Journal article
Genome-wide mutagenesis identifies factors involved in MRSA vaginal colonization
Cell reports (Cambridge), Vol.44(3), 115421
03/13/2025
DOI: 10.1016/j.celrep.2025.115421
PMCID: PMC12483769
PMID: 40085646
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that colonizes various body sites, including the nares, skin, and vagina. During pregnancy, colonization can lead to dysbiosis, adverse pregnancy outcomes, and invasive disease. To identify genes contributing to MRSA vaginal fitness, we performed transposon sequencing (Tn-seq) using a murine model of vaginal colonization, identifying over 250 conditionally essential genes. Five genes were validated in our murine model, including those encoding the aerobic respiration protein QoxB, bacillithiol biosynthesis component BshB2, sialic acid catabolism enzyme NanE, and the staphylococcal regulator of respiration SrrAB. RNA-seq and comparative analysis identified over 30 SrrAB-regulated genes potentially important for fitness in vaginal-like conditions, particularly under oxygen stress. These findings highlight pathways such as aerobic respiration, bacillithiol biosynthesis, sialic acid catabolism, and transcriptional regulation that support MRSA’s competitive fitness in the vaginal tract.
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•Improved in vivo Tn-seq method identifies genes contributing to MRSA vaginal colonization•Genes for respiration, stress response and sialic acid catabolism affect competitive fitness•RNA-seq and comparative analyses link SrrAB-regulated genes to vaginal colonization
Lyon et al. identify genetic factors important for MRSA vaginal colonization through an in vivo Tn-seq screen. Validation reveals competitive fitness defects in qoxB, bshB2, nanE, and srrAB mutants. Cross-comparison of ΔsrrAB in vitro RNA-seq with vaginal transcriptomic data uncovers >30 SrrAB-regulated factors potentially driving MRSA vaginal fitness.
Details
- Title: Subtitle
- Genome-wide mutagenesis identifies factors involved in MRSA vaginal colonization
- Creators
- Laurie M. Lyon - University of Colorado Anschutz Medical CampusStephanie M. Marroquin - University of Colorado Anschutz Medical CampusJohn C. Thorstenson - University of Colorado Anschutz Medical CampusLuke R. Joyce - University of Colorado Anschutz Medical CampusErnesto J. Fuentes - University of IowaKelly S. Doran - University of Colorado Anschutz Medical CampusAlexander R. Horswill - University of Colorado Anschutz Medical Campus
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.44(3), 115421
- DOI
- 10.1016/j.celrep.2025.115421
- PMID
- 40085646
- PMCID
- PMC12483769
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Grant note
- NIH: 1F32AI186285-01 American Heart Association: 23POST1013835
We thank our funding sources: NIH 1R01AI170557 (E.J.F. and A.R.H.) , NIH R01Al153332 (K.S.D.) , NIH 5T32AI052066-19 (L.M.L.) , NIH 1F32AI186285-01 (S.M.M.) , and American Heart Association 23POST1013835 (L.R.J.) . We thank Dr. Anthony Richardson for providing the LAC transposon library and Dr. Christian Jenul for construction of strain AH5930. We also acknowl-edge Dr. Flavia Costa and Dr. Rebecca Keogh for their invaluable discussions and Dr. Tonya Brunetti for assisting in troubleshooting the Tn-seq data analysis.
- Language
- English
- Date published
- 03/13/2025
- Academic Unit
- Microbiology and Immunology; Biochemistry and Molecular Biology
- Record Identifier
- 9984800195902771
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