The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division

Dasgupta, Arunava; Datta, Pran K.; Kundu, Manikuntala; Basu, Joyoti

doi:10.1099/mic.0.28630-0

Cited by 146 publications

(122 citation statements)

References 58 publications

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“…We found strong CrgA interactions with FtsQ, PBPA, and FtsI. The latter two proteins are predicted to be transpeptidases involved in peptidoglycan cross-linking during septum synthesis (12,14). FtsQ is an integral part of the divisome and is believed to play a crucial role in the recruitment of early and late cell division proteins and peptidoglycan polymerases (4,23,51).…”

Section: Discussionmentioning

confidence: 97%

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Characterization of CrgA, a New Partner of the Mycobacterium tuberculosis Peptidoglycan Polymerization Complexes

et al. 2011

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Section: Discussionmentioning

confidence: 97%

“…Next, we examined whether CrgA interacted with the previously identified cell division proteins, FtsI, FtsQ, ClpX, SepF, PBPA, and RodA, using BACTH assays (12,14,20,45). This analysis demonstrated CrgA interactions with FtsI, FtsQ, and PBPA but not with RodA, ClpX, or SepF ( Fig.…”

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confidence: 99%

Characterization of CrgA, a New Partner of the Mycobacterium tuberculosis Peptidoglycan Polymerization Complexes

et al. 2011

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“…For example, E. coli has three bifunctional PBPs [PBP1A, PBP1B, and PBP1C (3)], whereas Mtb has just two [PonA1 and PonA2 (8)]. Additionally, PBP2 (known as PBPA in mycobacteria) is a monofunctional PBP and is required for cell elongation in E. coli, but instead seems to function in cell septation in mycobacteria (3,9).…”

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confidence: 99%

Peptidoglycan synthesis in Mycobacterium tuberculosis is organized into networks with varying drug susceptibility

Kieser

Baranowski

Chao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Peptidoglycan (PG), a complex polymer composed of saccharide chains cross-linked by short peptides, is a critical component of the bacterial cell wall. PG synthesis has been extensively studied in model organisms but remains poorly understood in mycobacteria, a genus that includes the important human pathogen Mycobacterium tuberculosis (Mtb). The principle PG synthetic enzymes have similar and, at times, overlapping functions. To determine how these are functionally organized, we carried out whole-genome transposon mutagenesis screens in Mtb strains deleted for ponA1, ponA2, and ldtB, major PG synthetic enzymes. We identified distinct factors required to sustain bacterial growth in the absence of each of these enzymes. We find that even the homologs PonA1 and PonA2 have unique sets of genetic interactions, suggesting there are distinct PG synthesis pathways in Mtb. Either PonA1 or PonA2 is required for growth of Mtb, but both genetically interact with LdtB, which has its own distinct genetic network. We further provide evidence that each interaction network is differentially susceptible to antibiotics. Thus, Mtb uses alternative pathways to produce PG, each with its own biochemical characteristics and vulnerabilities.Mycobacterium tuberculosis | transposon sequencing | genetic interaction | peptidoglycan | cell wall

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“…Examples include the essential kinases PknA and PknB, which regulate cell shape and cell wall synthesis via phosphorylation of the cell pole-localized protein Wag31 and the septum-associated penicillin-binding protein PbpA (4)(5)(6). A kinase that has been implicated in TB pathogenesis, PknG, phosphorylates the forkhead-associated (FHA) domain-containing protein GarA, which has been shown to regulate enzymes of central carbon and nitrogen metabolism in a phosphorylation state-specific manner (7)(8)(9).…”

mentioning

confidence: 99%

Extensive phosphorylation with overlapping specificity by Mycobacterium tuberculosis serine/threonine protein kinases

Prisic

Dankwa

Schwartz

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The Mycobacterium tuberculosis genome encodes 11 serine/threonine protein kinases (STPKs) that are structurally related to eukaryotic kinases. To gain insight into the role of Ser/Thr phosphorylation in this major global pathogen, we used a phosphoproteomic approach to carry out an extensive analysis of protein phosphorylation in M. tuberculosis. We identified more than 500 phosphorylation events in 301 proteins that are involved in a broad range of functions. Bioinformatic analysis of quantitative in vitro kinase assays on peptides containing a subset of these phosphorylation sites revealed a dominant motif shared by six of the M. tuberculosis STPKs. Kinase assays on a second set of peptides incorporating targeted substitutions surrounding the phosphoacceptor validated this motif and identified additional residues preferred by individual kinases. Our data provide insight into processes regulated by STPKs in M. tuberculosis and create a resource for understanding how specific phosphorylation events modulate protein activity. The results further provide the potential to predict likely cognate STPKs for newly identified phosphoproteins.signal transduction | phosphorylation motif | phosphoproteomics A key feature of all living cells is the ability to sense environmental signals and implement adaptive changes. These inputs propagate through complex signal transduction networks whose activity is often regulated by reversible protein phosphorylation. Although Ser/Thr/Tyr protein phosphorylation-based signaling in eukaryotes has been intensively studied, the extent to which this mechanism is used in prokaryotes has only recently begun to be appreciated (1). The number of protein kinases in prokaryotes varies widely. Although many bacteria have only a few or none of these enzymes, some cyanobacteria and streptomycetes have dozens of them (2). Bacteria that do possess Ser/Thr or Tyr kinases often have complex lifestyles and depend on these kinases to regulate critical processes, such as stress adaptation, development, and virulence (2).Mycobacterium tuberculosis is an extraordinarily versatile pathogen that can exist in distinct states in the host, leading to asymptomatic latent tuberculosis (TB) infection in which bacteria are thought to be dormant, or active TB disease in which the organisms are actively replicating. To achieve these different physiologic states M. tuberculosis requires mechanisms to sense a wide range of signals from the host and to coordinately regulate multiple cellular processes. In most bacterial pathogens, the predominant phosphorylation-based signal transduction mechanism is the two-component system. The M. tuberculosis genome, however, encodes 11 Ser/Thr protein kinases (STPKs) and an equal number of two-component system sensor kinases, suggesting that these two phospho-based signaling systems are of comparable importance in this organism (3).Knowledge of the substrates of each of the M. tuberculosis STPKs is essential for understanding their function; however, only a small number of kinase-sub...

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The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division

Cited by 146 publications

References 58 publications

Characterization of CrgA, a New Partner of the Mycobacterium tuberculosis Peptidoglycan Polymerization Complexes

Characterization of CrgA, a New Partner of the Mycobacterium tuberculosis Peptidoglycan Polymerization Complexes

Peptidoglycan synthesis in Mycobacterium tuberculosis is organized into networks with varying drug susceptibility

Extensive phosphorylation with overlapping specificity by Mycobacterium tuberculosis serine/threonine protein kinases

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