Langlois Benedicte, Guerin Francois, Isnard Christophe, Gakuba Clement, Du Cheyron Damien, Giard Jean-Christophe, Brisse Sylvain, Le Hello Simon, Gravey Francois
Univ de Caen Normandie, Univ Rouen Normandie, INSERM, DYNAMICURE, Caen, France.
Department of Infectious Agents, Bacteriology, CHU Caen, Caen, France.
mSphere. 2024 Dec 19;9(12):e0070424. doi: 10.1128/msphere.00704-24. Epub 2024 Nov 29.
Acquired antimicrobial resistance and metabolic changes are central for bacterial host adaptation during the long-term hospitalization of patients. We aimed to analyze the genomic and phenotypic evolution of enteric populations in long-term intensive care unit (ICU) patients. Weekly rectal swabs were prospectively collected from all patients admitted to the ICU in a teaching hospital from December 2018 to February 2019. The inclusion criterion for patients was hospitalization for more than 15 days in the ICU without any history of hospitalization or antibiotic treatment for the 3 months prior to admission. Among them, enteric species complex (KpSC) populations were detected. For each isolate, extensive antimicrobial resistance profiles were determined using the disk diffusion method, and the whole genome was sequenced using an Illumina platform. typing methods, such as Multilocus Sequence Typing (MLST), core-genome MLST, SNP typing, resistome characterization and mutation point detection, were applied. During the study period, 471 patients were admitted to ICUs. Among them, 21 patients met the inclusion criteria, and only 5 patients (24%) carried unique and distinct KpSC populations during 2-10 weeks in the gut that as detected at admission and excluding acquisition during the ICU stay. One patient showed a rare ST1563 persistent carriage for 7 consecutive weeks, which displayed important antimicrobial resistance phenotype changes in the 2 last weeks. In-depth characterization and RNA sequencing of these strains revealed a mutation within the transcriptional regulator resulting in overexpression of the regulator and decreased expression of , which controls antibiotic efflux. This mutation also impacts tolerance to biliary salts. This study revealed the importance of endogenous colonization of KpSC populations in the gut throughout the patient's long-term ICU stay and highlighted the role of in drug susceptibility.
The species complex (KpSC) is one of the major causes of nosocomial infections, especially in intensive care unit (ICUs). These bacteria are frequently highly resistant to antibiotics, leading to an increase in morbidity and mortality. The origins of multidrug-resistant KpSC strains isolated from ICU patients are still unclear, with at least two hypotheses of acquisition paths: (i) endogenous KpSC populations that are or became resistant to antibiotics and/or (ii) hospital acquisition of circulating KpSC clones. Genomic changes observed in this study might reveal mechanisms to better adapt to KpSC in the patient's gut in the face of heavy ICU medical care pressure.
获得性抗菌药物耐药性和代谢变化是患者长期住院期间细菌适应宿主的核心因素。我们旨在分析长期重症监护病房（ICU）患者肠道菌群的基因组和表型进化。2018年12月至2019年2月期间，前瞻性地收集了一家教学医院ICU收治的所有患者的每周直肠拭子。患者的纳入标准为在ICU住院超过15天，且入院前3个月内无任何住院史或抗生素治疗史。其中，检测到了肠道菌种复合体（KpSC）菌群。对于每一株分离菌，采用纸片扩散法确定广泛的抗菌药物耐药谱，并使用Illumina平台对全基因组进行测序。应用了多种分型方法，如多位点序列分型（MLST）、核心基因组MLST、单核苷酸多态性分型、耐药基因组特征分析和突变点检测。在研究期间，471例患者入住ICU。其中，21例患者符合纳入标准，只有5例患者（24%）在入院时检测到且排除在ICU住院期间获得的情况下，在肠道中2至10周内携带独特且不同的KpSC菌群。1例患者连续7周出现罕见的ST1563持续携带，在最后2周显示出重要的抗菌药物耐药表型变化。对这些菌株的深入特征分析和RNA测序揭示了转录调节因子内的一个突变，导致该调节因子过表达，而控制抗生素外排的调节因子表达降低。该突变还影响对胆盐的耐受性。本研究揭示了在患者长期入住ICU期间，KpSC菌群在肠道内源性定植的重要性，并突出了该调节因子在药敏性中的作用。
菌种复合体（KpSC）是医院感染的主要原因之一，尤其是在重症监护病房（ICU）。这些细菌通常对抗生素高度耐药，导致发病率和死亡率增加。从ICU患者分离出的多重耐药KpSC菌株的来源仍不清楚，至少有两种获得途径的假设：（i）对抗生素耐药或变得耐药的内源性KpSC菌群，和/或（ii）医院获得的循环KpSC克隆。本研究中观察到的基因组变化可能揭示了在面对重症监护病房的重症医疗压力时，KpSC在患者肠道中更好适应的机制。
