Microbial drug resistance最新文献

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Genomic Characterization of Escherichia coli Co-Producing KPC-2 and NDM-5 Carbapenemases Isolated from Intensive Care Unit in a Chinese Hospital. 从一家中国医院重症监护室分离出的共产 KPC-2 和 NDM-5 碳青霉烯酶的大肠埃希菌的基因组特征。
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2024-01-01 Epub Date: 2023-12-26 DOI: 10.1089/mdr.2023.0050
Qian Xu, Haoyi Lin, Wanting Liu, Yuxia Zhong, Yingchun Zhou, Zhenbo Xu, Dingqiang Chen
{"title":"Genomic Characterization of <i>Escherichia coli</i> Co-Producing KPC-2 and NDM-5 Carbapenemases Isolated from Intensive Care Unit in a Chinese Hospital.","authors":"Qian Xu, Haoyi Lin, Wanting Liu, Yuxia Zhong, Yingchun Zhou, Zhenbo Xu, Dingqiang Chen","doi":"10.1089/mdr.2023.0050","DOIUrl":"10.1089/mdr.2023.0050","url":null,"abstract":"<p><p><b><i>Background:</i></b> Around the world, carbapenemase-producing <i>Escherichia coli</i> is becoming more prevalent. The purpose of this research was to analyze the whole plasmid sequences from YL03 isolates of the <i>E. coli</i> strain that produce both KPC-2 and NDM-5 carbapenemases. <b><i>Materials and Methods:</i></b> Whole-genome sequencing (WGS) and analysis of <i>E. coli</i> strain YL03, which was isolated from a wound sample, was performed by Illumina Novaseq 6000 and Pacific Biosciences Sequel (PacBio, Menlo Park, CA) sequencers. Following that, the WGS results were used to predict and analyze the YL03 genome composition and function. A complete gene sequence for YL03 with the accession number CP093551 has been uploaded to GenBank. <b><i>Results:</i></b> The results showed that YL03 co-carried five resistance genes, which included <i>bla</i><sub>KPC-2</sub>, <i>bla</i><sub>NDM-5</sub>, <i>bla</i><sub>TEM-1B</sub>, <i>bla</i><sub>CTX-M-14</sub>, and <i>mdf(A)</i>. Furthermore, three resistance plasmids were found in YL03: pYL03-KPC, pYL03-NDM, and pYL03-CTX. Among them, the 53 kb-long pYL03-KPC plasmid belonging to the IncP, carried the replicase gene (<i>repA</i>) and the carbapenemase gene (<i>bla</i><sub>KPC-2</sub>). The <i>bla</i><sub>KPC-2</sub> gene was flanked by a composite transposon-like element (Tn3-[Tn3] tnpR-ISKpn27 <i>bla</i><sub>KPC-</sub>-ISKpn6). <b><i>Conclusions:</i></b> The YL03 strain co-carried <i>bla</i><sub>KPC-2</sub> and <i>bla</i><sub>NDM-5</sub> and had a unique multidrug resistance plasmid containing <i>bla</i><sub>KPC-2</sub>.</p>","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":" ","pages":"27-36"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acknowledgment of Reviewers 2023. 鸣谢 2023 年审稿人。
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2024-01-01 Epub Date: 2023-12-22 DOI: 10.1089/mdr.2023.29008.ack
{"title":"Acknowledgment of Reviewers 2023.","authors":"","doi":"10.1089/mdr.2023.29008.ack","DOIUrl":"10.1089/mdr.2023.29008.ack","url":null,"abstract":"","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":"30 1","pages":"61-62"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Concomitant Resistance to Cefiderocol and Ceftazidime/Avibactam in Two Carbapenemase-Producing Klebsiella pneumoniae Isolates from Two Lung Transplant Patients. 两名肺移植患者的两株产碳青霉烯酶的肺炎克雷伯菌分离株对头孢iderocol和头孢他啶/阿维巴坦同时耐药。
