiotics is an increasing threat to global healthcare systems.We therefore sought compounds with potential to reverse antibiotic resistance in a clinically relevant multi-drug resistant isol...Bacterial resistance to antibiotics is an increasing threat to global healthcare systems.We therefore sought compounds with potential to reverse antibiotic resistance in a clinically relevant multi-drug resistant isolate of Escherichia coli(NCTC 13400).200 natural compounds with a history of either safe oral use in man,or as a component of a traditional herb or medicine,were screened.Four compounds;ellagic acid,propyl gallate,cinchonidine and cepharanthine,lowered the minimum inhibi-tory concentrations(MICs)of tetracycline,chloramphenicol and tobramycin by up to fourfold,and when combined up to eightfold.These compounds had no impact on the MICs of ampicillin,erythromycin or trimethoprim.Mechanistic studies revealed that while cepharanthine potently suppressed efflux of the marker Nile red from bacterial cells,the other hit com-pounds slowed cellular accumulation of this marker,and/or slowed bacterial growth in the absence of antibiotic.Although cepharanthine showed some toxicity in a cultured HEK-293 mammalian cell-line model,the other hit compounds exhibited no toxicity at concentrations where they are active against E.coli NCTC 13400.The results suggest that phytochemicals with capacity to reverse antibiotic resistance may be more common in traditional medicines than previously appreciated,and may offer useful scaffolds for the development of antibiotic-sensitising drugs.展开更多
Salmonella gallinarum has shown multiple drug resistance(MDR),especially high level fluoroquinolone(FQ)resistance in recent years.To determine whether the active efflux system was responsible for high-level FQ resista...Salmonella gallinarum has shown multiple drug resistance(MDR),especially high level fluoroquinolone(FQ)resistance in recent years.To determine whether the active efflux system was responsible for high-level FQ resistance,this research studied AcrAB efflux pump in Salmonella gallinarum on molecular level.The resistant strains were induced by standard strain C79-13 with ciprofloxacin in vitro.With carbonylcyanide-p-chlorophenyl hydrazone(CCCP)as an energy inhibitor,efflux inhibition test initially showed the potential impact of efflux pump on drug resistance.Sequence analysis of acrA gene indicated that gene mutation of AcrAB efflux pump was not definitely associated with MDR and drug resistance level of Salmonella gallinarum.Detected by competitive RT-PCR,the mRNA expression of acrA and acrB genes in the resistant strains significantly increased(p<0.01)compared with that of the control strain C79-13.The mRNA expression level of acrB gene(increased from 1.6-to 2.9-folds)was consistent with that of acrA gene(increased from 1.6-to 2.8-folds),which increased with the drug resistance level.However,gene mutation of acrA gene showed no correlation with its mRNA expression level,indicating that gene mutation did not affect the expression of AcrAB pump itself.The results suggested that the overexpression rather than the gene mutation of AcrAB efflux pump was an important factor causing the high level drug resistance of Salmonella gallinarum.展开更多
The present study focused on MexCD-OprJ efflux pump and its regulatory gene nfxB in multidrug resistant (MDR) clinical isolates of Pseudomonas aeruginosa collected from Kerala, South India. Semi-quantitative reverse t...The present study focused on MexCD-OprJ efflux pump and its regulatory gene nfxB in multidrug resistant (MDR) clinical isolates of Pseudomonas aeruginosa collected from Kerala, South India. Semi-quantitative reverse transcription-PCR technique was employed to detect hyperexpression of the efflux pump gene, mexD. Amplicons from nfxB gene of isolates hyperexpressing the efflux pump were sequenced for mutational and phylogenetic analysis. Among 29 isolates of MDR P. aeruginosa, increased mexD transcription was detected in 10.3% of the isolates when compared with P. aeruginosa reference strain, PAO (MTCC-3541). Various synonymous and non-synonymous mutations in nfxB regulatory gene sequences were detected. Notably, mutations detected in the strains designate Pa6 and Pa7 have been found to be novel and are hitherto unreported in GenBank data base. The genetic divergence and homogeneity of the nfxB regulatory gene sequences of mexCD-oprJ operon were clearly apparent in the phylogram generated employing similar sequences retrieved from the public database.展开更多
