title: The ABC transporter YejABEF is required for resistance to antimicrobial peptides and the virulence of Brucella melitensis.
abstract: The ability to resist the killing effects of host antimicrobial peptides (AMPs) plays a vital role in the virulence of pathogens. The Brucella melitensis NI genome has a gene cluster that encodes ABC transport. In this study, we constructed yejA1, yejA2, yejB, yejE, yejF, and whole yej operon deletion mutants, none of which exhibited discernible growth defect in TSB or minimal medium. Unlike their parental strain, the mutants showed a significantly increased sensitivity to acidic stress. The NIΔyejE and NIΔyejABEF mutants were also more sensitive than B. melitensis NI to polymyxin B, and the expression of yej operon genes was induced by polymyxin B. Moreover, cell and mouse infection assays indicated that NIΔyejE and NIΔyejABEF have restricted invasion and replication abilities inside macrophages and are rapidly cleared from the spleens of infected mice. These findings indicate that the ABC transporter YejABEF is required for the virulence of Brucella, suggesting that resistance to host antimicrobials is a key mechanism for Brucella to persistently survive in vivo. This study provided insights that led us to further investigate the potential correlation of AMP resistance with the mechanisms of immune escape and persistent infection by pathogens.
authors.affiliation: Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Bie
authors.affiliation: Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Buyun
authors.initials: B
authors.lastname: Cui
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D017347:Brucella melitensis / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D002006:Brucellosis / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005260:Female; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008807:Mice, Inbred BALB C; D009876:Operon; D014774:Virulence / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins