Publikationsdatenbank

From heteroresistance to resistance:
a single nucleotide polymorphism (SNP) homogenizes population plasticity of gene amplification based heteroresistance (2023)

Art

Vortrag

Autoren

Kupke, Johannes (WE 7)

Brombach, Julian (WE 7)

Wolf, Silver Anthony

Thrukonda, Lakshmipriya

Ghazisaeedi, Fereshteh (WE 7)

Hanke, Dennis (WE 7)

Semmler, Torsten

Tedin, Karsten (WE 7)

Schreiber, Frank

Nordholt, Niclas

Lübke-Becker, Antina (WE 7)

Fulde, Marcus (WE 7)

Kongress

Zoonoses 2023 - International Symposium on Zoonoses Research

Berlin, 09. – 11.10.2023

Quelle

Zoonoses 2023 - International Symposium on Zoonoses Research : benefits and chances of one health research : program and abstracts — German Research Platform for Zoonoses (Hrsg.)

— S. 99

Sprache

Englisch

Verweise

URL (Volltext): https://evis.events/event/260/attachments/99/255/Zoonoses%202023%20-%20Book%20of%20Abstracts.pdf

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

Introduction
Heteroresistance (HR) describes the ability of a subpopulation to grow in the presence of inhibitory
antibiotic concentrations. We found HR to ceftazidime (CAZ) in a clinical Enterobacter cloacae complex
(ECC) strain (IMT49658).
Material & Methods
We performed extensive phenotypic (population analysis profiles, stability analysis of resistance, Scan-
Lag) and molecular microbiological techniques (qRT-PCR, whole genome sequencing, raw read analysis)
in order to show the plasticity and mechanism of HR in this ECC strain. We re-investigated the genome
and phenotype of IMT 49658 after long-term evolution in 32 g/ml CAZ.
Results
WGS detected a plasmidal gene amplification with β-lactamase ampC blaDHA-1. qRT-PCR showed a
high genomic copy number of blaDHA 1 in resistant subpopulations, decreasing when they reverted
to susceptibility. Gene amplifications varied in single cells of one colony (raw read analysis). Resistant
subpopulations showed heterogeneous lag times in ScanLag. After evolving ECC for 21 days in CAZ,
we discovered a SNP in dacB, encoding for a stop codon. This mutant displayed low amplification levels
but resistance in disk diffusion and homogenous lag times.
Conclusion
Long-term evolution in antibiotic niches drives the emergence of new resistant mutants, balancing the
fitness costs of e.g., gene amplifications. Comprehension of the transition from HR to resistance is
inevitable for successful treatment of infections from zoonotic bacteria.