Abstract
Identifying and characterizing the individual contributors to bacterial cellular elongation and division will improve our understanding of their impact on cell growth and division. Here, we delineated the role of ftsQ, a terminal gene of the highly conserved division cell wall (dcw) operon, in growth, survival, and cell length maintenance in the human pathogen Mycobacterium tuberculosis (Mtb). We found that FtsQ overexpression significantly increases the cell length and number of multiseptate cells. FtsQ depletion in Mtb resulted in cells that were shorter than WT cells during the initial growth stages (4 days after FtsQ depletion) but were longer than WT cells at later stages (10 days after FtsQ depletion) and compromised the survival in vitro and in differentiated THP1 macrophages. Overexpression of N- and C-terminal FtsQ regions altered the cell length, and the C-terminal domain alone complemented the FtsQ depletion phenotype. MS analyses suggested robust FtsQ phosphorylation on Thr-24, and although phosphoablative and -mimetic mutants rescued the FtsQ depletion-associated cell viability defects, they failed to complement the cell length defects. MS and coimmunoprecipitation experiments identified 63 FtsQ-interacting partners, and we show that the interaction of FtsQ with the recently identified cell division protein SepIVA is independent of FtsQ phosphorylation and suggests a role of FtsQ in modulating cell division. FtsQ exhibited predominantly septal localization in both the presence and absence of SepIVA. Our results suggest a role for FtsQ in modulating the length, division, and survival of Mtb cells both in vitro and in the host.
Highlights
Identifying and characterizing the individual contributors to bacterial cellular elongation and division will improve our understanding of their impact on cell growth and division
MS and coimmunoprecipitation experiments identified 63 FtsQ-interacting partners, and we show that the interaction of FtsQ with the recently identified cell division protein SepIVA is independent of FtsQ phosphorylation and suggests a role of FtsQ in modulating cell division
Mycobacterium smegmatis (Msmeg) was electroporated with either pNit1 or pNit-FtsQ construct wherein ftsQ is cloned under the isovaleronitrile (IVN)-inducible promoter
Summary
Identifying and characterizing the individual contributors to bacterial cellular elongation and division will improve our understanding of their impact on cell growth and division. Proto-ring proteins FtsZ, FtsA, and ZipA are the early recruits to the divisome and ensure constriction initiation and its stabilization [10] This is followed by recruitment of FtsK, FtsQ in complex with FtsB and FtsL (FtsQBL), peptidoglycan remodelers such as FtsW (transglycosylase), FtsI (transpeptidase), FtsN, carboxypeptidases, endopeptidases, and a number of other accessory proteins, which are necessary for chromosome segregation and final cytokinesis [11,12,13,14,15,16,17]. Homologs of FtsZ, FtsK, FtsB, FtsL FtsQ, FtsI, and FtsW are annotated in mycobacteria, homologs for FtsA, ZipA, and FtsN proteins found in E. coli are lacking [23, 24] The presence of these homologous proteins and a similar sequence of recruitment at the midcell suggest the partial preservation of elementary complexes and their functions in mycobacteria [24]. A homolog of FtsK in Mycobacterium smegmatis (Msmeg) plays a
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