The acquisition of clinically relevant amoxicillin resistance in Streptococcus pneumoniae requires ordered horizontal gene transfer of four loci.

Details

Serval ID
serval:BIB_05977A135425
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The acquisition of clinically relevant amoxicillin resistance in Streptococcus pneumoniae requires ordered horizontal gene transfer of four loci.
Journal
PLoS pathogens
Author(s)
Gibson P.S., Bexkens E., Zuber S., Cowley L.A., Veening J.W.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
25/07/2022
Peer-reviewed
Oui
Volume
18
Number
7
Pages
e1010727
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Understanding how antimicrobial resistance spreads is critical for optimal application of new treatments. In the naturally competent human pathogen Streptococcus pneumoniae, resistance to β-lactam antibiotics is mediated by recombination events in genes encoding the target proteins, resulting in reduced drug binding affinity. However, for the front-line antibiotic amoxicillin, the exact mechanism of resistance still needs to be elucidated. Through successive rounds of transformation with genomic DNA from a clinically resistant isolate, we followed amoxicillin resistance development. Using whole genome sequencing, we showed that multiple recombination events occurred at different loci during one round of transformation. We found examples of non-contiguous recombination, and demonstrated that this could occur either through multiple D-loop formation from one donor DNA molecule, or by the integration of multiple DNA fragments. We also show that the final minimum inhibitory concentration (MIC) differs depending on recipient genome, explained by differences in the extent of recombination at key loci. Finally, through back transformations of mutant alleles and fluorescently labelled penicillin (bocillin-FL) binding assays, we confirm that pbp1a, pbp2b, pbp2x, and murM are the main resistance determinants for amoxicillin resistance, and that the order of allele uptake is important for successful resistance evolution. We conclude that recombination events are complex, and that this complexity contributes to the highly diverse genotypes of amoxicillin-resistant pneumococcal isolates.
Pubmed
Open Access
Yes
Create date
02/08/2022 13:44
Last modification date
15/08/2022 6:40
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