title: Mycobacterium tuberculosis CwsA interacts with CrgA and Wag31, and the CrgA-CwsA complex is involved in peptidoglycan synthesis and cell shape determination.
abstract: Bacterial cell division and cell wall synthesis are highly coordinated processes involving multiple proteins. Here, we show that Rv0008c, a novel small membrane protein from Mycobacterium tuberculosis, localizes to the poles and on membranes and shows an overall punctate localization throughout the cell. Furthermore, Rv0008c interacts with two proteins, CrgA and Wag31, implicated in peptidoglycan (PG) synthesis in mycobacteria. Deletion of the Rv0008c homolog in M. smegmatis, MSMEG_0023, caused bulged cell poles, formation of rounded cells, and defects in polar localization of Wag31 and cell wall synthesis, with cell wall synthesis measured by the incorporation of the [(14)C]N-acetylglucosamine cell wall precursor. The M. smegmatis MSMEG_0023 crgA double mutant strain showed severe defects in growth, viability, cell wall synthesis, cell shape, and the localization of the FtsZ, FtsI, and Wag31 proteins. The double mutant strain also exhibited increased autolytic activity in the presence of detergents. Because CrgA and Wag31 proteins interact with FtsI individually, we believe that regulated cell wall synthesis and cell shape maintenance require the concerted actions of the CrgA, Rv0008c, FtsI, and Wag31 proteins. We propose that, together, CrgA and Rv0008c, renamed CwsA for cell wall synthesis and cell shape protein A, play crucial roles in septal and polar PG synthesis and help coordinate these processes with the FtsZ-ring assembly in mycobacteria.
authors.affiliation: The University of Texas Health Science Center at Tyler, Biomedical Research, Tyler, Texas, USA.
authors.forename: P
authors.initials: P
authors.lastname: Plocinski
authors.forename: N
authors.initials: N
authors.lastname: Arora
authors.forename: K
authors.initials: K
authors.lastname: Sarva
authors.forename: E
authors.initials: E
authors.lastname: Blaszczyk
authors.forename: H
authors.initials: H
authors.lastname: Qin
authors.forename: N
authors.initials: N
authors.lastname: Das
authors.forename: R
authors.initials: R
authors.lastname: Plocinska
authors.forename: M
authors.initials: M
authors.lastname: Ziolkiewicz
authors.forename: J
authors.initials: J
authors.lastname: Dziadek
authors.forename: M
authors.initials: M
authors.lastname: Kiran
authors.forename: P
authors.initials: P
authors.lastname: Gorla
authors.forename: T A
authors.initials: TA
authors.lastname: Cross
authors.forename: M
authors.initials: M
authors.lastname: Madiraju
authors.forename: M
authors.initials: M
authors.lastname: Rajagopalan
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism*; D017353:Gene Deletion; D007553:Isotope Labeling; D020102:Mycobacterium smegmatis / Q000166:cytology / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D010457:Peptidoglycan / Q000096:biosynthesis*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002250:Carbon Radioisotopes; C406769:CrgA protein, Neisseria meningitidis; D010457:Peptidoglycan; D014157:Transcription Factors; D000117:Acetylglucosamine