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2024-01-01 Epub Date: 2023-10-23 DOI: 10.1089/mdr.2023.0054
Greta Bellinzona, Cristina Merla, Marta Corbella, Elizabeth Nagy Iskandar, Elena Seminari, Angela Di Matteo, Stefano Gaiarsa, Greta Petazzoni, Davide Sassera, Fausto Baldanti, Aurora Piazza, Patrizia Cambieri
{"title":"Concomitant Resistance to Cefiderocol and Ceftazidime/Avibactam in Two Carbapenemase-Producing <i>Klebsiella pneumoniae</i> Isolates from Two Lung Transplant Patients.","authors":"Greta Bellinzona, Cristina Merla, Marta Corbella, Elizabeth Nagy Iskandar, Elena Seminari, Angela Di Matteo, Stefano Gaiarsa, Greta Petazzoni, Davide Sassera, Fausto Baldanti, Aurora Piazza, Patrizia Cambieri","doi":"10.1089/mdr.2023.0054","DOIUrl":"10.1089/mdr.2023.0054","url":null,"abstract":"<p><p>In this study, we present two cases of <i>Klebsiella pneumoniae</i>, one KPC-33- and one NDM-1-producing, showing resistance to cefiderocol and ceftazidime/avibactam, collected in the intensive care unit of a hospital in Northern Italy from two patients who had recently undergone lung transplantation. Whole-genome sequencing was performed to investigate the molecular features of these strains.</p>","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":" ","pages":"21-26"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acknowledgment of Reviewers 2023. 鸣谢 2023 年审稿人。
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2023-12-22 DOI: 10.1089/mdr.2023.29008.ack
{"title":"Acknowledgment of Reviewers 2023.","authors":"","doi":"10.1089/mdr.2023.29008.ack","DOIUrl":"https://doi.org/10.1089/mdr.2023.29008.ack","url":null,"abstract":"","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antimicrobial Resistance of Genital Mycoplasma and Ureaplasma: A Multicentre Study Over a 5-Year Period in Italy (2017–2021) 生殖器支原体和解脲支原体的抗菌药耐药性:意大利一项为期 5 年的多中心研究(2017-2021 年)
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2023-12-07 DOI: 10.1089/mdr.2023.0202
Matteo Pavoni, Luigi Principe, Claudio Foschi, Elisa Meroni, Elena Briozzo, Tiziana Lazzarotto, Simone Ambretti, Stefano Di Bella
{"title":"Antimicrobial Resistance of Genital Mycoplasma and Ureaplasma: A Multicentre Study Over a 5-Year Period in Italy (2017–2021)","authors":"Matteo Pavoni, Luigi Principe, Claudio Foschi, Elisa Meroni, Elena Briozzo, Tiziana Lazzarotto, Simone Ambretti, Stefano Di Bella","doi":"10.1089/mdr.2023.0202","DOIUrl":"https://doi.org/10.1089/mdr.2023.0202","url":null,"abstract":"","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":"31 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138590222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Description of a Case of Helicobacter pylori Infection with In Vitro Resistance to Tetracycline: An Exceptional Event with No Consequences? 描述一例对四环素具有体外抗药性的幽门螺杆菌感染病例:没有后果的例外事件?
