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

Area of Science:

• Microbiology
• Immunology
• Molecular Biology

Background:

• The lprG-p55 operon in Mycobacterium tuberculosis and bovis facilitates toxic compound transport and influences host immune response.
• P55 acts as an efflux pump conferring drug resistance, while LprG is a lipoprotein modulating host immunity.
• Operon knockout mutations reduce mycobacterial replication and increase susceptibility to toxins.

Purpose of the Study:

• To investigate the role of the lprG gene in the virulence and drug resistance of Mycobacterium avium subsp. avium (MAA).
• To understand the function of LprG in the context of the Mycobacterium avium complex.

Main Methods:

• Deletion of the lprG gene in the D4ER strain of MAA using a hygromycin cassette.
• Assaying the effect of gene deletion on p55 expression, ethidium bromide susceptibility, and resistance to antibiotics (rifampicin, amikacin, linezolid, rifabutin).
• Evaluating bacterial virulence in vitro using macrophages and in vivo using a mouse model.

Main Results:

• Deletion of lprG caused a polar effect on p55 expression.
• The mutant strain showed a twofold decrease in ethidium bromide susceptibility.
• Antibiotic resistance to rifampicin, amikacin, linezolid, and rifabutin was impaired in the mutant.
• MAA virulence was reduced in both in vitro macrophage assays and in vivo mouse models.

Conclusions:

• Functional LprG and P55 are essential for the proper transport of toxic compounds in MAA.
• The lprG-p55 operon plays a critical role in MAA survival and virulence both in vitro and in vivo.
• Targeting the lprG-p55 operon could be a potential strategy to combat MAA infections.