Mycolic acids are unique long chain fatty acids found in the lipid-rich cell walls of mycobacteria including the tubercle bacillus Mycobacterium tuberculosis. Essential for viability and virulence, enzymes involved in the biosynthesis of mycolic acids represent novel targets for drug development. This is particularly relevant to the impact on global health given the rise of multidrug resistant and extensively drug resistant strains of M. tuberculosis. In this review, we discuss recent advances in our understanding of how mycolic acid are synthesised, especially the potential role of specialised fatty acid synthase complexes. Also, we examine the role of a recently reported mycolic acid transporter MmpL3 with reference to several reports of the targeting of this transporter by diverse compounds with anti-M. tuberculosis activity. Additionally, we consider recent findings that place mycolic acid biosynthesis in the context of the cell biology of the bacterium, viz its localisation and co-ordination with the bacterial cytoskeleton, and its role beyond maintaining cell envelope integrity.
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http://dx.doi.org/10.1111/mmi.13101 | DOI Listing |
Int J Syst Evol Microbiol
January 2025
International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.
Four novel nontuberculous mycobacteria were discovered from a historical strain collection at the International Reference Laboratory of Mycobacteriology at Statens Serum Institut in Copenhagen, Denmark. Phylogenetic analysis combining the 16S , internal transcribed spacer and 23S elements, as well as a single-copy core-gene (, , and ) analysis of these freeze-dried mycobacteria, clinically isolated from gastric lavage samples between 1948 and 1955, showed to be associated with type strains grouping within the Terra and Fortuitum-Vaccae clade. Phenotypic characteristics, biochemical properties and fatty acid and mycolic acid profiles supported the classification as novel strains.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
(Mtb) is a leading cause of death, with an escalating global occurrence of drug-resistant infections that are partially attributed to cell wall mycolic acids derived from type II fatty acid biosynthesis (FAS-II). Here, the central acyl carrier protein, AcpM, contributes to the regulation of complex and specific protein-protein interactions (PPIs), though the orchestration of these events remain largely unresolved due to unique features of AcpM. Limitations include complexities in generating modified AcpM in a single state.
View Article and Find Full Text PDFHeliyon
November 2024
Unit of Microbiology, Bioorganic and Macromolecular Chemistry, Department of Research in Drug Development, Faculty of Pharmacy, Université Libre de Bruxelles, Belgium.
MabR (), a PucR-type transcription factor, plays a crucial role in regulating mycolic acid biosynthesis in . To understand its regulatory mechanisms, we determined the crystal structures of its N-terminal and C-terminal domains. The N-terminal domain adopts a globin-like fold, while the C-terminal domain comprises an α/β GGDEF domain and an all-α effector domain with a helix-turn-helix DNA-binding motif.
View Article and Find Full Text PDFTrop Med Infect Dis
November 2024
Future Production: Chemicals, Council for Scientific and Industrial Research, Pretoria 0081, South Africa.
Microb Pathog
January 2025
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India. Electronic address:
Tuberculosis continues to pose a health challenge causing the loss of millions of lives despite the existence of multiple drugs, for treatment. The emergence of drug-resistant strains has made the situation more complex making it increasingly difficult to fight against this disease. This review outlines the challenges associated with TB drug discovery, the nature of Mycobacterium tuberculosis shedding light on the mechanisms that lead to treatment failure and antibiotic resistance.
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