Genomic and Phenotypic Characterization of Mupirocin Resistant Staphylococcus aureus Clinical Isolates

Virgillio, A. M.; Felton, E. A.; Jackson, J. K.; Kennedy, S. J.; Becker, D. N.; Lima, A.; Atrubin, K.; Cella, E.; Azarian, T.; Silbert, S.; Shaw, L. N.; Kim, K.

doi:10.1101/2025.04.16.648996

bioRxiv · 10.1101/2025.04.16.648996

Genomic and Phenotypic Characterization of Mupirocin Resistant Staphylococcus aureus Clinical Isolates

Virgillio, A. M.·Felton, E. A.·Jackson, J. K.·Kennedy, S. J.·Becker, D. N.·Lima, A.·Atrubin, K.·Cella, E.·Azarian, T.·Silbert, S.·Shaw, L. N.·Kim, K.

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Abstract

BackgroundColonization with Staphylococcus aureus is a risk factor for subsequent infection. Decolonization with the topical antibiotic mupirocin is effective and reduces the risk of subsequent S. aureus infection for both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains but may select for mupirocin-resistant isolates. MethodsWe characterized oxacillin and mupirocin susceptibility amongst 384 S. aureus strains isolated from clinical samples isolated 2017-2023 in Tampa, Florida, spanning strains collected before and after the onset of the COVID-19 pandemic. Whole genome sequencing of bacterial isolates was conducted in parallel and correlated with drug susceptibility profiles. ResultsMupirocin resistance (MupR) was nearly exclusively present in MRSA strains (103/106 97.1% of MupR; 103/299 34.4% of MRSA). Although our hospital protocol for decolonization shifted to povidone iodine in the Post-COVID period, the overall prevalence of MupR did not change in Pre-COVID and Post-COVID samples (28.9% vs 26%). Genotype correlated with antibiotic susceptibility with low level MupR (MupLR), linked to mutations in ileS and high level MupR (MupHR), linked to the presence of mupA. Genome analysis revealed that most MupR strains fell into three sequence types (ST) falling into two major clonal complexes (CC): CC8 ST8 (including Community-Associated MRSA strains USA300 and USA500), CC5 ST5 (associated with Healthcare-Associated MRSA such as USA100), and CC5 ST3390. ST3390 isolates had the highest prevalence of MupR (30/36 83%; MupHR 20/36 55.6%; MupLR 10/36 27.8%). ConclusionsMupirocin resistance was prevalent in our hospital MRSA strains. We also found evidence for emergence and persistence of ST3390 MRSA-MupR strains in Florida. Key pointsO_LIIn a survey of clinical isolates in Florida, 34.4% of MRSA strains were mupirocin resistant. C_LIO_LIMupirocin resistance correlated with mutations in ileS or carriage of mupA. C_LIO_LIWe found evidence for emergence of MRSA mupirocin-resistant strains that were sequence type ST3390. C_LI

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Virgillio, A. M., Felton, E. A., Jackson, J. K., Kennedy, S. J., Becker, D. N., Lima, A., Atrubin, K., Cella, E., Azarian, T., Silbert, S., Shaw, L. N., Kim, K.. 2025-04-21. Genomic and Phenotypic Characterization of Mupirocin Resistant Staphylococcus aureus Clinical Isolates. https://doi.org/10.1101/2025.04.16.648996

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