TY  - JOUR
A1  - Hamprecht, Axel
A1  - Sommer, Julian
A1  - Willmann, Matthias
A1  - Brender, Christina
A1  - Stelzer, Yvonne
A1  - Krause, Felix F.
A1  - Tsvetkov, Tsvetan
A1  - Wild, Florian
A1  - Riedel-Christ, Sara
A1  - Kutschenreuter, Julia
A1  - Imirzalioglu, Can
A1  - Gonzaga, Aitor
A1  - Nübel, Ulrich
A1  - Göttig, Stephan
T1  - Pathogenicity of clinical oxa-48 isolates and impact of the oxa-48 incl plasmid on virulence and bacterial fitness
T2  - Frontiers in microbiology
N2  - OXA-48 is the most common carbapenemase in Enterobacterales in Germany and one of the most frequent carbapenemases worldwide. Several reports have associated blaOXA–48 with a virulent host phenotype. To challenge this hypothesis, 35 OXA-48-producing clinical isolates of Escherichia coli (n = 15) and Klebsiella pneumoniae (n = 20) were studied in vitro, in vivo employing the Galleria mellonella infection model and by whole-genome sequencing. Clinical isolates belonged to 7 different sequence types (STs) in E. coli and 12 different STs in K. pneumoniae. In 26/35 isolates blaOXA–48 was located on a 63 kb IncL plasmid. Horizontal gene transfer (HGT) to E. coli J53 was high in isolates with the 63 kb IncL plasmid (transconjugation frequency: ∼103/donor) but low in isolates with non-IncL plasmids (<10–6/donor). Several clinical isolates were both highly cytotoxic against human cells and virulent in vivo. However, 63 kb IncL transconjugants generated from these highly virulent isolates were not more cytotoxic or virulent when compared to the recipient strain. Additionally, no genes associated with virulence were detected by in silico analysis of OXA-48 plasmids. The 63 kb plasmid was highly stable and did not impair growth or fitness in E. coli J53. In conclusion, OXA-48 clinical isolates in Germany are diverse but typically harbor the same 63 kb IncL plasmid which has been reported worldwide. We demonstrate that this 63 kb IncL plasmid has a low fitness burden, high plasmid stability and can be transferred by highly efficient HGT which is likely the cause of the rapid dissemination of OXA-48 rather than the expansion of a single clone or gain of virulence.
KW  - OXA-48
KW  - carbapenemases
KW  - IncL
KW  - β-lactamases
KW  - virulence
KW  - fitness
KW  - plasmid
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51818
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-518187
SN  - 1664-302X
N1  - Copyright © 2019 Hamprecht, Sommer, Willmann, Brender, Stelzer, Krause, Tsvetkov, Wild, Riedel-Christ, Kutschenreuter, Imirzalioglu, Gonzaga, Nübel and Göttig. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 10
IS  - Art. 2509
SP  - 1
EP  - 12
PB  - Frontiers Media
CY  - Lausanne
ER  -