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Identification of residues important for M. tuberculosis MmpL11 function reveals that function is modulated by phosphorylation in the C‐terminal domain
Author(s) -
Melly Geoff C.,
Stokas Haley,
Davidson Patrick M.,
Roma José Santinni,
Rhodes Heather L.,
Purdy Georgiana E.
Publication year - 2021
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14611
Subject(s) - biology , cell envelope , periplasmic space , biochemistry , atp binding cassette transporter , mycobacterium tuberculosis , biogenesis , mycobacterium smegmatis , virulence , microbiology and biotechnology , transporter , tuberculosis , gene , medicine , escherichia coli , pathology
The Mycobacterium tuberculosis cell envelope is a critical interface between the host and pathogen and provides a protective barrier against the immune response and antibiotics. Cell envelope lipids are also mycobacterial virulence factors that influence the host immune response. The mycobacterial membrane protein large (MmpL) proteins transport cell envelope lipids and siderophores that are important for the basic physiology and pathogenesis of M. tuberculosis . We recently identified MmpL11 as a conserved transporter of mycolic acid‐containing lipids including monomeromycolyl diacylglycerol (MMDAG), mycolate wax ester (MWE), and long‐chain triacylglycerols (LC‐TAGs). These lipids contribute to biofilm formation in M. tuberculosis and M. smegmatis , and non‐replicating persistence in M. tuberculosis . In this report, we identified domains and residues that are essential for MmpL11 TB lipid transporter activity. Specifically, we show that the D1 periplasmic loop and a conserved tyrosine are essential for the MmpL11 function. Intriguingly, we found that MmpL11 levels are regulated by the phosphorylation of threonine in the cytoplasmic C‐terminal domain, providing the first direct evidence of the phospho‐regulation of MmpL11 transporter activity in M. tuberculosis and M. smegmatis . Our results offer further insight into the function of MmpL transporters and regulation of mycobacterial cell envelope biogenesis.