An essential periplasmic protein coordinates lipid trafficking and is required for asymmetric polar growth in mycobacteria.

Autor:	Gupta KR; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States., Gwin CM; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States., Rahlwes KC; Department of Microbiology, University of Massachusetts, Amherst, United States., Biegas KJ; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, United States.; Biochemistry, Cell, and Molecular Biology Program, Central Michigan University, Mount Pleasant, United States., Wang C; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States.; Microbial Sciences Institute, Yale University, West Haven, United States., Park JH; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States., Liu J; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States.; Microbial Sciences Institute, Yale University, West Haven, United States., Swarts BM; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, United States.; Biochemistry, Cell, and Molecular Biology Program, Central Michigan University, Mount Pleasant, United States., Morita YS; Department of Microbiology, University of Massachusetts, Amherst, United States., Rego EH; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Nov 08; Vol. 11. Date of Electronic Publication: 2022 Nov 08.
DOI:	10.7554/eLife.80395
Abstrakt:	Mycobacteria, including the human pathogen Mycobacterium tuberculosis , grow by inserting new cell wall material at their poles. This process and that of division are asymmetric, producing a phenotypically heterogeneous population of cells that respond non-uniformly to stress (Aldridge et al., 2012; Rego et al., 2017). Surprisingly, deletion of a single gene - lamA - leads to more symmetry, and to a population of cells that is more uniformly killed by antibiotics (Rego et al., 2017). How does LamA create asymmetry? Here, using a combination of quantitative time-lapse imaging, bacterial genetics, and lipid profiling, we find that LamA recruits essential proteins involved in cell wall synthesis to one side of the cell - the old pole. One of these proteins, MSMEG_0317, here renamed PgfA, was of unknown function. We show that PgfA is a periplasmic protein that interacts with MmpL3, an essential transporter that flips mycolic acids in the form of trehalose monomycolate (TMM), across the plasma membrane. PgfA interacts with a TMM analog suggesting a direct role in TMM transport. Yet our data point to a broader function as well, as cells with altered PgfA levels have differences in the abundance of other lipids and are differentially reliant on those lipids for survival. Overexpression of PgfA, but not MmpL3, restores growth at the old poles in cells missing lamA . Together, our results suggest that PgfA is a key determinant of polar growth and cell envelope composition in mycobacteria, and that the LamA-mediated recruitment of this protein to one side of the cell is a required step in the establishment of cellular asymmetry. Competing Interests: KG, CG, KR, KB, CW, JP, JL, BS, YM, ER No competing interests declared (© 2022, Gupta, Gwin et al.)
Databáze:	MEDLINE
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