Purpose: Myocardial revascularization by coronary artery bypass grafting (CABG) in ischemic heart disease patients has direct impact on hemodynamic parameters in the immediate post-operative period. The peri-operative...Purpose: Myocardial revascularization by coronary artery bypass grafting (CABG) in ischemic heart disease patients has direct impact on hemodynamic parameters in the immediate post-operative period. The peri-operative cardiovascular functioning is an important determinant for outcome of surgery. In On-Pump CABG (ONCAB), the cardiopulmonary bypass has a negative effect on myocardium. Off-Pump CABG (OPCAB) avoids the effect of CPB but complete revascularization with difficult positioning of heart is technically demanding. This study is aimed to compare the cardiovascular functioning in the immediate post-operative period after OPCAB and ONCAB. Methods: Total 106 patients were operated for CABG from January 2015 to June 2016, of which 75 patients were operated for OPCAB and 31 patients were operated for ONCAB. For the comparison, hemodynamic parameters were measured during anesthesia before surgery, postoperatively after 1 and 4 hours (h) in the ICU, and in the morning after surgery, approximately after 20 h. Results: The time-dependent rise of hemodynamic parameters like Cardiac Output (CO), Cardiac Index (CI), Stroke volume (SV) and Left Ventricular Stroke Work Index (LVSWI) in the immediate post-operative hours (1 h and 4 h) are more predominant in OPCAB group than ONCAB group although the difference is eliminated mostly at 20 h. The better peripheral vasodilation after OPCAB causes immediate fall of Systemic Vascular Resistance Index (SVRI) after OPCAB. Conclusion: Better cardiovascular functioning immediately after OPCAB than ONCAB may be important for better hemodynamic stability. The difference is however eliminated after 24 hours indicating little significance in long term outcome.展开更多
文摘BACKGROUND Helicobacter pylori(H.pylori)is the most common chronic bacterial infection in humans.The risk of acquiring H.pylori is related to socioeconomic status and living conditions early in life.Treatment regimens must consider local antibiotic resistance patterns.Adventist Health White Memorial Hospital serves a predominantly indigent population in east Los Angeles with a large number of immigrants from South and Central America.Data regarding the prevalence and resistance of H.pylori in this population is scant.AIM To evaluate the prevalence and resistance of H.pylori and correlate with country of origin.METHODS All gastric biopsies were obtained by a single gastroenterologist at the hospital in a consecutive manner from patients with gastritis from 2017 to 2022 and sent to various labs for evaluation.RESULTS Two hundred and sixty-six patients are born in the United States,450,171,70,and 30 patients are immigrants from Mexico,Central and South America(CSA),Asia,and other countries respectively.Overall,14.65%were found to be infected with H.pylori.Rates of infection in United States-born citizens,immigrants from Mexico,CSA,and Asia are 9.02%,18.67%,13.45%,and 11.43%respectively,with Mexican immigrants having a relative risk of 2.3889[95%confidence interval(CI):1.4789-3.8588,P=0.0004]compared to those born in United States.No correlation seen between infection and length of time immigrants were in United States.Relative risk of infection in patients with no proton pump inhibitor use within the past 30 days found to be 1.9276(95%CI:1.3562-2.7398,P=0.0003).Rates of resistance for clarithromycin and levofloxacin are 21.43%and 31.11%.CONCLUSION H.pylori infection appears to be associated with low socioeconomic status and poor living conditions early in life.Clarithromycin and levofloxacin based treatment regimens should be avoided as first line therapy in this region,particularly in patients of Latin American origin.
基金Supported by Henan Distinguished Junior Scholar Grant,No.074100510017
文摘AIM:To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori).METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep's blood. The multidrug resistant (MDR) H. pylori were obtained with the inducer chloramphenicol by repeated doubling of the concentration until no colony was seen, then the susceptibilities of the MDR strains and their parents to 9 antibiotics were assessed with agar dilution tests. The present study included periods before and after the advent of the EPIs, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), reserpine and pantoprazole), and the minimum inhibitory concentrations (MICs) were determined accordingly. In the same way, the effects of 5 proton pump inhibitors (PPIs), used in treatment of H. pylori infection, on MICs of antibiotics were evaluated.RESULTS: Four strains of MDR H. pylori were induced successfully, and the antibiotic susceptibilities of MDR strains were partly restored by CCCP and pantoprazole, but there was little effect of reserpine. Rabeprazole was the most effective of the 5 PPIs which could decrease the MICs of antibiotics for MDR H. pylori significantly.CONCLUSION: In vitro, some EPIs can strengthen the activities of different antibiotics which are the putative substrates of the efflux pump system in H. pylori.
