The Non-Essential Mycolic Acid Biosynthesis Genes hadA and hadC Contribute to the Physiology and Fitness of Mycobacterium smegmatis

• Published in: PloS one Vol. 10; no. 12; p. e0145883
• Main Authors: Jamet, Stevie, Slama, Nawel, Domingues, Joana, Laval, Françoise, Texier, Pauline, Eynard, Nathalie, Quémard, Annaik, Peixoto, Antonio, Lemassu, Anne, Daffé, Mamadou, Cam, Kaymeuang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23-12-2015; Public Library of Science (PLoS)
• Subjects: Antibiotics; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biochemistry, Molecular Biology; Biofilms; Biosynthesis; Biotechnology; Cell Survival; Clonal deletion; Deactivation; Dehydration; Deoxyribonucleic acid; DNA; Drugs; Etiology; Fatty acids; Fatty-acid synthase; Fitness; Genes; Glycerol; High temperature; Inactivation; Life Sciences; Microbial Sensitivity Tests; Microbiology and Parasitology; Mutants; Mycobacterium Infections, Nontuberculous - metabolism; Mycobacterium Infections, Nontuberculous - microbiology; Mycobacterium smegmatis; Mycobacterium smegmatis - physiology; Mycobacterium tuberculosis; Mycolic acids; Mycolic Acids - metabolism; Permeability; Physiological aspects; Physiology; Plasmids; Proteins; Tuberculosis; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0145883

Gram positive mycobacteria with a high GC content, such as the etiological agent of tuberculosis Mycobacterium tuberculosis, possess an outer membrane mainly composed of mycolic acids (MAs), the so-called mycomembrane, which is essential for the cell. About thirty genes are involved in the biosynthesis of MAs, which include the hadA, hadB and hadC genes that encode the dehydratases Fatty Acid Synthase type II (FAS-II) known to function as the heterodimers HadA-HadB and HadB-HadC. The present study shows that M. smegmatis cells remain viable in the absence of either HadA and HadC or both. Inactivation of HadC has a dramatic effect on the physiology and fitness of the mutant strains whereas that of HadA exacerbates the phenotype of a hadC deletion. The hadC mutants exhibit a novel MA profile, display a distinct colony morphology, are less aggregated, are impaired for sliding motility and biofilm development and are more resistant to detergent. Conversely, the hadC mutants are significantly more susceptible to low- and high-temperature and to selective toxic compounds, including several current anti-tubercular drugs.