ArticleThe Journal of biological chemistry2012
Phosphorylation of mycobacterial PcaA inhibits mycolic acid cyclopropanation: consequences for intracellular survival and for phagosome maturation block.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- Unravelling the protective effects: PknJ modulates MmaA4 expression and rifampicin susceptibility in Mycobacterium bovis BCG.Archives of microbiology · 2026Article
- The Biosynthetic Pathway of Mycolic Acids: Dual-Function Targets for Tuberculosis Therapeutics and Green Steroid Drugs Biomanufacturing.Pharmaceutics · 2025Review
- Review
- Mapping the phylogeny and lineage history of geographically distinct BCG vaccine strains.Microbial genomics · 2023Article
- Insights into the molecular determinants involved inVirulence · 2021Review
- In-vivo expressed Mycobacterium tuberculosis antigens recognised in three mouse strains after infection and BCG vaccination.NPJ vaccines · 2021Article
- TheFrontiers in cellular and infection microbiology · 2021Article
- An Overview of Genetic Information of Latent Mycobacterium tuberculosis.Tuberculosis and respiratory diseases · 2021Article
- Modulation of the M. tuberculosis cell envelope between replicating and non-replicating persistent bacteria.Tuberculosis (Edinburgh, Scotland) · 2020Review
- The protein kinase PknB negatively regulates biosynthesis and trafficking of mycolic acids in mycobacteria.Journal of lipid research · 2020Article
- Protein kinases PknA and PknB independently and coordinately regulate essential Mycobacterium tuberculosis physiologies and antimicrobial susceptibility.PLoS pathogens · 2020Article
- The mycobacterial cell envelope - a moving target.Nature reviews. Microbiology · 2020Review
- LipidII interaction with specific residues of Mycobacterium tuberculosis PknB extracytoplasmic domain governs its optimal activation.Nature communications · 2019Article
- Impact of the epoxide hydrolase EphD on the metabolism of mycolic acids in mycobacteria.The Journal of biological chemistry · 2018Article
- Epigenetic Phosphorylation Control of Mycobacterium tuberculosis Infection and Persistence.Microbiology spectrum · 2017Review
- Endogenous and Exogenous KdpF Peptide Increases Susceptibility ofFrontiers in cellular and infection microbiology · 2017Article
- The distinct fate of smooth and rough Mycobacterium abscessus variants inside macrophages.Open biology · 2016Article
- Ser/Thr Phosphorylation Regulates the Fatty Acyl-AMP Ligase Activity of FadD32, an Essential Enzyme in Mycolic Acid Biosynthesis.The Journal of biological chemistry · 2016Article
- Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Evolution of Mycolic Acid Biosynthesis Genes and Their Regulation during Starvation in Mycobacterium tuberculosis.Journal of bacteriology · 2015Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pathogenic mycobacteria survive within macrophages by residing in phagosomes, which they prevent from maturing and fusing with lysosomes. Although several bacterial components were seen to modulate phagosome processing, the molecular regulatory mechanisms taking part in this process remain elusive. We investigated whether the phagosome maturation block (PMB) could be modulated by signaling through Ser/Thr phosphorylation. Here, we demonstrated that mycolic acid cyclopropane synthase PcaA, but not MmaA2, was phosphorylated by mycobacterial Ser/Thr kinases at Thr-168 and Thr-183 both in vitro and in mycobacteria. Phosphorylation of PcaA was associated with a significant decrease in the methyltransferase activity, in agreement with the strategic structural localization of these two phosphoacceptors. Using a BCG ΔpcaA mutant, we showed that PcaA was required for intracellular survival and prevention of phagosome maturation in human monocyte-derived macrophages. The physiological relevance of PcaA phosphorylation was further assessed by generating PcaA phosphoablative (T168A/T183A) or phosphomimetic (T168D/T183D) mutants. In contrast to the wild-type and phosphoablative pcaA alleles, introduction of the phosphomimetic pcaA allele in the ΔpcaA mutant failed to restore the parental mycolic acid profile and cording morphotype. Importantly, the PcaA phosphomimetic strain, as the ΔpcaA mutant, exhibited reduced survival in human macrophages and was unable to prevent phagosome maturation. Our results add new insight into the importance of mycolic acid cyclopropane rings in the PMB and provide the first evidence of a Ser/Thr kinase-dependent mechanism for modulating mycolic acid composition and PMB.
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