A Porphyromonas gingivalis tyrosine phosphatase is a multifunctional regulator of virulence attributes.
Low Molecular Weight Tyrosine Phosphatases (LMWTP) are widespread in prokaryotes; however, understanding of the signalling cascades controlled by these enzymes is still emerging. Porphyromonas gingivalis, an opportunistic oral pathogen, expresses a LMWTP, Ltp1, that is differentially regulated in biofilm communities. Here we characterize the enzymatic activity of Ltp1 and, through the use of mutants that lack Ltp1 or expresses catalytically defective Ltp1, show that tyrosine phosphatase activity constrains both monospecies biofilm development and community development with the antecedent oral biofilm constituent Streptococcus gordonii. Exopolysaccharide production is downregulated by Ltp1 through transcriptional regulation of multiple genes involved in biosynthesis and transport. Furthermore, Ltp1 regulates transcriptional activity of luxS and thus impacts AI-2-dependent signalling in biofilm communities. In the absence of Ltp1 transcription across the hmu haemin uptake locus is reduced, and consequently uptake of haemin is impaired in the Ltp1 mutant. The gingipain proteinases Kgp and RgpA/B remain phosphorylated in the Ltp1 mutant. Phosphorylated Rgps are poorly secreted, whereas cell surface activity of phosphorylated Kgp is enhanced. By controlling the activity of several virulence-associated properties, Ltp1 may restrain the pathogenic potential of P. gingivalis and maintain a commensal interaction with the host.
Maeda
Kazuhiko
K
Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, USA.
Tribble
Gena D
GD
Tucker
Chelsea M
CM
Anaya
Cecilia
C
Shizukuishi
Satoshi
S
Lewis
Janina P
JP
Demuth
Donald R
DR
Lamont
Richard J
RJ
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016866:Bacteroidaceae Infections / Q000382:microbiology*; D018441:Biofilms / Q000254:growth & development; D013437:Carbon-Sulfur Lyases / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006418:Heme / Q000378:metabolism; D006801:Humans; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D010510:Periodontal Diseases / Q000382:microbiology*; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054773:Streptococcus gordonii / Q000235:genetics / Q000502:physiology; D013379:Substrate Specificity; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D037521:Virulence Factors; D006418:Heme; D017027:Protein Tyrosine Phosphatases; D010447:Peptide Hydrolases; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria