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Whole Genome Sequencing Identifies MprF Mutations in a Genetically Diverse Population of Daptomycin Non-susceptible Staphylococcus aureus in Australia
Journal article   Open access   Peer reviewed

Whole Genome Sequencing Identifies MprF Mutations in a Genetically Diverse Population of Daptomycin Non-susceptible Staphylococcus aureus in Australia

Candice Lim, Geoffrey W Coombs, Denise A Daley, Princy Shoby and Shakeel Mowlaboccus
International journal of antimicrobial agents, Vol.63(5), 107144
2024
DOI: https://doi.org/10.1016/j.ijantimicag.2024.107144
PMID: 38494147
Appears in  Open Access via Read & Publish Agreements
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CC BY V4.0,  Open Access

Abstract

antimicrobial resistance daptomycin MprF Staphylococcus aureus whole genome sequencing
Daptomycin is one of the few last-line antimicrobials available for the treatment of multidrug-resistant Staphylococcus aureus infections. An increasing number of daptomycin non-susceptible S. aureus infections has been reported worldwide, including Australia. Resistance to daptomycin is multifactorial and involves chromosomal mutations in genes encoding proteins involved in cell membrane and cell wall synthesis. In this study, we performed broth microdilution (BMD) to determine the daptomycin minimum inhibitory concentration (MIC) of 66 clinical isolates of S. aureus previously reported as daptomycin non-susceptible by the VITEK® 2. We used whole genome sequencing to characterise the isolates and screened the genomes for mutations associated with daptomycin non-susceptibility. Only 56 of the 66 isolates had a daptomycin MIC >1 mg/L by BMD. Although the 66 isolates were polyclonal, ST22 was the predominant sequence type and one-third of the isolates were multidrug resistant. Daptomycin non-susceptibility was primarily associated with MprF mutations – at least one MprF mutation was identified in the 66 isolates. Twelve previously reported MprF mutations associated with daptomycin non-susceptibility were identified in 83% of the isolates. Novel MprF mutations identified included P314A, P314F, P314T, S337T, L341V, F349del, and T423R. In conclusion, daptomycin non-susceptible S. aureus causing infections in Australia are polyclonal and harbour MprF mutation(s). The identification of multidrug-resistant daptomycin non-susceptible S. aureus is a public health concern.

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