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2023-12-07 DOI: 10.1089/mdr.2023.0247
Sylvain Merle, Stéphane Bland, L. Bénejat, A. Ducournau, Quentin Jehanne, Emilie Bessède, Marine Jauvain, Fréderic Heluwaert, P. Lehours
{"title":"Description of a Case of Helicobacter pylori Infection with In Vitro Resistance to Tetracycline: An Exceptional Event with No Consequences?","authors":"Sylvain Merle, Stéphane Bland, L. Bénejat, A. Ducournau, Quentin Jehanne, Emilie Bessède, Marine Jauvain, Fréderic Heluwaert, P. Lehours","doi":"10.1089/mdr.2023.0247","DOIUrl":"https://doi.org/10.1089/mdr.2023.0247","url":null,"abstract":"","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":"51 16","pages":""},"PeriodicalIF":2.6,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138591704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High Prevalence of Carbapenem-Resistant Enterobacterales Colonization Among Intensive Care Unit Patients in a Tertiary Hospital, China. 中国一家三级医院重症监护病房患者中碳青霉烯耐药性肠杆菌定殖的高患病率。
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2023-12-01 Epub Date: 2023-09-21 DOI: 10.1089/mdr.2023.0056
Shan-Jian Chen, Wei-Qing Zhang, Yu-Lan Lin, Yong-Bin Zeng, Shou-Tao Chen, Shu Wu, Zhen Xun, Bin Yang
{"title":"High Prevalence of Carbapenem-Resistant Enterobacterales Colonization Among Intensive Care Unit Patients in a Tertiary Hospital, China.","authors":"Shan-Jian Chen, Wei-Qing Zhang, Yu-Lan Lin, Yong-Bin Zeng, Shou-Tao Chen, Shu Wu, Zhen Xun, Bin Yang","doi":"10.1089/mdr.2023.0056","DOIUrl":"10.1089/mdr.2023.0056","url":null,"abstract":"<p><p>Intestinal colonization with carbapenem-resistant Enterobacterales (CRE) has been shown as a significant risk factor for subsequent CRE infections, especially in intensive care units (ICUs). The aim of this study was to determine the prevalence of intestinal CRE colonization among ICU patients in a Chinese tertiary hospital. Fecal sample screenings for CRE were performed on ICU patients weekly. Antibiotic-susceptibility profile of CRE strains was determined using the Vitek-2 analysis system and broth microdilution method. The carbapenemases of all isolates were determined by phenotypes and genotypes. Clonal relatedness was analyzed by pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing was used to identify the multilocus sequence type (ST), plasmid replicons, and insertion sequences (ISs) of isolates. The overall colonization rate of CRE was 40.4% (82/203). A total of 84 CRE strains were detected, mostly with <i>Klebsiella pneumoniae</i> (92.9%). Antibiotic susceptibility testing profile revealed that 84 CRE strains were resistant to most antibiotics except for tigecycline and colistin. The carbapenemase-encoding genes including <i>bla</i><sub>KPC-2</sub>, <i>bla</i><sub>NDM-1</sub>, and <i>bla</i><sub>IMP-4</sub> were detected, and <i>bla</i><sub>KPC-2</sub> was the predominant genotype (90.8%). A total of 9 STs were identified among 84 CRE strains, and ST11 was the most common type (83.3%). A variety of mobile genetic elements, including plasmids and ISs, were detected via online tool prediction. PFGE analysis of the 78 <i>K. pneumoniae</i> strains showed 8 different pulsotypes, and pulsotype A was highly prevalent. This study found that the prevalence of CRE colonization was alarmingly high in the ICU, and that effective infection control measures are urgently needed to prevent the dissemination of CRE.</p>","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":" ","pages":"568-575"},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prevalence of Extended-Spectrum Beta-Lactamase Resistance and CTX-M-Group 1 Gene in Escherichia coli from the Water and Sediment of Urbanized Mangrove Ecosystems of Kerala. 喀拉拉邦城市化红树林生态系统水和沉积物中大肠杆菌对β-内酰胺酶抗性和CTX-M 1组基因的扩展谱患病率。
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2023-12-01 Epub Date: 2023-10-26 DOI: 10.1089/mdr.2023.0089
Gopika Sivan, Divya P Sukumaran, Akhil Prakash Ezhuthanikkunnel, Mohamed Hatha Ammanamveetil Abdulla
