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.

Biofilm architecture: An emerging synthetic biology target.

Synthetic biologists are exploiting biofilms as an effective mechanism for producing various outputs. Metabolic optimization has become commonplace as a method of maximizing system output. In addition to production pathways, the biofilm itself contributes to the efficacy of production. The purpose of this review is to highlight opportunities that might be leveraged to further enhance production in preexisting biofilm production systems. These opportunities may be used with previously established production systems as a method of improving system efficiency further. This may be accomplished through the reduction in the cost of establishing and maintaining biofilms, and maintenance of the enhancement of product yield per unit of time, per unit of area, or per unit of required input.