Antimicrobial Agents and Chemotherapy最新文献

{"title":"Evidence that remdesivir treatment reduces viral titers in patients with COVID-19.","authors":"Simon Boyd, Shivani Singh, William H K Schilling, Nicholas J White","doi":"10.1128/aac.01266-24","DOIUrl":"10.1128/aac.01266-24","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0126624"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of novel sequence type 12531 and O8:H7 serotype carbapenem-resistant <i>Escherichia coli</i> with strong swimming and intestinal epithelial cell barrier migration abilities.","authors":"Zhexiao Ma, Weiliang Zeng, Haifeng Liu, Huanchang Chen, Lulu Ye, Sichen Liu, Changrui Qian, Tieli Zhou, Jianming Cao","doi":"10.1128/aac.00805-24","DOIUrl":"10.1128/aac.00805-24","url":null,"abstract":"<p><p>Carbapenem-resistant <i>Enterobacteriaceae</i> have become widely prevalent globally because of antibiotic misuse and the spread of drug-resistant plasmids, where carbapenem-resistant <i>Escherichia coli</i> (CREC) is one of the most common and prevalent pathogens. Furthermore, <i>E. coli</i> has been identified as a member of normal gut flora and does not cause disease under normal circumstances. However, certain strains of <i>E. coli</i>, due to the expression of virulence genes, can cause severe intestinal and extra-intestinal infections. Therefore, clinically, drug resistance and pathogenic <i>E. coli</i> strains are significantly challenging to treat. In this study, a novel CREC strain DC8855 was isolated from the ascites of a patient with intestinal perforation, identified as a novel sequence type 12531 (ST12531) and an unreported serotype O8:H7. It was revealed that the resistance of ST12531 CREC was predominantly conferred by an IncFII(K) plasmid carrying <i>bla</i>_NDM-4. Furthermore, phylogenetic analysis indicated that this is the first discovery of such plasmids in China and the first identification in <i>E. coli</i>. Moreover, regarding virulence, the swimming assays, qRT-PCR, and <i>in vitro</i> intestinal barrier model indicated that DC8855 had significantly higher motility, flagella gene expression, and intestinal epithelial cell barrier migration ability than the other sequence types CREC strains (ST167 and ST410). In conclusion, this study identified novel CREC which was multidrug resistant as well as enteropathogenic and therefore requires continuous monitoring.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0080524"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frameshift mutations in the <i>mmpR5</i> gene can have a bedaquiline-susceptible phenotype by retaining a protein structure and function similar to wild-type <i>Mycobacterium tuberculosis</i>.","authors":"J Snobre, C J Meehan, W Mulders, L Rigouts, R Buyl, B C de Jong, A Van Rie, O Tzfadia","doi":"10.1128/aac.00854-24","DOIUrl":"10.1128/aac.00854-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Bedaquiline (BDQ) is crucial for the treatment of rifampicin-resistant tuberculosis, yet resistance threatens its effectiveness, mainly linked to mutations in the &lt;i&gt;mmpR5&lt;/i&gt; (&lt;i&gt;Rv0678&lt;/i&gt;) gene. While frameshift mutations are thought to produce non-functional proteins, we hypothesize that they can result in conserved proteins through late-stop codons or alternative reading frames and remain BDQ susceptible. We extracted 512 isolates harboring frameshift mutations in &lt;i&gt;mmpR5&lt;/i&gt; from the World Health Organization (WHO) catalog and 68 isolates with minimum inhibitory concentration (MIC) in mycobacterial growth indicator tube (MGIT) through a literature review. Using BioPython and AlphaFold2 we computed open (ORF) and alternative reading frames (ARFs) sequences and protein structures and assessed similarity to the wild type using an alignment and template modeling (TM)-score. Among the WHO 512 isolates, 24.8% were BDQ-sensitive. Out of 184 unique frameshift mutations with available nucleotide information, a late-stop codon in the ORF occurred for 32% of the mutations. Also, 40.7% resulted in a conserved sequence, through the ORF or one of the forward ARFs. In 68 isolates with available MGIT MIC data, the presence of late-stop codons in the ORF (OR 4.71, 95% CI 1.36-19.3) or a conserved reading frame (OR 10.4, 95% CI 2.07-102.9) were associated with BDQ sensitivity. Protein structures from the conserved sequences showed high similarity (TM &gt; 0.8). We show that frameshift mutations may retain BDQ susceptibility through late-stop codons in the ORF or conserved ARFs. These findings could improve the prediction of the BDQ phenotype from genomic data and have important implications for treatment decisions. Research Foundation-Flanders, Academy of Medical Sciences, the Wellcome Trust, the Government Department of Business, Energy and Industrial Strategy, the British Heart Foundation and Diabetes UK, and the Global Challenges Research Fund.IMPORTANCETuberculosis (TB), caused by &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;, remains the deadliest infectious disease and is particularly challenging to treat when it becomes drug-resistant. Bedaquiline (BDQ) is a recently recommended core drug for treating drug-resistant TB. However, resistance to bedaquiline is already emerging, primarily due to mutations in the &lt;i&gt;mmpR5&lt;/i&gt; gene. Identifying which mutations cause resistance and which do not is a critical knowledge gap. In particular, little is known about the effect of frameshift mutations, typically thought to make TB bacteria resistant to bedaquiline by producing non-functional proteins. Yet, one-quarter of isolates with a frameshift mutation are still susceptible to bedaquiline. How the bacteria produce a functional protein despite the frameshift mutation is unknown. We analyzed over 500 frameshift mutations using computational methods to model their effects on protein structure and bedaquiline resistance. Our findings revealed that some frameshift mutations ","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0085424"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local emergence and global evolution of <i>Neisseria gonorrhoeae</i> with high-level resistance to azithromycin.","authors":"Johan H Melendez, Vonetta L Edwards, Adamaris Muniz Tirado, Justin Hardick, Aditya Mehta, Jain Aluvathingal, Adonis D'Mello, Charlotte A Gaydos, Yukari C Manabe, Hervé Tettelin","doi":"10.1128/aac.00927-24","DOIUrl":"10.1128/aac.00927-24","url":null,"abstract":"<p><p>Antimicrobial resistance in <i>Neisseria gonorrhoeae</i> (Ng) has severely reduced treatment options, including azithromycin (AZM), which had previously been recommended as dual therapy with ceftriaxone. This study characterizes the emergence of high-level resistance to AZM (HLR-AZM) Ng in Baltimore, Maryland, USA, and describes the global evolution of HLR-AZM Ng. Whole genome sequencing (WGS) of 30 Ng isolates with and without HLR-AZM from Baltimore was used to identify clonality and resistance determinants. Publicly available WGS data from global HLR-AZM Ng (<i>n</i> = 286) and the Baltimore HLR-AZM Ng (<i>n</i> = 3) were used to assess the distribution, clonality, and diversity of HLR-AZM Ng. The HLR-AZM Ng isolates from Baltimore identified as multi-locus sequencing typing sequence type (ST) 9363 and likely emerged from circulating strains. ST9363 was the most widely disseminated ST globally represented in eight countries and was associated with sustained transmission events. The number of global HLR-AZM Ng, countries reporting these isolates, and strain diversity increased in the last decade. The majority (89.9%) of global HLR-AZM Ng harbored the A2059G mutation in all four alleles of the 23S rRNA gene, but isolates with two or three A2059G alleles, and alternative HLR-AZM mechanisms were also identified. In conclusion, HLR-AZM in Ng has increased in the last few years, with ST9363 emerging as an important gonococcal lineage globally. The 23S rRNA A2059G mutation is the most common resistance mechanism, but alternative mechanisms are emerging. Continued surveillance of HLR-AZM Ng, especially ST9363, and extensively drug-resistant Ng is warranted.