Genetic Determinants of Antibiotic Resistance in Francisella

Tularemia, caused by Francisella tularensis, 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). Francisella 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 Francisella 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 Francisella. 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 Francisella. We discuss newly developed methods of testing antibiotics against Francisella which involve the intracellular nature of Francisella infection and may better reflect the eventual clinical outcomes for new antibiotic compounds. Understanding the genetically encoded determinants of AMR in Francisella is key to optimizing the treatment of patients and potentially developing new antimicrobials for this dangerous intracellular pathogen.

Automated summary

Tularemia caused by Francisella tularensis has been historically developed into a biological weapon. In order to optimize patient treatment and potentially develop new antimicrobials, understanding the genetically encoded determinants of antibiotic resistance in Francisella is crucial. Research has been conducted on both the experimental and bioinformatic aspects of antibiotic resistance in Francisella, as well as the difference in phenotypic resistance between planktonic and biofilm forms of the bacteria.