{"title":"Prevalence of Extended-Spectrum Beta-Lactamase Resistance and CTX-M-Group 1 Gene in <i>Escherichia coli</i> from the Water and Sediment of Urbanized Mangrove Ecosystems of Kerala.","authors":"Gopika Sivan, Divya P Sukumaran, Akhil Prakash Ezhuthanikkunnel, Mohamed Hatha Ammanamveetil Abdulla","doi":"10.1089/mdr.2023.0089","DOIUrl":"10.1089/mdr.2023.0089","url":null,"abstract":"<p><p>The study aimed to determine the prevalence of extended-spectrum β-lactamase resistance and CTX-M-group 1 gene in <i>Escherichia coli</i> from the water and sediment of three urbanized mangrove ecosystems of Kerala. A total of 119 <i>E. coli</i> isolates were screened for antibiotic susceptibility to 16 antibiotics. According to the phylogenetic analysis of <i>E. coli</i> isolates, nonpathogenic group A and pathogenic group D (29.4% and 23.5%) were the predominant phylotypes found in water samples. The most frequent phylotypes found in sediment samples were nonpathogenic groups A and B1 (27.9% and 26.4%). The highest incidence of antibiotic resistance in <i>E. coli</i> was against cefotaxime and colistin (100%). A significant difference in the prevalence of CTX-M-group 1 gene was observed among <i>E. coli</i> isolates in water samples (<i>p</i> < 0.05). The results indicate a high prevalence of β-lactamase harboring <i>E. coli</i> in the mangrove ecosystems that can hamper mangrove-dependent aquaculture practices and human health.</p>","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":" ","pages":"582-588"},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50162105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Study on the Genome and Mechanism of Tigecycline Resistance of a Clinical Chryseobacterium indologenes Strain. 一株吲哚根金杆菌临床菌株的基因组及抗替加环素机制研究。
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2023-12-01 Epub Date: 2023-09-21 DOI: 10.1089/mdr.2023.0129
Yi Luo, Min Chen, Yujie Jiang, Weiqi Wang, Heping Wang, Li Deng, Zuguo Zhao
{"title":"Study on the Genome and Mechanism of Tigecycline Resistance of a Clinical <i>Chryseobacterium indologenes</i> Strain.","authors":"Yi Luo, Min Chen, Yujie Jiang, Weiqi Wang, Heping Wang, Li Deng, Zuguo Zhao","doi":"10.1089/mdr.2023.0129","DOIUrl":"10.1089/mdr.2023.0129","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> <i>Chryseobacterium indologenes</i> is a clinically relevant microorganism that has been on the rise, with multidrug-resistant (MDR) strains being reported. <i>C. indologenes</i> carrying <i>tet(X2)</i> has been demonstrated to be resistant to the antibiotic tigecycline, yet, sensitive to all other members of the tetracycline family. This inconsistency in resistance prompts an inquiry into the contribution of <i>tet(X2)</i> to tigecycline resistance in <i>C. indologenes</i>. <b><i>Materials and Methods:</i></b> In this study, we report on a comprehensive analysis of the genomic mechanisms underlying tigecycline resistance in a MDR <i>C. indologenes</i> strain (CI3125) that was resistant to tigecycline but sensitive to tetracycline, doxycycline, and minocycline. We used whole-genome sequencing, quantitative reverse transcription PCR, Western blot, antibiotic-degrading tests, and efflux pump inhibiting tests to reveal the mechanism of tigecycline resistance in <i>C. indologenes</i> and elucidate the inconsistency in the antibiotic resistance mechanism for the tetracycline family. <b><i>Results:</i></b> Our findings demonstrate that CI3125 carries 60 antibiotic resistance genes distributed on 6 different genetic islands (GIs), with the potential for horizontal transfer. Notably, the <i>tet(X2)</i> gene is located on GI06 of CI3125. Genetic environment analysis of <i>tet(X2)</i> showed that all <i>tet(X2)</i> genes in Flavobacterium and Bacteroides share a conservative and functional ribosome-binding site upstream. Contrary to expectation, our RT-qPCR showed that <i>tet(X2)</i> was not transcribed in CI3125, and Western blot suggested the absence of <i>tet(X2)</i> protein in CI3125. Rather, we demonstrate that minimum inhibitory concentration values for