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0092724"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vivo</i> pharmacodynamic evaluation of the novel nystatin derivative BSG005 in the invasive candidiasis and invasive pulmonary aspergillosis mouse models.","authors":"Alexander J Lepak, Justin Massey, Robert Zarnowski, Tine K Olesen, Ryley Jones, David R Andes","doi":"10.1128/aac.01234-24","DOIUrl":"10.1128/aac.01234-24","url":null,"abstract":"<p><p>Nystatin, a polyene, is one of the oldest antifungal drugs with wide <i>in vitro</i> potency. BSG005 is a novel, chemically modified, nystatin-like molecule in development for systemic therapy. We evaluated the pharmacokinetic/pharmacodynamic (PK/PD) relationships and target exposures using <i>in vivo</i> invasive pulmonary aspergillosis (IPA) and invasive candidiasis (IC) infection models for BSG005 against common fungal pathogens including <i>Aspergillus fumigatus</i>, <i>Candida albicans</i>, <i>Candida auris</i>, and <i>Candida glabrata</i>. For each species group, three to four strains were selected. Minimum inhibitory concentration (MIC) testing was done by Clinical Laboratory Standards Institute (CLSI) methods. Single-dose kinetics for BSG005 were performed at four dose levels. The immunosuppressed mouse IPA model was used for <i>A. fumigatus</i> studies. For all <i>Candida</i> studies, we utilized the neutropenic disseminated candidiasis model. We used quantitative PCR to enumerate <i>Aspergillus</i> in the lung and colony forming units (CFU) counts for <i>Candida</i> in the kidney. Treatment results were evaluated based on both area under the concentration-time curve (AUC)/MIC and maximum plasma concentration (<i>C</i>_max)/MIC exposures. The BSG005 MIC was 1 mg/L against all strains. Escalating doses of BSG005 resulted in increased effect and, in general, the dose-response curves within each species were concordant. The median 96-h AUC/MIC associated with net stasis was lowest at 6.08 for <i>C. glabrata</i>. Increasing exposures were needed for same outcome for <i>C. auris</i> at 18.7, <i>C. albicans</i> at 29.3, and <i>A. fumigatus</i> at 102.4. <i>C</i>_max/MIC targets for the four groups were 0.22, 0.48, 0.60, and 1.41. BSG005 demonstrated potent activity against a variety of fungal pathogens in the neutropenic mouse models. <i>C</i>_max/MIC PK/PD targets were numerically lower than other polyene studies using the same infection models.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0123424"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic epidemiology and genetic characteristics of clinical <i>Campylobacter</i> species cocirculating in West Bengal, India, 2019, using whole genome analysis.","authors":"Daichi Morita, Asish Kumar Mukhopadhyay, Goutam Chowdhury, Fumito Maruyama, Miyuki Kanda, Yuki Yamamoto, Hidetoshi Tahara, Piyali Mukherjee, Mainak Bardhan, Takanori Kumagai, Kei Kitahara, Shin-Ichi Miyoshi, Shanta Dutta, Teruo Kuroda","doi":"10.1128/aac.01108-24","DOIUrl":"https://doi.org/10.1128/aac.01108-24","url":null,"abstract":"<p><p><i>Campylobacter</i> species are the most common pathogens responsible for foodborne gastroenteritis worldwide. India is a region with frequent diarrheal infections and a high level of <i>Campylobacter</i> infection incidence, but the detailed genomic information is limited. This study aimed to characterize 112 isolates of <i>Campylobacter</i> from diarrhea patients at two hospitals in Kolkata, West Bengal, by whole genome analysis. The <i>Campylobacter</i> isolates consisted of 90 <i>C</i>. <i>jejuni</i>, 20 <i>C</i>. <i>coli</i>, and 2 <i>C</i>. <i>lari</i> isolates. Multilocus sequence typing analysis revealed that the largest sequence type (ST) populations were ST-2131 in <i>C. jejuni</i> and ST-830 in <i>C. coli</i> and seven novel STs were found in <i>C. jejuni</i> and one in <i>C. coli</i>. Notably, ST-2131, which is rarely seen elsewhere, was positive for a sialylated LOS-related gene (<i>wlaN +neuA + cstIII</i>) associated with Guillain-Barré syndrome. Antibiotic resistance factors predicted from the genome sequence included <i>blaOXA</i> variants (58.9%), <i>tet(O)</i> (54.5%), <i>tet(W)</i> (0.9%), <i>ant(6)-Ia</i> (0.9%), mutation in GyrA (T86I, T86I+D90N, T86I+P104S, T86I+D90<i>N</i>+P104S) (79.5%), and mutation in 23S rRNA (A2075G) (12.5%). In addition to the high drug resistance of <i>Campylobacter</i> in Kolkata, <i>Campylobacter</i> pathogens were circulating that may be associated with Guillain-Barré syndrome. This study indicates the importance of genomic analysis in the surveillance of pathogens, which provides genomic information on genetic diversity, virulence mechanisms, and determinants of antimicrobial resistance.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0110824"},"PeriodicalIF":4.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-AMP-I1, a novel venom-derived antimicrobial peptide from the wolf spider <i>Lycosa coelestis</i>.","authors":"Junyao Wang, Xi Liu, Yuxin Song, Zhonghua Liu, Xing Tang, Huaxin Tan","doi":"10.1128/aac.00424-24","DOIUrl":"https://doi.org/10.1128/aac.00424-24","url":null,"abstract":"<p><p>Antibiotic resistance has become a critical concern in recent years, and antimicrobial peptides may function as innovative antibacterial agents to address this issue. In this work, we identified a novel antimicrobial peptide, LC-AMP-I1, derived from the venom of <i>Lycosa coelestis</i>, demonstrating substantial antibacterial properties and minimal hemolytic activity. LC-AMP-I1 was subjected to additional assessment for antibacterial efficacy, anti-biofilm properties, drug resistance, stability, and cytotoxicity <i>in vitro</i>. It exhibited comparable antibacterial efficacy to melittin against six common clinical multidrug-resistant bacteria, effectively inhibiting biofilm formation and disrupting established biofilms. Additionally, LC-AMP-I1 demonstrated minimal bacterial resistance, excellent stability, negligible mammalian cell toxicity, low hemolytic activity, and appropriate selectivity for both normal and tumor cells. When combined with traditional antibiotics, LC-AMP-I1 exhibited additive or synergistic therapeutic effects. In a neutropenic mouse thigh infection model, LC-AMP-I1 exhibited a therapeutic effect in inhibiting bacterial proliferation <i>in vivo</i>. The mechanistic investigation indicated that LC-AMP-I1 could influence bacterial cell membrane permeability at low concentrations and directly disrupt structure-function at high concentrations. The results of this work indicate that LC-AMP-I1 may function as a viable alternative to traditional antibiotics in addressing multidrug-resistant bacteria.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0042424"},"PeriodicalIF":4.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-time evaluation of macozinone activity against <i>Mycobacterium tuberculosis</i> through bacterial nanomotion analysis.","authors":"Anthony Vocat, Amanda Luraschi-Eggemann, Claudia Antoni, Gino Cathomen, Danuta Cichocka, Gilbert Greub, Olga Riabova, Vadim Makarov, Onya Opota, Alfonso Mendoza, Stewart T Cole, Alexander Sturm","doi":"10.1128/aac.01318-24","DOIUrl":"https://doi.org/10.1128/aac.01318-24","url":null,"abstract":"<p><p>Novel drugs and improved diagnostics for <i>Mycobacterium tuberculosis</i> (MTB) are urgently needed and go hand in hand. We evaluated the <i>in vitro</i> activity of two benzothiazinone drug candidates (MCZ, PBTZ169; BTZ043) and their main metabolites against MTB using advanced nanomotion technology. The results demonstrated significant reductions in MTB viability within 7 h, indicating the potential for rapid, precise antibiotic susceptibility testing based on a phenotypic read-out in real time. PBTZ169 and H₂-PBTZ169 achieved 100% separation between the susceptible H37Rv and a resistant <i>dprE1</i> mutant strain NTB1. These findings support nanomotion technology's potential for faster antibiotic susceptibility testing of novel MTB drug candidates targeting the DprE1 enzyme that could reduce empirical treatment duration and antibiotic resistance selection pressure due to inaccurate treatments.