Publikationsdatenbank

poxtA amplification and mutations in 23S rRNA confer enhanced linezolid resistance in Enterococcus faecalis (2024)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Shan, Xinxin

Li, Chenglong

Zhang, Likuan

Zou, Chenhui

Yu, Runhao

Schwarz, Stefan (WE 7)

Shang, Yanhong

Li, Dexi

Brenciani, Andrea

Du, Xiang-Dang

Quelle

The journal of antimicrobial chemotherapy : JAC

Bandzählung: 79

Heftzählung: 12

Seiten: 3199 – 3203

ISSN: 0305-7453

Sprache

Englisch

Verweise

URL (Volltext): https://academic.oup.com/jac/article/79/12/3199/7781435?login=true

DOI: 10.1093/jac/dkae342

Pubmed: 39331515

Kontakt

Institut für Mikrobiologie und Tierseuchen

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51843 / 66949
mikrobiologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Objectives: This study aimed to explore the evolutionary patterns and resistance mechanisms of an Enterococcus faecalis strain harbouring poxtA under linezolid exposure.

Methods: A poxtA-carrying E. faecalis electrotransformant DJH702 with a linezolid minimum inhibitory concentration of 4 mg/L was exposed to increasing concentrations of linezolid (8-64 mg/L). The derived strains growing at 8, 16, 32 and 64 mg/L, designed DJH702_8, DJH702_16, DJH702_32 and DJH702_64, were obtained. The amplification and overexpression of poxtA were measured using sequencing and RT-PCR, the fitness cost by competition assays and the stability of the repeat units by serial passage.

Results: In all derived strains, high-level linezolid resistance develops through poxtA amplification. The relative copy numbers and transcription levels of poxtA were significantly increased. However, in the presence of higher linezolid concentrations, DJH702_32 and DJH702_64 showed reduced poxtA copy numbers and transcription levels compared with DJH702_8 and DJH702_16, but additional mutations in the 23S rRNA (G2505A). IS1216E-mediated formation of translocatable units with subsequent tandem amplification of these translocatable units supported the gain of poxtA segments. However, these amplicons were not stable and were lost frequently in the absence of a linezolid selection pressure. The amplification of the poxtA region did not result in a fitness cost, but mutations in 23S rRNA did.

Conclusions: poxtA-carrying E. faecalis electrotransformants used two distinct mechanisms to resist linezolid selection pressure: at lower concentrations, strains prioritized increasing poxtA expression levels, while at higher concentrations, a combination of increased poxtA expression and mutations in 23S rRNA was observed.