tigecycline decreased two- to eight<b>-</b>folds in the presence of five different efflux pump inhibitors [1-(1-naphthyl- methyl)-piperazine, phenyl-arginine-β-naphthylamide, verapamil, reserpine, and carbonyl cyanide 3-chlorophenylhydrazone]. This finding provides evidence for the involvement of efflux pumps in tigecycline resistance, which is likely to be a universal mechanism among <i>C. indologenes</i>. Our study proposes that the inconsistency in resistance to the tetracycline family in CI3125 may be ascribed to the silence of <i>tet(X2)</i> and the functions of efflux pumps for tigecycline. <b><i>Conclusions:</i></b> Overall, our results highlight the importance of genomic approaches in understanding the underlying mechanisms of antibiotic resistance in clinically relevant microorganisms. While <i>tet(X2)</i> in CI3125 is silent, our findings suggest that it may be horizontally spread through GIs. Hence, our findings have significant implications for the management of <i>C. indologenes</i> infections in clinical settings.</p>","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":" ","pages":"541-551"},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41104795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Impact of Substitutions at Positions 1 and 8 of Fluoroquinolones on the Activity Against Mutant DNA Gyrases of Salmonella Typhimurium. 氟喹诺酮类药物1和8位取代对鼠伤寒沙门氏菌突变DNA聚合酶活性的影响。
IF 2.6 4区 医学
Microbial drug resistance Pub Date : 2023-12-01 Epub Date: 2023-10-04 DOI: 10.1089/mdr.2023.0014
Pondpan Suwanthada, Siriporn Kongsoi, Nami Miura, Lawrence P Belotindos, Chayada Piantham, Jirachaya Toyting, Mwangala L Akapelwa, Ruttana Pachanon, Kentaro Koide, Hyun Kim, Jeewan Thapa, Chie Nakajima, Yasuhiko Suzuki
{"title":"The Impact of Substitutions at Positions 1 and 8 of Fluoroquinolones on the Activity Against Mutant DNA Gyrases of <i>Salmonella</i> Typhimurium.","authors":"Pondpan Suwanthada, Siriporn Kongsoi, Nami Miura, Lawrence P Belotindos, Chayada Piantham, Jirachaya Toyting, Mwangala L Akapelwa, Ruttana Pachanon, Kentaro Koide, Hyun Kim, Jeewan Thapa, Chie Nakajima, Yasuhiko Suzuki","doi":"10.1089/mdr.2023.0014","DOIUrl":"10.1089/mdr.2023.0014","url":null,"abstract":"<p><p>Although many drug-resistant nontyphoidal <i>Salmonella</i> (NTS) infections are reported globally, their treatment is challenging owing to the ineffectiveness of the currently available antimicrobial drugs against resistant bacteria. It is therefore essential to discover novel antimicrobial drugs for the management of these infections. In this study, we report high inhibitory activities of the novel fluoroquinolones (FQs; WQ-3810 and WQ-3334) with substitutions at positions R-1 by 6-amino-3,5-difluoropyridine-2-yl and R-8 by methyl group or bromine, respectively, against wild-type and mutant DNA gyrases of <i>Salmonella</i> Typhimurium. The inhibitory activities of these FQs were assessed against seven amino acid substitutions in DNA gyrases conferring FQ resistance to <i>S.</i> Typhimurium, including high-level resistant mutants, Ser83Ile and Ser83Phe-Asp87Asn by <i>in vitro</i> DNA supercoiling assay. Drug concentrations of WQ compounds with 6-amino-3,5-difluoropyridine-2-yl that suppressed DNA supercoiling by 50% (IC<sub>50</sub>) were found to be ∼150-fold lower than ciprofloxacin against DNA gyrase with double amino acid substitutions. Our findings highlight the importance of the chemical structure of an FQ drug on its antimicrobial activity. Particularly, the presence of 6-amino-3,5-difluoropyridine-2-yl at R-1 and either methyl group or bromine at R-8 of WQ-3810 and WQ-3334, respectively, was associated with improved antimicrobial activity. Therefore, WQ-3810 and WQ-3334 are promising candidates for use in the treatment of patients infected by FQ-resistant <i>Salmonella</i> spp.</p>","PeriodicalId":18701,"journal":{"name":"Microbial drug resistance","volume":" ","pages":"552-560"},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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