Mining of the Novel Virulent ATP-Binding Cassette Importers in by Comparative Genomic Strategy.

The virulent ATP-binding cassette (ABC) importers from , the most common native multidrug resistant and emerging opportunistic pathogen in rapidly growing NTM, were explored by comparative genomic study, in view of the fact that the ABC importers of , responsible for uptaking metals, anions, amino acids, peptides, sugars, and other crucial substances from the host, had been proved to be closely related with the bacillus's virulence, survival in the host macrophages, antibiotic resistance, modulation of host immune system, and so on, although detailed mechanism was unclear. For virulent ABC importers from predicted by orthology and phylogeny analysis of nucleotide-binding domains (NBDs) of , , and , the antibiotic susceptibility of overexpression transformant and knockout mutant was assayed after confirmation by experiment. Three-domain importers were dominant ones in (60.0%), four-domain ones dominant in (87.5%), whereas both types were same in (41.9%). In the phylogenetic tree, the importers of (53.3%) and (62.5%) were mainly distributed in clay A, whereas the clay E was exclusively composed of NBDs, which hinted possible reprogramming of the transporter system during the pathogen evolution. In clay A, and others were predicted virulence-associated because of high sequence similarity to virulence importers. The importance and complexity of antibiotics resistance mechanisms of were pointed out by its overexpression enhancing bacterial resistance to ciprofloxacin, clarithromycin, cefoxitin, and sensitivity to amikacin, and knockout having opposite phenotypes.