{"title":"持续性谢瓦纳菌菌血症中出现的碳青霉烯耐药性:pdsS G547W 突变在适应性亚群动态中的作用。","authors":"Yao-Ting Huang, Po-Yu Liu","doi":"10.1186/s12941-024-00759-3","DOIUrl":null,"url":null,"abstract":"<p><p>This study elucidates the in vivo genetic mechanisms contributing to the emerging resistance to carbapenem in Shewanella algae through a lens of adaptive microbial evolution. Leveraging PacBio amplification-free sequencing, we tracked the evolution of β-lactam resistance in clinical isolates from a persistent S. algae bacteremia case amidst antimicrobial therapy. Our investigation spotlighted a recurrent G547W mutation in the sensor histidine kinase (pdsS), which was associated with the overexpression of an OmpA-like protein (pdsO) within a proteobacteria-specific sortase system. Intriguingly, we observed a recurrent switch between wild-type and G547W alleles, revealing an adaptive expansion and contraction of underlying cell subpopulations in response to β-lactam exposure. Comparative transcriptome analyses further demonstrated the overexpression of genes pivotal for membrane integrity, biofilm formation, immune evasion, and β-lactamase activation in resistant samples. This underscores the pre-existence of resistant cells at minuscule frequencies even without antibiotic pressure, potentially explaining the within-host emergence of resistance during antibiotic treatments. Our findings provide pivotal insights into the dynamic genetic adaptations of S. algae under therapeutic pressures, unmasking intricate resistance mechanisms and highlighting the critical role of subpopulation dynamics in treatment outcomes.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"102"},"PeriodicalIF":4.6000,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580497/pdf/","citationCount":"0","resultStr":"{\"title\":\"Emergence of carbapenem resistance in persistent Shewanella algae bacteremia: the role of pdsS G547W mutation in adaptive subpopulation dynamics.\",\"authors\":\"Yao-Ting Huang, Po-Yu Liu\",\"doi\":\"10.1186/s12941-024-00759-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study elucidates the in vivo genetic mechanisms contributing to the emerging resistance to carbapenem in Shewanella algae through a lens of adaptive microbial evolution. Leveraging PacBio amplification-free sequencing, we tracked the evolution of β-lactam resistance in clinical isolates from a persistent S. algae bacteremia case amidst antimicrobial therapy. Our investigation spotlighted a recurrent G547W mutation in the sensor histidine kinase (pdsS), which was associated with the overexpression of an OmpA-like protein (pdsO) within a proteobacteria-specific sortase system. Intriguingly, we observed a recurrent switch between wild-type and G547W alleles, revealing an adaptive expansion and contraction of underlying cell subpopulations in response to β-lactam exposure. Comparative transcriptome analyses further demonstrated the overexpression of genes pivotal for membrane integrity, biofilm formation, immune evasion, and β-lactamase activation in resistant samples. This underscores the pre-existence of resistant cells at minuscule frequencies even without antibiotic pressure, potentially explaining the within-host emergence of resistance during antibiotic treatments. Our findings provide pivotal insights into the dynamic genetic adaptations of S. algae under therapeutic pressures, unmasking intricate resistance mechanisms and highlighting the critical role of subpopulation dynamics in treatment outcomes.</p>\",\"PeriodicalId\":8052,\"journal\":{\"name\":\"Annals of Clinical Microbiology and Antimicrobials\",\"volume\":\"23 1\",\"pages\":\"102\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-11-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580497/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Clinical Microbiology and Antimicrobials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12941-024-00759-3\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Clinical Microbiology and Antimicrobials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12941-024-00759-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Emergence of carbapenem resistance in persistent Shewanella algae bacteremia: the role of pdsS G547W mutation in adaptive subpopulation dynamics.
This study elucidates the in vivo genetic mechanisms contributing to the emerging resistance to carbapenem in Shewanella algae through a lens of adaptive microbial evolution. Leveraging PacBio amplification-free sequencing, we tracked the evolution of β-lactam resistance in clinical isolates from a persistent S. algae bacteremia case amidst antimicrobial therapy. Our investigation spotlighted a recurrent G547W mutation in the sensor histidine kinase (pdsS), which was associated with the overexpression of an OmpA-like protein (pdsO) within a proteobacteria-specific sortase system. Intriguingly, we observed a recurrent switch between wild-type and G547W alleles, revealing an adaptive expansion and contraction of underlying cell subpopulations in response to β-lactam exposure. Comparative transcriptome analyses further demonstrated the overexpression of genes pivotal for membrane integrity, biofilm formation, immune evasion, and β-lactamase activation in resistant samples. This underscores the pre-existence of resistant cells at minuscule frequencies even without antibiotic pressure, potentially explaining the within-host emergence of resistance during antibiotic treatments. Our findings provide pivotal insights into the dynamic genetic adaptations of S. algae under therapeutic pressures, unmasking intricate resistance mechanisms and highlighting the critical role of subpopulation dynamics in treatment outcomes.
期刊介绍:
Annals of Clinical Microbiology and Antimicrobials considers good quality, novel and international research of more than regional relevance. Research must include epidemiological and/or clinical information about isolates, and the journal covers the clinical microbiology of bacteria, viruses and fungi, as well as antimicrobial treatment of infectious diseases.
Annals of Clinical Microbiology and Antimicrobials is an open access, peer-reviewed journal focusing on information concerning clinical microbiology, infectious diseases and antimicrobials. The management of infectious disease is dependent on correct diagnosis and appropriate antimicrobial treatment, and with this in mind, the journal aims to improve the communication between laboratory and clinical science in the field of clinical microbiology and antimicrobial treatment. Furthermore, the journal has no restrictions on space or access; this ensures that the journal can reach the widest possible audience.