title: Characterization of a Mycobacterium avium subsp. avium operon associated with virulence and drug detoxification.
abstract: The lprG-p55 operon of Mycobacterium tuberculosis and Mycobacterium bovis is involved in the transport of toxic compounds. P55 is an efflux pump that provides resistance to several drugs, while LprG is a lipoprotein that modulates the host's immune response against mycobacteria. The knockout mutation of this operon severely reduces the replication of both mycobacterial species during infection in mice and increases susceptibility to toxic compounds. In order to gain insight into the function of LprG in the Mycobacterium avium complex, in this study, we assayed the effect of the deletion of lprG gene in the D4ER strain of Mycobacterium avium subsp. avium. The replacement of lprG gene with a hygromycin cassette caused a polar effect on the expression of p55. Also, a twofold decrease in ethidium bromide susceptibility was observed and the resistance to the antibiotics rifampicin, amikacin, linezolid, and rifabutin was impaired in the mutant strain. In addition, the mutation decreased the virulence of the bacteria in macrophages in vitro and in a mice model in vivo. These findings clearly indicate that functional LprG and P55 are necessary for the correct transport of toxic compounds and for the survival of MAA in vitro and in vivo.
authors: Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria, Hurlingham, Buenos Aires 1686, Argentina.
authors: Mariana Noelia
authors: MN
authors: Viale
authors: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
authors: Kun Taek
authors: 0000-0001-6177-0373
authors: KT
authors: Park
authors: Laboratorio de Referencia en el Control de la Tuberculosis, Hospital Dr. Antonio A. Cetrángolo, Vicente López, Buenos Aires 8185, Argentina.
authors: Belén
authors: B
authors: Imperiale
authors: Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria, Hurlingham, Buenos Aires 1686, Argentina.
authors: Andrea Karina
authors: AK
authors: Gioffre
authors: Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria, Hurlingham, Buenos Aires 1686, Argentina.
authors: María Alejandra
authors: MA
authors: Colombatti Olivieri
authors: Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria, Hurlingham, Buenos Aires 1686, Argentina.
authors: Roberto Damián
authors: RD
authors: Moyano
authors: Laboratorio de Referencia en el Control de la Tuberculosis, Hospital Dr. Antonio A. Cetrángolo, Vicente López, Buenos Aires 8185, Argentina.
authors: Nora
authors: N
authors: Morcillo
authors: Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria, Hurlingham, Buenos Aires 1686, Argentina.
authors: María de la Paz
authors: Mde L
authors: Santangelo
authors: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
authors: William
authors: W
authors: Davis
authors: Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria, Hurlingham, Buenos Aires 1686, Argentina.
authors: María Isabel
authors: MI
authors: Romano
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics; D009162:Mycobacterium avium / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D009876:Operon; D014376:Tuberculosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000662:veterinary; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D008074:Lipoproteins; D037521:Virulence Factors