Roles of Arg- and Lys-gingipains in coaggregation of Porphyromonas gingivalis: identification of its responsible molecules in translation products of rgpA, kgp, and hagA genes.
Arg- (Rgp) and Lys-gingipains (Kgp) are two individual cysteine proteinases produced by Porphyromonas gingivalis , an oral anaerobic bacterium, and are implicated as major virulence factors in a wide range of pathologies of adult periodontitis. Coaggregation of this bacterium with other oral bacteria is an initial and critical step in infectious processes, yet the factors and mechanisms responsible for this process remain elusive. Here we show that the initial translation products of the rgpA , kgp and hemagglutinin hagA genes are responsible for coaggregation of P. gingivalis and that the proteolytic activity of Rgp and Kgp is indispensable in this process. The rgpA rgpB kgp- and rgpA kgp hagA -deficient triple mutants exhibited no coaggregation activity with Actinomyces viscosus , whereas the kgp -null and rgpA rgpB -deficient double mutants significantly retained this activity. Consistently, the combined action of Rgp- and Kgp-specific inhibitors strongly inhibited the coaggregation activity of the bacterium, although single use of Rgp- or Kgp-specific inhibitor significantly retained this activity. We also demonstrate that the 47- and 43-kDa proteins produced from the translation products of the rgpA , kgp , and hagA genes by proteolytic activity of both Rgp and Kgp are responsible for the coaggregation of P. gingivalis.
Abe
Naoko
N
Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Baba
Atsuyo
A
Takii
Ryosuke
R
Nakayama
Koji
K
Kamaguchi
Arihide
A
Shibata
Yasuko
Y
Abiko
Yoshimitsu
Y
Okamoto
Kuniaki
K
Kadowaki
Tomoko
T
Yamamoto
Kenji
K
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins / Q000235:genetics*; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology*; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology*; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000502:physiology*; D014176:Protein Biosynthesis
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D003546:Cysteine Endopeptidases