文摘AIM: To determine whether efflux systems contribute to multidrug resistance of H pylori. METHODS: A chloramphenicol-induced multidrug resistance model of six susceptible H pylori strains (5 isolates and H pylori NCTC11637) was developed. Multidrug-resistant (MDR) strains were selected and the minimal inhibitory concentration (MIC) of eryth-romycin, metronidazole, penicillin G, tetracycline, and ciprofloxacin in multidrug resistant strains and their parent strains was determined by agar dilution tests. The level of mRNA expression of hefA was assessed by fluorescence real-time quantitative PCR. A H pylori LZ1026 knockout mutant (ΔH pylori LZ1026) for (puta-tive) efflux protein was constructed by inserting the kanamycin resistance cassette from pEGFP-N2 into hefA, and its susceptibility profiles to 10 antibiotics were evaluated. RESULTS: The MIC of six multidrug-resistant strains (including 5 clinical isolates and H pylori NCTC11637) increased signifi cantly (≥ 4-fold) compared with their parent strains. The expression level of hefA gene was significantly higher in the MDR strains than in their parent strains (P = 0.033). A H pylori LZ1026 mutant was successfully constructed and the ΔH pylori LZ1026 was more susceptible to four of the 10 antibiotics. All the 20 strains displayed transcripts for hefA that con-fi rmed the in vitro expression of these genes.CONCLUSION: The efflux pump gene hefA plays an important role in multidrug resistance of H pylori.
文摘Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Tehran, Iran. Methods: In this cross-sectional descriptive study, 100 strains of A. baumannii isolated from burn patients visiting teaching hospitals of Tehran were collected from January 2016 to November 2017. After A. baumannii strains were confirmed, antimicrobial susceptibility testing was done via Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute guidelines. PCR amplification was performed for detection of β-lactamase adeR, OprD, adeS genes among A. baumannii strains. Results: All isolates (100%) were resistant to ceftazidime, cefotaxime, cefepime, ciprofloxacin, and piperacillin, and most isolates indicated high resistance (95%-97%) to meropenem, imipenem, gentamicin, ceftriaxone, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, amikacin, and tetracycline. The most effective antibiotic against A. baumannii isolates was colistin (97% sensitivity), followed by tigecycline. The frequency of OprD, adeS, and adeR genes were 98%, 91%, and 77%, respectively. Conclusions: This study shows that the majority of A. baumannii isolates are highly resistant to the antibiotics most commonly used in burn patients. Also, high distribution of OprD and adeRS genes may be responsible for the observed resistances among A. baumannii isolates that demonstrate the possible role of both efflux pumps in simultaneous of carbapenemase production during antibiotic resistance.
文摘Acinetobacter baumannii has greatly increased its degree of resistance to become multidrug resistant (MDR) over the past 30 years and is on the red line of the most widely replicated bacteria according to World Health Organization (WHO). The efflux pumps are the main cause for the increasing antibiotic resistance of A. baumannii originated from nosocomial infection. The progressive resistance of A. baumannii even on the recent drugs (tigecycline and fosfomycin) reduces to very effective antibiotic scale. With attention focused on MDR and pan-drug-resistant (PDR) in A. baumannii multiple works on efflux pumps chemical inhibitor (NMP, PAβN, omeprazole, verapamil, reserpine, CCCP) are still in progress. Certain inhibitors from plants (Biricodar and timcodar, Falvone, Mahonia, Dalea versicolor, Lycopus europaeus, and Rosmarinus officinalis) have the capability to have such compounds according to their very significant synergistic effect with antibiotics. In this review we focused on the growth of antibiotic resistance to explain the mechanism of efflux pumps into these different super families and a comprehensive understanding of the extrusion, regulation and physiology role of drug efflux pumps in the essential development of anti-resistivity drugs. We recapitulated the evolution of the work carried out in these fields during the last years and in the course of elaboration, with the aim of increasing the chances of decreasing bacterial resistivity to antibiotics.
文摘Based on nuclear power plant(NPP) best-estimate transient analysis with RELAP5 / MOD3 code,the reactor point kinetics model in RELAP5 / MOD3 code is replaced by the two-group,3-D space and time dependent neutron kinetic model,and two-fluid model is replaced by drift flux model.A coupled three-dimensional physics and thermal-hydrodynamics model is used to develop its corresponding computing code,thus simulating natural circulation of single-phase flow for the PWR.In this paper,we report the forward and reverse flow distribution in the inverted U-tubes of the steam generator(SG) under some typical operating conditions in the natural circulation case, and analyze the influence of main coolant pump resistance on the forward and reverse flow distribution.The calculation results show that,the pressure drop between SG inlet and outlet plenum decreases,and the SG inlet and outlet mass flow decrease with an increased main coolant pump resistance,but net mass flux of reverse flow in inverted U-tubes,and the ratio of mass flow in all reverse flow tubes to that of main coolant pipeline increase, meanwhile,the secondary steam load is invariable in this process.
