Publication Database

Heteroresistance in Enterobacter cloacae complex caused by variation in transient gene amplification events (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Kupke, Johannes (WE 7)

Brombach, Julian (WE 7)

Fang, Yuwen

Wolf, Silver A.

Thrukonda, Lakshmipriya

Ghazisaeedi, Fereshteh (WE 7)

Kuropka, Benno

Hanke, Dennis (WE 7)

Semmler, Torsten

Nordholt, Niclas

Schreiber, Frank

Tedin, Karsten (WE 7)

Lübke-Becker, Antina (WE 7)

Steiner, Ulrich K.

Fulde, Marcus (WE 7)

Quelle

npj antimicrobials and resistance

Bandzählung: 3

Heftzählung: 1

Seiten: Artikel 13

ISSN: 2731-8745

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s44259-025-00082-7

DOI: 10.1038/s44259-025-00082-7

Pubmed: 39987221

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

Heteroresistance (HR) in bacteria describes a subpopulational phenomenon of antibiotic resistant cells of a generally susceptible population. Here, we investigated the molecular mechanisms and phenotypic characteristics underlying HR to ceftazidime (CAZ) in a clinical Enterobacter cloacae complex strain (ECC). We identified a plasmid-borne gene duplication-amplification (GDA) event of a region harbouring an ampC gene encoding a β-lactamase blaDHA-1 as the key determinant of HR. Individual colonies exhibited variations in the copy number of the genes resulting in resistance level variation which correlated with growth onset (lag times) and growth rates in the presence of CAZ. GDA copy number heterogeneity occurred within single resistant colonies, demonstrating heterogeneity of GDA on the single-cell level. The interdependence between GDA, lag time and antibiotic treatment and the strong plasticity underlying HR underlines the high risk for misdetection of antimicrobial HR and subsequent treatment failure.