Acquisition of daptomycin resistance in patients results in decreased virulence in Drosophila
Author(s)
Type
Journal Article
Abstract
Staphylococcus aureus can acquire antimicrobial resistance, which in turn may affect its pathogenic potential. Using a panel of paired clinical isolates collected before and after daptomycin resistance acquisition, most frequently through a single mprF mutation, we show a relationship between increasing daptomycin minimum inhibitory concentration and reduced virulence in a Drosophila systemic infection model. Analyzing toxin production, in vitro bacterial growth characteristics, and cell surface properties, we failed to link daptomycin resistance-related attenuated virulence to either reduced virulence factor production, reduced fitness, or any of the cell surface characteristics investigated. Competition assays in Drosophila also did not support any altered ability in immune evasion. Instead, using a panel of mutant flies defective for various immune components, we show that this daptomycin resistance-related attenuated virulence is mostly explained by greater susceptibility to the activity of Drosophila prophenoloxidase, a tyrosinase involved in melanization, but not to antimicrobial peptides or Bomanin antimicrobial effectors. Further investigation could not link daptomycin resistance-related attenuation of virulence to differential susceptibility to reactive oxygen species or quinones prominently associated with phenoloxidase bacterial-killing activity. Taken together, it appears that daptomycin resistance attenuates Staphylococcus aureus virulence through enhanced sensitivity to phenoloxidase based on a complex mechanism. Our study provides new insights into the understanding of the crosstalk between antimicrobial resistance, escape from immune killing, and virulence.
Editor(s)
Kline, Kimberly A
Date Issued
2025-06-10
Date Acceptance
2025-04-09
Citation
Infection and Immunity, 2025, 93 (6)
ISSN
0019-9567
Publisher
American Society for Microbiology
Journal / Book Title
Infection and Immunity
Volume
93
Issue
6
Copyright Statement
© 2025 Lamy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
License URL
Identifier
10.1128/iai.00594-24
Subjects
Staphylococcus aureus
Drosophila melanogaster
host-pathogen interac tion
virulence
antimicrobial resistance
link between antimicrobial resistance and virulence
prophenoloxidase
antimicrobial peptides
daptomycin by 2a0c:5bc0:40:1008:1a60:24ff:fea6:cae5
Publication Status
Published
Article Number
e00594-24
Date Publish Online
2025-05-23