{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:23:37Z","timestamp":1790803417056,"version":"4.1.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n Staphylococcus<\/jats:italic>\n species, particularly\n Staphylococcus aureus<\/jats:italic>\n , are leading opportunistic pathogens responsible for a wide range of infections, with antimicrobial resistance\u2014including high rates of macrolide resistance\u2014severely limiting treatment options. The\n msrA<\/jats:italic>\n gene encodes the ABC-F protein MsrA, which mediates inducible resistance to 14-membered macrolides and type B streptogramins. Despite its clinical and epidemiological relevance, the evolutionary forces, selective pressures, and transmission routes shaping\n msrA<\/jats:italic>\n in staphylococci remain insufficiently understood.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Six hundred and one complete staphylococcal\n msrA<\/jats:italic>\n coding sequences (CDSs) were retrieved from GenBank. Evolutionary analyses of\n msrA<\/jats:italic>\n included nucleotide diversity (\n \u03c0<\/jats:italic>\n ), selection metrics (\n \n d\n N<\/jats:sub>\n -d\n S<\/jats:sub>\n <\/jats:italic>\n , \u03c0\n a<\/jats:sub>\n \/\u03c0\n s<\/jats:sub>\n , Tajima\u2019s D, Fu\u2019s Fs, FUBAR, MEME, and aBSREL), and conservation mapping using DnaSP in relation to MsrA functional domains (UniProt P23212). Linkage disequilibrium (LD) was assessed using ZnS, Za, ZZ, and Wall\u2019s statistics. Recombination and transmission pathways were inferred using GARD, RDP4-embedded algorithms, SplitsTree network analysis, and the PHI test.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Forty-one\n msrA<\/jats:italic>\n allelic variants were determined, with five predominant alleles accounting for approximately 90% of CDSs; allele 19 was almost exclusive to\n S. aureus<\/jats:italic>\n . Nucleotide diversity was moderate (\n \u03c0<\/jats:italic>\n \u202f\u2248\u202f0.039\u20130.042), and strong purifying selection predominated (\u03c0\n a<\/jats:sub>\n \/\u03c0\n s<\/jats:sub>\n \u202f\u2248\u202f0.169;\n \n d\n N<\/jats:sub>\n -d\n S<\/jats:sub>\n <\/jats:italic>\n \u202f=\u202f\u22120.138\u202f\u00b1\u202f0.016; strongly negative Fu\u2019s Fs), with only four codons showing evidence of episodic positive selection. Three highly conserved regions were identified, mainly overlapping the inter-domain linker and the second nucleotide-binding domain across MsrA. Moderate-to-high LD with minimal decay indicated the persistence of only a limited number of successful allelic variants. Predominant\n msrA<\/jats:italic>\n alleles were largely plasmid-associated. Recombination analyses revealed frequent interspecies transfer within\n Staphylococcus<\/jats:italic>\n , with\n S. aureus<\/jats:italic>\n acting as a central donor to\n Staphylococcus chromogenes<\/jats:italic>\n and\n Staphylococcus saprophyticus<\/jats:italic>\n , as well as rare intergeneric transfers involving\n Citrobacter<\/jats:italic>\n ,\n Enterococcus<\/jats:italic>\n ,\n Corynebacterium<\/jats:italic>\n , and\n Pseudomonas<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These findings support a dual evolutionary strategy for\n msrA<\/jats:italic>\n : strong purifying selection preserves its essential ribosomal-protection function, while plasmid-mediated dissemination promotes the spread of fit alleles.\n S. aureus<\/jats:italic>\n appears to be a key reservoir and vector, facilitating both interspecies and intergeneric transmission. Clinically, this underscores the need for surveillance of plasmid-borne\n msrA<\/jats:italic>\n and targeted control of\n S. aureus<\/jats:italic>\n reservoirs to limit resistance to macrolides and type B streptogramins.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1815688","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:47:04Z","timestamp":1776836824000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Evolution and transmission landscape of the staphylococcal msrA gene mediating resistance to 14-membered macrolides and type B streptogramins"],"prefix":"10.3389","volume":"17","author":[{"given":"Davit","family":"Janelidze","sequence":"first","affiliation":[{"name":"One Health Institute, School of Science and Technology, University of Georgia","place":["Tbilisi, Georgia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Kobakhidze","sequence":"additional","affiliation":[{"name":"One Health Institute, School of Science and Technology, University of Georgia","place":["Tbilisi, Georgia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinatin","family":"Elbakidze","sequence":"additional","affiliation":[{"name":"One Health Institute, School of Science and Technology, University of Georgia","place":["Tbilisi, Georgia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamuka","family":"Kotetishvili","sequence":"additional","affiliation":[{"name":"One Health Institute, School of Science and Technology, University of Georgia","place":["Tbilisi, Georgia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref1","volume-title":"Categorical Data Analysis","author":"Agresti","year":"2013"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"733","DOI":"10.3390\/antibiotics12040733","article-title":"The plasmidomic landscape of clinical methicillin-resistant Staphylococcus aureus isolates from Malaysia","volume":"12","author":"Al-Trad","year":"2023","journal-title":"Antibiotics"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"259","DOI":"10.2147\/IDR.S437920","article-title":"Antimicrobial resistance patterns of Staphylococcus Aureus isolated at a general Hospital in Vietnam between 2014 and 2021","volume":"17","author":"An","year":"2024","journal-title":"Infect Drug Resist."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/1055-7903(92)90021-8","article-title":"Split decomposition: a new and useful approach to phylogenetic analysis of distance data","volume":"1","author":"Bandelt","year":"1992","journal-title":"Mol. 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