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Updated: Apr 15, 2026

Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Impact of daptomycin resistance on Staphylococcus aureus virulence
David R Cameron1, Lawrence I Mortin, Aileen Rubio
1a Department of Microbiology ; School of Biomedical Sciences; Monash University ; Melbourne , Australia.
Abstract:
Daptomycin resistance (DAP(R)) in Staphylococcus aureus is associated with mutations in genes that are also implicated in staphylococcal pathogenesis. Using a laboratory-derived series of DAP exposed strains, we showed a relationship between increasing DAP MIC and reduced virulence in a Galleria mellonella infection model. Point mutations in walK and rpoC led to cumulative reductions in virulence and simultaneous increases in DAP MIC. A point mutation to mprF did not impact on S.aureus virulence; however deletion of mprF led to virulence attenuation and hyper-susceptibility to DAP. To validate our findings in G. mellonella, we confirmed the attenuated virulence of select isolates from the laboratory-derived series using a murine septicaemia model. As a corollary, we showed significant virulence reductions for clinically-derived DAP(R) isolates compared to their isogenic, DAP-susceptible progenitors (DAP(S)). Intriguingly, each clinical DAP(R) isolate was persistent in vivo. Taken together, it appears the genetic correlates underlying daptomycin resistance in S. aureus also alter pathogenicity.
Insights
Mutations causing daptomycin resistance (DAP(R)) in Staphylococcus aureus also reduce its virulence. This study investigated the link between DAP(R) genetic changes and pathogenicity in infection models.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Daptomycin resistance (DAP(R)) in Staphylococcus aureus is a growing clinical concern.
- Mutations conferring DAP(R) are often found in genes linked to bacterial pathogenesis.
Purpose of the Study:
- To investigate the relationship between genetic mutations causing DAP(R) and Staphylococcus aureus virulence.
- To determine if DAP(R) mutations impact pathogenicity in vivo.
Main Methods:
- Laboratory-evolved DAP-resistant Staphylococcus aureus strains were generated.
- Virulence was assessed using Galleria mellonella and murine infection models.
- Genetic mutations (walK, rpoC, mprF) and their effect on DAP minimum inhibitory concentration (MIC) and virulence were analyzed.
Main Results:
- Increasing DAP MIC correlated with reduced virulence in Galleria mellonella.
- Specific mutations in walK and rpoC cumulatively decreased virulence and increased DAP MIC.
- mprF deletion attenuated virulence and increased susceptibility to DAP.
- Clinical DAP(R) isolates showed reduced virulence compared to susceptible counterparts and were persistent in vivo.
Conclusions:
- Genetic determinants of daptomycin resistance in Staphylococcus aureus significantly impact bacterial pathogenicity.
- Daptomycin resistance mechanisms may involve trade-offs with virulence, but clinical isolates can remain persistent.
- Understanding these genetic alterations is crucial for managing Staphylococcus aureus infections.
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