Viale Mariana Noelia, Park Kun Taek, Imperiale Belén, Gioffre Andrea Karina, Colombatti Olivieri María Alejandra, Moyano Roberto Damián, Morcillo Nora, Santangelo María de la Paz, Davis William, Romano María Isabel
Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria, Hurlingham, Buenos Aires 1686, Argentina.
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Biomed Res Int. 2014;2014:809585. doi: 10.1155/2014/809585. Epub 2014 May 20.
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.
结核分枝杆菌和牛分枝杆菌的lprG-p55操纵子参与有毒化合物的转运。P55是一种外排泵，可提供对多种药物的抗性，而LprG是一种脂蛋白，可调节宿主针对分枝杆菌的免疫反应。该操纵子的敲除突变会严重降低两种分枝杆菌在小鼠感染期间的复制，并增加对有毒化合物的易感性。为了深入了解LprG在鸟分枝杆菌复合群中的功能，在本研究中，我们检测了鸟分枝杆菌亚种鸟分枝杆菌D4ER菌株中lprG基因缺失的影响。用潮霉素盒替换lprG基因对p55的表达产生了极性效应。此外，观察到突变菌株对溴化乙锭的敏感性降低了两倍，并且对利福平、阿米卡星、利奈唑胺和利福布汀等抗生素的抗性受损。此外，该突变降低了细菌在体外巨噬细胞和体内小鼠模型中的毒力。这些发现清楚地表明，功能性LprG和P55对于有毒化合物的正确转运以及鸟分枝杆菌亚种鸟分枝杆菌在体外和体内的存活是必要的。