文摘The aim of this study was to detect the expression of 4 clinically-important efflux pumps in the Resistance-Nodulation-Cell Division (RND) family including MexAB-OprM, MexXY, MexCD-OprJ and MexEF-OprN in Pseudomonas aeruginosa using a combination of resistance-phenotypic markers and multiplex RT-PCR (mRT-PCR). The antibiotic substrates specific for each Mex systems were used as phenotypic markers including carbenicillin, MexAB-OprM, erythromycin, MexCD-OprJ, norfloxacin and imipenem, MexEF-OprN and gentamicin, MexXY-OprM. The methods were validated with reference strains with known genotypes of the Mex systems and the potential applicability in clinical practice was tested with clinical isolates. The results for the reference strains support that the combination of resistance phenotype and mRT-PCR is a potential-attractive method for diagnosis of efflux-mediated resistance in P. aeruginosa. Further development to make it more practical for clinical use and study in a larger number of clinical isolates is required.
基金supported by the grants from National Nature Science Foundation of China(81601778 and 81672062)the Beijing Natural Science Foundation(7152025)Beijing Talents Fund(2015000021469G192)
文摘Objective Mutations in 23 S rRNA gene are known to be associated with macrolide resistance in Mycoplasma pneumoniae(M. pneumoniae). However, these mutations alone do not fully explain the high resistance rates in Asia. The aim of this study was to investigate other possible mutations involved in macrolide resistance in M. pneumoniae. Methods The whole genomes of 10 clinical isolates of M. pneumoniae with macrolide resistance were sequenced by Illumina Hi Seq2000 platform. The role of the macrolide-specific efflux transporter was assessed by efflux-pump inhibition assays with reserpine and carbonyl cyanide m-chlorophenyl-hydrazone(CCCP). Results A total of 56 single nucleotide polymorphisms(SNPs) were identified in 10 clinical isolates in comparison to the reference strains M129 and FH. Strikingly, 4 of 30 SNPs causing non-synonymous mutations were clustered in macrolide-specific efflux system gene mac B encoding macrolide-specific efflux pump protein of the ATP-binding cassette transporter family. In assays of the minimal inhibitory concentrations(MIC) of macrolide antibiotics in the presence of the efflux pump inhibitors caused a significant decrease of MICs, even under detectable levels in some strains. Conclusion Our study suggests that macrolide efflux pump may contribute to macrolide resistance in M. pneumoniae in addition to the common point mutations in 23 S r RNA gene.
基金Supported by Natural Science Foundation of Tianjin City(07JCYBJC16000)Project for Key Technology Integration and Enhancement of Students’Comprehensive Ability of Affiliated Animal Hospital of Tianjin Agricultural University(ZH004901)
文摘A biofilm refers to a group of organized bacteria attached to the surface of living or inanimate objects and surrounded by some macromolecules. It is rich in organic components such as polysaccharides,peptides and phospholipids,greatly increases the resistance of bacteria to antibacterial drugs,and can cause infections in humans and animals. At present,the measure to prevent the infections is to prevent microbial colonies from adhering to the surface of the objects,which will help to improve the therapeutic effect of clinically serious infectious diseases. In addition,the identification and inhibition of biofilm formation genes is also an important research direction to control such infections. In this paper,molecular mechanisms of bacterial biofilm resistance to drugs that has caused widespread concern were summarized.
基金This work was supported by an Erasmus+Mobility Studentship(ref DK KOBENHA 57)awarded to DJ.The funder was not involved in the interpretation of results or writing of the article.
文摘Bacterial resistance to antibiotics is an increasing threat to global healthcare systems.We therefore sought compounds with potential to reverse antibiotic resistance in a clinically relevant multi-drug resistant isolate of Escherichia coli(NCTC 13400).200 natural compounds with a history of either safe oral use in man,or as a component of a traditional herb or medicine,were screened.Four compounds;ellagic acid,propyl gallate,cinchonidine and cepharanthine,lowered the minimum inhibi-tory concentrations(MICs)of tetracycline,chloramphenicol and tobramycin by up to fourfold,and when combined up to eightfold.These compounds had no impact on the MICs of ampicillin,erythromycin or trimethoprim.Mechanistic studies revealed that while cepharanthine potently suppressed efflux of the marker Nile red from bacterial cells,the other hit com-pounds slowed cellular accumulation of this marker,and/or slowed bacterial growth in the absence of antibiotic.Although cepharanthine showed some toxicity in a cultured HEK-293 mammalian cell-line model,the other hit compounds exhibited no toxicity at concentrations where they are active against E.coli NCTC 13400.The results suggest that phytochemicals with capacity to reverse antibiotic resistance may be more common in traditional medicines than previously appreciated,and may offer useful scaffolds for the development of antibiotic-sensitising drugs.
