{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:15:05Z","timestamp":1790511305032,"version":"4.1.0"},"reference-count":193,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"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":"<jats:p>Tularemia, caused by<jats:italic>Francisella tularensis<\/jats:italic>, is endemic to the northern hemisphere. This zoonotic organism has historically been developed into a biological weapon. For this Tier 1, Category A select agent, it is important to expand our understanding of its mechanisms of antibiotic resistance (AMR).<jats:italic>Francisella<\/jats:italic>is unlike many Gram-negative organisms in that it does not have significant plasmid mobility, and does not express AMR mechanisms on plasmids; thus plasmid-mediated resistance does not occur naturally. It is possible to artificially introduce plasmids with AMR markers for cloning and gene expression purposes. In this review, we survey both the experimental research on AMR in<jats:italic>Francisella<\/jats:italic>and bioinformatic databases which contain genomic and proteomic data. We explore both the genetic determinants of intrinsic AMR and naturally acquired or engineered antimicrobial resistance as well as phenotypic resistance in<jats:italic>Francisella<\/jats:italic>. Herein we survey resistance to beta-lactams, monobactams, carbapenems, aminoglycosides, tetracycline, polymyxins, macrolides, rifampin, fosmidomycin, and fluoroquinolones. We also highlight research about the phenotypic AMR difference between planktonic and biofilm<jats:italic>Francisella.<\/jats:italic>We discuss newly developed methods of testing antibiotics against<jats:italic>Francisella<\/jats:italic>which involve the intracellular nature of<jats:italic>Francisella<\/jats:italic>infection and may better reflect the eventual clinical outcomes for new antibiotic compounds. Understanding the genetically encoded determinants of AMR in<jats:italic>Francisella<\/jats:italic>is key to optimizing the treatment of patients and potentially developing new antimicrobials for this dangerous intracellular pathogen.<\/jats:p>","DOI":"10.3389\/fmicb.2021.644855","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T04:21:01Z","timestamp":1620793261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Genetic Determinants of Antibiotic Resistance in Francisella"],"prefix":"10.3389","volume":"12","author":[{"given":"Stephen J.","family":"Kassinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique L.","family":"van Hoek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0140-6736(00)72122-2","article-title":"Further observations on penicillin.","volume":"238","author":"Abraham","year":"1941","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3118","DOI":"10.1128\/IAI.00146-10","article-title":"Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster.","volume":"78","author":"Ahlund","year":"2010","journal-title":"Infect. 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