Phylogeny of transferable oxazolidinone resistance genes and homologs

Abstract

Abstract This study aims at delving into the phylogenetic origin of transmissible oxazolidinones resistance mechanisms conferring cross-resistance to other drugs of human and veterinary importance. Amino acid sequences of the five cfr ribosome methylases, optrA and poxtA proteins were used as queries in search against 219549 bacterial genomes in the NCBI RefSeq database. Hits with > 40% amino acid identity and > 80% query coverage were aligned and phylogenetic trees were reconstructed. All five cfr genes produced very similar trees, with rlmN housekeeping ribosome methylases basal to sister groups of S-adenosyl-methionine dependent methyltransferases from Deltaproteobacteria and Actinomycetia, including antibiotic producer Streptomyces and of the monophyletic group of cfr proteins. Basal branches from the latter contained paenibacilli and other soil bacteria; then split to the clades [cfr(C):cfr(E)] and [[cfr:cfr(B)]:cfr(D)], always with various Bacillaceae in their stems. Lachnospiraceae were encountered in basal branches of both optrA and poxtA trees. The ultimate origin of cfr genes is rlmN housekeeping methylases, which evolved into a suicide-avoiding methylase in antibiotic producers; a soil organism (Lachnospiraceae, Paenibacilli) acted probably as agent of transfer into pathogens. In case of optrA, the porcine pathogenic Streptococcus suis was present in all branches, while closest to poxtA were proteins from Clostridia.