Characterization of a Mycobacterium avium subsp. avium operon associated with virulence and drug detoxification

VIALE MN; PARK KT; IMPERIALE BELÉN; GIOFFRÉ ANDREA; COLOMBATI OLIVIERI MA; MOYANO RD; MORCILLO N; SANTANGELO M DE L; DAVIS W; ROMANO MI

BioMed Research International

Hindawi Publishing Corporation

Año: 2014

2314-6133

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 aviumcomplex, in this study, we assayed the effect of the deletion oflprG gene in the D4ER strain ofMycobacterium aviumsubsp. avium. The replacement oflprG 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 macrophagesin 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 MAAin vitro and in vivo