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Mycobacterial fatty acid catabolism is repressed by FdmR to sustain lipogenesis and virulence

ABSTRACT: Here, we identified a long-chain acyl-CoA-responsive transcriptional repressor, FdmR, as the key regulator of mycobacterial fatty acid catabolism. We employed ChIP-Seq to identify the genomic binding regions for FdmR. FdmR was found to bind upstream of fadA2, fabG4, fadE24, fixA, MMAR_1683, fadE5, icl, desA3, desA3_1, and MMAR_2730.We then demonstrated that FdmR acts as a valve to direct the fatty acid flux from β-oxidation towards lipid biosynthesis, thereby avoiding the overactive catabolism and accumulation of biologically toxic intermediates. This regulatory mechanism enables a high rate of cell growth with modest consumption of fatty acid substrates.

ORGANISM(S): Mycobacterium marinum

PROVIDER: GSE156432 | GEO | 2021/03/01

REPOSITORIES: GEO

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Project description:Background: Inner Mongolia is a major raw-cashmere-producing province in China, Inner Mongolia cashmere goat harbors three types —Erlangshan, Aerbasi and Alashan. Nearly 700,000 Aerbasi cashmere goats are fed per year, and meat production is nearly 10,000 tons. However, there are no reports on the meat of this goat. To better understand the molecular variations underlying intramuscular fat (IMF) anabolism and catabolism in Inner Mongolian cashmere goat, the proteomic differences between the biceps femoris (BF) and longissimus dorsi (LD) were investigated by label-free strategy. Then, the proteins were verified by western blot analysis as being involved in IMF anabolism and catabolism. Results: The IMF content was significantly higher in the BF than in the LD, suggesting that IMF is accumulated more in the BF or metabolized more in the LD. We performed proteomic analysis of IMF anabolism and catabolism at the proteomic level, and 1209 proteins were identified in the BF (high-IMF) and LD (low-IMF) groups, with 993 and 896 proteins in each group. Among them, 110 were differentially expressed proteins (DEPs). Gene ontology (GO) classification statistics showed that the 110 DEPs were functionally classified into 100 annotation clusters. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that three pathways were related to IMF metabolism and deposition—fatty acid metabolism, fatty acid degradation and fatty acid elongation—and included 7 proteins. Conclusion: GO and KEGG analyses showed that differentially expressed HADHA, HADHB, ACSL1, ACADS, ACAT1 and ACAA2 in the mitochondrion act via fatty acid metabolism, fatty acid degradation and fatty acid elongation to influence the metabolism and synthesis of long-, short- and medium-chain fatty acids and influence IMF anabolism and catabolism. Protein-protein interaction (PPI) network analysis showed that IMF accumulation in different muscle tissues of Aerbasi cashmere goat was affected by not only 5 key enzymes or proteins involved in fatty acid synthesis and metabolism but also 5 DEPs (SUCLG1, SUCLG2, CS, DLST, ACO2) in the TCA cycle. Our results provide new insights into IMF deposition in goat and improve our understanding of the molecular mechanisms underlying IMF anabolism and catabolism.

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Mycobacterial fatty acid catabolism is repressed by FdmR to sustain lipogenesis and virulence

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