The Resistance Mechanism Governs Physiological Adaptation of Escherichia coli to Growth With Sublethal Concentrations of Carbapenem

Frontiers in Microbiology

Microbiology

Robert Geffers¹  Dirk Schlüter²  Pia Görner²  Sabrina Woltemate²  Stefan Ziesing²  Marius Vital²  Franca Schäfer²  Christina Brandenberger³ 

[1] Genomics Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany;Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hanover, Germany;Institute of Functional and Applied Anatomy, Hannover Medical School, Hanover, Germany;

关键词: antibiotic resistance;    Escherichia coli;    ecology;    physiology;    RNA-Seq;   

DOI  :  10.3389/fmicb.2021.812544

 received in 2021-11-10, accepted in 2021-12-20,  发布年份 2022

来源: Frontiers

【 摘 要 】

Factors governing resistance in carbapenem-resistant Enterobacteriaceae are manifold. Despite ample research efforts, underlying molecular mechanisms are still only partly understood. Furthermore, little is known on (eco)physiological consequences from resistance acquisition originating from distinct mechanisms in respective bacteria.In this study, we examined physiological adaptation of Escherichia coli clinical isolates exhibiting two distinct resistance mechanisms–either carrying a carbapenemase (n = 4, CARB) or alterations in porin-encoding genes (n = 6, POR)–during growth with sublethal concentrations of ertapenem in chemostat culture. Basic growth parameters based on optical density and flow-cytometric analyses as well as global gene expression patterns using RNA-Seq were recorded. We demonstrate that strategies to deal with the antibiotic were distinct between strains of the two groups, where (increased) expression of carbapenemases was the major response in CARB, whereas wide-spread alterations in gene-expression that promoted a survival-like phenotype was observed in POR. The response in POR was accompanied with “costs of resistance” resulting in reduced growth efficiencies compared with CARB that are intrinsic to that group and were also observed during growth without antibiotic challenge, however, at lower levels. All strains showed similar minimal inhibitory concentrations and did not form phylogenetic groups, indicating that results cannot be attributed to distinct resistance levels or phylogenetic relationships, but are indeed based on the resistance mechanism.

【 授权许可】

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Copyright © 2022 Schäfer, Görner, Woltemate, Brandenberger, Geffers, Ziesing, Schlüter and Vital.