Characterization of a Mycobacterium avium subsp. avium Operon Associated with Virulence and Drug Detoxification

MARIANA NOELIA VIALE,; KUN TAEK PARK,; BELÉN IMPERIALE,; ANDREA KARINA GIOFFRE,; MARÍA ALEJANDRA COLOMBATTI OLIVIERI,; ROBERTO DAMIÁN MOYANO; NORA MORCILLO; MARÍA DE LA PAZ SANTANGELO,; WILLIAM DAVIS,; MARIA ISABEL ROMANO

BioMed Research International

HINDAWI PUBLISHING CORPORATION

Lugar: New York; Año: 2014

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 againstmycobacteria.Theknockoutmutation of this operon severely reduces the replication of bothmycobacterial species during infection in mice and increases susceptibility to toxic compounds. In order to gain insight into the function of LprG in the Mycobacteriumaviumcomplex, in this study, we assayed the effect of the deletion of lprGgene in theD4ERstrainof 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.