title: Insights into the function of FhaA, a cell division-associated protein in mycobacteria.
abstract: FhaA is a forkhead-associated domain-containing protein, the depletion of which leads to accumulation of peptidoglycan (PG) precursors at the septum and poles in Mycobacterium smegmatis (M. smegmatis), by a mechanism undefined thus far. To elucidate its function, we constructed an fhaA (MSMEG_0035) knockout (ΔfhaA) strain in M. smegmatis and demonstrated that this gene is dispensable for in vitro growth. The mutant showed a short cell length phenotype due to a probable defect in cell elongation/cell wall synthesis, which was reversed by complementation with both M. smegmatis and Mycobacterium tuberculosis (M. tb) fhaA (Rv0020c), confirming their association with the observed phenotype. The identification of penicillin binding protein A (PbpA), a PG biosynthesis enzyme as an interacting partner for mycobacterial FhaA, provided a hint into the functioning of FhaA. A drastic reduction in the levels of ectopically expressed PbpA in the ΔfhaA mutant vs wild-type M. smegmatis suggested that FhaA interacts with and stabilises PbpA. In addition, the fhaA deletion mutant was sensitive to multiple classes of antibiotics pointing to a general permeability defect. Our findings uncover a role for FhaA in PG biosynthesis and suggest its involvement in the maintenance of mycobacterial cell envelope integrity.
authors.forename: Gopinath
authors.initials: G
authors.lastname: Viswanathan
authors.forename: Sangya
authors.initials: S
authors.lastname: Yadav
authors.forename: Shrilaxmi V
authors.initials: SV
authors.lastname: Joshi
authors.forename: Tirumalai R
authors.initials: TR
authors.lastname: Raghunand
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002473:Cell Wall / Q000378:metabolism; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D046915:Penicillin-Binding Proteins / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping
chemical_list: D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan
keywords: FhaA, PbpA; Mycobacterium smegmatis; Mycobacterium tuberculosis; cell envelope; peptidoglycan