基金Supported by the Application Technology Research and Development Project in Heilongjiang Province of China(PC13S03)the Foundation of Heilongjiang Province Educational Committee of China(11541030)。
文摘Salmonella gallinarum has shown multiple drug resistance(MDR),especially high level fluoroquinolone(FQ)resistance in recent years.To determine whether the active efflux system was responsible for high-level FQ resistance,this research studied AcrAB efflux pump in Salmonella gallinarum on molecular level.The resistant strains were induced by standard strain C79-13 with ciprofloxacin in vitro.With carbonylcyanide-p-chlorophenyl hydrazone(CCCP)as an energy inhibitor,efflux inhibition test initially showed the potential impact of efflux pump on drug resistance.Sequence analysis of acrA gene indicated that gene mutation of AcrAB efflux pump was not definitely associated with MDR and drug resistance level of Salmonella gallinarum.Detected by competitive RT-PCR,the mRNA expression of acrA and acrB genes in the resistant strains significantly increased(p<0.01)compared with that of the control strain C79-13.The mRNA expression level of acrB gene(increased from 1.6-to 2.9-folds)was consistent with that of acrA gene(increased from 1.6-to 2.8-folds),which increased with the drug resistance level.However,gene mutation of acrA gene showed no correlation with its mRNA expression level,indicating that gene mutation did not affect the expression of AcrAB pump itself.The results suggested that the overexpression rather than the gene mutation of AcrAB efflux pump was an important factor causing the high level drug resistance of Salmonella gallinarum.
文摘The present study focused on MexCD-OprJ efflux pump and its regulatory gene nfxB in multidrug resistant (MDR) clinical isolates of Pseudomonas aeruginosa collected from Kerala, South India. Semi-quantitative reverse transcription-PCR technique was employed to detect hyperexpression of the efflux pump gene, mexD. Amplicons from nfxB gene of isolates hyperexpressing the efflux pump were sequenced for mutational and phylogenetic analysis. Among 29 isolates of MDR P. aeruginosa, increased mexD transcription was detected in 10.3% of the isolates when compared with P. aeruginosa reference strain, PAO (MTCC-3541). Various synonymous and non-synonymous mutations in nfxB regulatory gene sequences were detected. Notably, mutations detected in the strains designate Pa6 and Pa7 have been found to be novel and are hitherto unreported in GenBank data base. The genetic divergence and homogeneity of the nfxB regulatory gene sequences of mexCD-oprJ operon were clearly apparent in the phylogram generated employing similar sequences retrieved from the public database.
文摘Purpose: Myocardial revascularization by coronary artery bypass grafting (CABG) in ischemic heart disease patients has direct impact on hemodynamic parameters in the immediate post-operative period. The peri-operative cardiovascular functioning is an important determinant for outcome of surgery. In On-Pump CABG (ONCAB), the cardiopulmonary bypass has a negative effect on myocardium. Off-Pump CABG (OPCAB) avoids the effect of CPB but complete revascularization with difficult positioning of heart is technically demanding. This study is aimed to compare the cardiovascular functioning in the immediate post-operative period after OPCAB and ONCAB. Methods: Total 106 patients were operated for CABG from January 2015 to June 2016, of which 75 patients were operated for OPCAB and 31 patients were operated for ONCAB. For the comparison, hemodynamic parameters were measured during anesthesia before surgery, postoperatively after 1 and 4 hours (h) in the ICU, and in the morning after surgery, approximately after 20 h. Results: The time-dependent rise of hemodynamic parameters like Cardiac Output (CO), Cardiac Index (CI), Stroke volume (SV) and Left Ventricular Stroke Work Index (LVSWI) in the immediate post-operative hours (1 h and 4 h) are more predominant in OPCAB group than ONCAB group although the difference is eliminated mostly at 20 h. The better peripheral vasodilation after OPCAB causes immediate fall of Systemic Vascular Resistance Index (SVRI) after OPCAB. Conclusion: Better cardiovascular functioning immediately after OPCAB than ONCAB may be important for better hemodynamic stability. The difference is however eliminated after 24 hours indicating little significance in long term outcome.