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0131824"},"PeriodicalIF":4.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and <i>in vitro</i> pharmacological assessment of novel <i>N</i>-hydroxypyridinediones as hepatitis B virus ribonuclease H inhibitors.","authors":"Molly E Woodson, Holly F Walden, M Abdul Mottaleb, Maria Makri, Georgia-Myrto Prifti, Dimitrios Moianos, Vasiliki Pardali, Grigoris Zoidis, John E Tavis","doi":"10.1128/aac.01455-24","DOIUrl":"https://doi.org/10.1128/aac.01455-24","url":null,"abstract":"<p><p>We previously reported <i>N</i>-hydroxypyridinedione (HPD) compounds with mid-nanomolar efficacy and selectivity indexes around 300 against hepatitis B virus (HBV) replication. However, they lack pharmacological evaluation. Here, we report <i>in vitro</i> anti-HBV efficacy, cytotoxicity, and pharmacological characterization of 29 novel HPDs within seven subgroups. The best two compounds had EC₅₀s of 61 and 190 nM and selectivity indexes of 526 and 1,071. Compounds with one halogen on the major R group were most effective and compounds with large ether R groups were most cytotoxic. Compounds were not cytotoxic in primary human hepatocytes. All compounds were freely soluble in pHs reflecting plasma (7.4) and the gastrointestinal tract (5 and 6.5). Almost all highly soluble compounds were passively permeable at pH 5.0 and 7.4. Only 2 of 11 compounds tested were likely to be effluxed by p-glycoprotein. The most potent HPDs inhibited HBV replication over human ribonuclease H1 activity by 10-fold. Four of 19 compounds inhibited CYP2D6 >50%, but their CYP2D6 IC₅₀s were >8× higher than their anti-HBV EC₅₀. No compound substantially inhibited CYP3A4. Thirteen of 15 compounds had human microsomal half-lives >30 min with medium to low rates of intrinsic clearance. Eleven of 12 compounds bound plasma proteins by ≥80%; however, effects against HBV replication for only one would likely be physiologically relevant. These results identify two lead candidate HPDs with pharmacological characteristics resembling commercially available drugs that are suitable for <i>in vivo</i> pharmacological and efficacy studies.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0145524"},"PeriodicalIF":4.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into antibiotic resistance promoted by quinolone exposure.","authors":"Natassja G Bush, Isabel Diez-Santos, Pilla Sankara Krishna, Bernardo Clavijo, Anthony Maxwell","doi":"10.1128/aac.00997-24","DOIUrl":"https://doi.org/10.1128/aac.00997-24","url":null,"abstract":"<p><p>Quinolone-induced antibiotic resistance (QIAR) refers to the phenomenon by which bacteria exposed to sublethal levels of quinolones acquire resistance to non-quinolone antibiotics. We have explored this in <i>Escherichia coli</i> MG1655 using a variety of compounds and bacteria carrying a quinolone-resistance mutation in gyrase, mutations affecting the SOS response, and mutations in error-prone polymerases. The nature of the antibiotic-resistance mutations was determined by whole-genome sequencing. Exposure to low levels of most quinolones tested led to mutations conferring resistance to chloramphenicol, ampicillin, kanamycin, and tetracycline. The mutations included point mutations and deletions and could mostly be correlated with the resistance phenotype. QIAR depended upon DNA gyrase and involved the SOS response but was not dependent on error-prone polymerases. Only moxifloxacin, among the quinolones tested, did not display a significant QIAR effect. We speculate that the lack of QIAR with moxifloxacin may be attributable to it acting via a different mechanism. In addition to the concerns about antimicrobial resistance to quinolones and other compounds, QIAR presents an additional challenge in relation to the usage of quinolone antibacterials.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0099724"},"PeriodicalIF":4.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}