Genomic landscape of antimicrobial resistance genes in Bacillus anthracis

Abstract Detection of antimicrobial resistance (AMR) is critical for an effective public health response to anthrax, but a complete catalog of AMR markers in Bacillus anthracis is lacking. Here we characterized the landscape of AMR-associated B. anthracis genes using complete CDC and public genomes (NCBI RefSeq, SRA). We identified 33 candidate AMR genes from literature analysis and AMR gene databases, and surveyed them for variants. All predicted AMR genes were chromosomal; twenty were relevant to antibiotics recommended for anthrax treatment, while 13 were associated with other antibiotics. Across candidates, conventional broth microdilution susceptibility testing only confirmed penicillin resistance (linked to sigP , rsiP variants). As expected, few markers predicted functional resistance since AMR in B. anthracis is exceedingly rare. Variant frequencies were generally low, but slightly higher in genes presumptively linked to tetracycline-, penicillin-, and macrolide-resistance. Variation across all 33 regions is reported and intended to establish non-AMR conferring natural variation across the sample sets. The results from this study were integrated in a previously published bioinformatics pipeline, PiMA, expanding the set of genes analyzed as well as providing context for natural variation unlikely to confer AMR phenotypes. While B. anthracis is largely clonal with limited genetic variation, the AMR gene catalog linked to functional susceptibility results offers a valuable, evidence-based resource that strengthens resistance prediction and anthrax readiness.