title: Novel role of phosphorylation-dependent interaction between FtsZ and FipA in mycobacterial cell division.
abstract: The bacterial divisome is a multiprotein complex. Specific protein-protein interactions specify whether cell division occurs optimally, or whether division is arrested. Little is known about these protein-protein interactions and their regulation in mycobacteria. We have investigated the interrelationship between the products of the Mycobacterium tuberculosis gene cluster Rv0014c-Rv0019c, namely PknA (encoded by Rv0014c) and FtsZ-interacting protein A, FipA (encoded by Rv0019c) and the products of the division cell wall (dcw) cluster, namely FtsZ and FtsQ. M. smegmatis strains depleted in components of the two gene clusters have been complemented with orthologs of the respective genes of M. tuberculosis. Here we identify FipA as an interacting partner of FtsZ and FtsQ and establish that PknA-dependent phosphorylation of FipA on T77 and FtsZ on T343 is required for cell division under oxidative stress. A fipA knockout strain of M. smegmatis is less capable of withstanding oxidative stress than the wild type and showed elongation of cells due to a defect in septum formation. Localization of FtsQ, FtsZ and FipA at mid-cell was also compromised. Growth and survival defects under oxidative stress could be functionally complemented by fipA of M. tuberculosis but not its T77A mutant. Merodiploid strains of M. smegmatis expressing the FtsZ(T343A) showed inhibition of FtsZ-FipA interaction and Z ring formation under oxidative stress. Knockdown of FipA led to elongation of M. tuberculosis cells grown in macrophages and reduced intramacrophage growth. These data reveal a novel role of phosphorylation-dependent protein-protein interactions involving FipA, in the sustenance of mycobacterial cell division under oxidative stress.
authors.affiliation: Department of Chemistry, Bose Institute, Kolkata, India.
authors.forename: Kamakshi
authors.initials: K
authors.lastname: Sureka
authors.forename: Tofajjen
authors.initials: T
authors.lastname: Hossain
authors.forename: Partha
authors.initials: P
authors.lastname: Mukherjee
authors.forename: Paramita
authors.initials: P
authors.lastname: Chatterjee
authors.forename: Pratik
authors.initials: P
authors.lastname: Datta
authors.forename: Manikuntala
authors.initials: M
authors.lastname: Kundu
authors.forename: Joyoti
authors.initials: J
authors.lastname: Basu
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D009161:Mycobacterium / Q000166:cytology* / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D011485:Protein Binding; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria