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Mycobacterial phenolic glycolipid synthesis is regulated by cAMP-dependent lysine acylation of FadD22
- Authors: Sintu Samanta1, Albel Singh2, Priyanka Biswas3, Apoorva Bhatt4, Sandhya Visweswariah5
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1 1Indian Institute of Science, Bangalore 2 2School of Biosciences, Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK 3 3Indian Institute of Science, Bangalore, India 4 4School of Biosciences, Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK 5 5Indian Institute of Science
- First Published Online: 28 January 2017, Microbiology doi: 10.1099/mic.0.000440
- Issue Published:
The mycobacterial cell envelope is unique in its chemical composition, and has an important role to play in pathogenesis. Phthiocerol dimycocerosates (PDIMs) and glycosylated phenolphthiocerol dimycocerosates, also known as phenolic glycolipids (PGLs), contribute significantly to the virulence of M. tuberculosis. FadD22 is essential for PGL biosynthesis. We have recently shown in vitro that FadD22 is a substrate for lysine acylation by a unique cAMP-dependent, protein lysine acyl transferase found only in mycobacteria. The lysine residue that is acylated is at the active site of FadD22. Therefore, acylation is likely to inhibit FadD22 activity and reduce PGL biosynthesis. Here, we show that PGLs accumulate in a strain of M. bovis BCG deleted for the gene encoding the cAMP-dependent acyl transferase, katbcg, with no change seen in PDIM synthesis. Complementation using KATbcg mutants that are deficient in cAMP-binding or acyl transferase activity, show that PGL accumulation is regulated by cAMP-dependent protein acylation in vivo. Expression of FadD22 and KATbcg mutants in M. smegmatis confirmed that FadD22 is a substrate for lysine acylation by KATbcg. We therefore have described a mechanism by which cAMP can regulate mycobacterial virulence as a result of the ability of this second messenger to modulate critical cell wall components that affect the host immune response.
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/content/journal/micro/10.1099/mic.0.000440.v1dcterms_title-pub_serialIdent:journal/ AND -contentType:BlogPost104
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