Research in microbiology · 2025
Transcriptional evaluation of functional genes of resistance, biofilm and quorum sensing in CTX-M15 ESBL-producing Klebsiella pneumoniae after meropenem concentration based on serum level.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Carstensen Suzana, Suss Paula Hansen, Ortis Gabriel Burato, Estrela Rita, Costa Edlaine Rijo, Moreira Fernanda L, Martins Thalissa Colodiano, Telles Joao Paulo, Tuon Felipe Francisco
Аннотация
BACKGROUND: Klebsiella pneumoniae is a leading cause of multidrug-resistant hospital-acquired infections. Resistance to carbapenems, particularly meropenem, is increasingly reported and often linked to β-lactamase production, porin alterations, and efflux pump overexpression. However, the immediate transcriptional response of clinical isolates to meropenem remains poorly characterized.
AIM: To investigate the transcriptomic response of a CTX-M-15-producing K. pneumoniae clinical isolate to clinically relevant meropenem exposure and identify potential non-enzymatic resistance and survival mechanisms.
METHODS: A meropenem-susceptible K. pneumoniae isolate was recovered from a bacteremic patient and confirmed to carry CTX-M-15, SHV-182, and OXA-1 β-lactamase genes. Time-kill assays were performed using serum-level meropenem concentrations. RNA was extracted at multiple time points (0, 10, 30, and 60 min) post-exposure, followed by RNA-sequencing. Differential gene expression was analyzed using DESeq2. Resistance genes were identified via genome sequencing and annotated using CARD and VFDB databases.
RESULTS: Meropenem exhibited a concentration-dependent bactericidal effect, with full inhibition sustained only at serum-level concentrations. Transcriptomic analysis revealed significant upregulation of genes linked to biofilm formation (e.g., osmB, lipoproteins), efflux pumps (mepA, acrB), and cell wall remodeling (murJ, lpoB). No differential expression was observed for blaCTX-M-15, blaOXA-1, or blaSHV-182. The transcriptional regulator ompR was induced, suggesting membrane permeability adjustments.
CONCLUSION: K. pneumoniae rapidly activates adaptive stress responses under meropenem exposure, primarily through biofilm-related genes, efflux pumps, and membrane remodeling rather than increased β-lactamase expression. These findings underscore the complexity of antimicrobial tolerance mechanisms and may inform novel therapeutic strategies targeting transcriptional plasticity in multidrug-resistant pathogens.
AIM: To investigate the transcriptomic response of a CTX-M-15-producing K. pneumoniae clinical isolate to clinically relevant meropenem exposure and identify potential non-enzymatic resistance and survival mechanisms.
METHODS: A meropenem-susceptible K. pneumoniae isolate was recovered from a bacteremic patient and confirmed to carry CTX-M-15, SHV-182, and OXA-1 β-lactamase genes. Time-kill assays were performed using serum-level meropenem concentrations. RNA was extracted at multiple time points (0, 10, 30, and 60 min) post-exposure, followed by RNA-sequencing. Differential gene expression was analyzed using DESeq2. Resistance genes were identified via genome sequencing and annotated using CARD and VFDB databases.
RESULTS: Meropenem exhibited a concentration-dependent bactericidal effect, with full inhibition sustained only at serum-level concentrations. Transcriptomic analysis revealed significant upregulation of genes linked to biofilm formation (e.g., osmB, lipoproteins), efflux pumps (mepA, acrB), and cell wall remodeling (murJ, lpoB). No differential expression was observed for blaCTX-M-15, blaOXA-1, or blaSHV-182. The transcriptional regulator ompR was induced, suggesting membrane permeability adjustments.
CONCLUSION: K. pneumoniae rapidly activates adaptive stress responses under meropenem exposure, primarily through biofilm-related genes, efflux pumps, and membrane remodeling rather than increased β-lactamase expression. These findings underscore the complexity of antimicrobial tolerance mechanisms and may inform novel therapeutic strategies targeting transcriptional plasticity in multidrug-resistant pathogens.