Global evolutionary epidemiology, phylogeography and resistome dynamics of Citrobacter species, Enterobacter hormaechei, Klebsiella variicola, and Proteeae clones: A One Health analyses

Abstract

AbstractBackground.The global epidemiology and resistomes dynamics of multidrug-resistant Citrobacter spp., Enterobacter hormaechei, Klebsiella variicola, morganella morganii, Proteus mirabilis and Providencia spp. have not been described, despite their importance as emerging opportunistic clinical pathogens.Methods.The genomes of the above-mentioned organisms were curated from PATRIC and NCBI and used for evolutionary epidemiology, phylogeography and resistome analyses. The phylogeny trees were drawn using RAXmL and edited with Figtree. The resistomes were curated from GenBank and the phylogeography was manually mapped.Results and conclusion.Mcr-9 and other mcr variants were highly prevalent in E. hormaechei subsp. and substantial in C. freundii whilst KPC, OXA-48, NDM, IMP, VIM, TEM, OXA and SHV were abundant in global E. hormaechei subsp., Citrobacter freundii, P. mirabilis, P. stuartii and P. rettgeri clones/clades. Species-specific ampCs were highly conserved in respective species whilst fluoroquinolones, aminoglycosides, macrolides, fosfomycin, chloramphenicol, tetracycline, sulphamethoxazole and trimethoprim resistance mechanisms were abundantly enriched in almost all clades of most of the species, making them extensively and pandrug resistant; K. variicola, C. amalonaticus and C, koseri had relatively few resistance genes. Vertical and horizontal resistome transmissions as well as local and international dissemination of strains evolving from common ancestors were observed, suggesting the anthroponotic, zoonotic, and food-/water-borne infectiousness of these pathogens. There is a global risk of pandrug resistant strains escalating local and international outbreaks of antibiotic-insensitive infections, initiating the dawn of a post-antibiotic era.