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Lactoferrin inhibits Porphyromonas gingivalis proteinases and has sustained biofilm inhibitory activity.
Antimicrob Agents Chemother. 2012 Mar; 56(3):1548-56.AA

Abstract

Porphyromonas gingivalis is a bacterial pathogen associated with chronic periodontitis that results in destruction of the tooth's supporting tissues. The major virulence determinants of P. gingivalis are its cell surface Arg- and Lys-specific cysteine proteinases, RgpA/B and Kgp. Lactoferrin (LF), an 80-kDa iron-binding glycoprotein found in saliva and gingival crevicular fluid, is believed to play an important role in innate immunity. In this study, bovine milk LF displayed proteinase inhibitory activity against P. gingivalis whole cells, significantly inhibiting both Arg- and Lys-specific proteolytic activities. LF inhibited the Arg-specific activity of purified RgpB, which lacks adhesin domains, and also inhibited the same activity of the RgpA/Kgp proteinase-adhesin complexes in a time-dependent manner, with a first-order inactivation rate constant (k(inact)) of 0.023 min(-1) and an inhibitor affinity constant (K(I)) of 5.02 μM. LF inhibited P. gingivalis biofilm formation by >80% at concentrations above 0.625 μM. LF was relatively resistant to hydrolysis by P. gingivalis cells but was cleaved into two major polypeptides (53 and 33 kDa) at R(284) to S(285), as determined by in-source decay mass spectrometry; however, these polypeptides remained associated with each other and retained inhibitory activity. The biofilm inhibitory activity of LF against P. gingivalis was not attributed to direct antibacterial activity, as LF displayed little growth inhibitory activity against planktonic cells. As the known RgpA/B and Kgp inhibitor N-α-p-tosyl-l-lysine chloromethylketone also inhibited P. gingivalis biofilm formation, the antibiofilm effect of LF may at least in part be attributable to its antiproteinase activity.

Authors+Show Affiliations

Oral Health CRC, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22214780

Citation

Dashper, Stuart G., et al. "Lactoferrin Inhibits Porphyromonas Gingivalis Proteinases and Has Sustained Biofilm Inhibitory Activity." Antimicrobial Agents and Chemotherapy, vol. 56, no. 3, 2012, pp. 1548-56.
Dashper SG, Pan Y, Veith PD, et al. Lactoferrin inhibits Porphyromonas gingivalis proteinases and has sustained biofilm inhibitory activity. Antimicrob Agents Chemother. 2012;56(3):1548-56.
Dashper, S. G., Pan, Y., Veith, P. D., Chen, Y. Y., Toh, E. C., Liu, S. W., Cross, K. J., & Reynolds, E. C. (2012). Lactoferrin inhibits Porphyromonas gingivalis proteinases and has sustained biofilm inhibitory activity. Antimicrobial Agents and Chemotherapy, 56(3), 1548-56. https://doi.org/10.1128/AAC.05100-11
Dashper SG, et al. Lactoferrin Inhibits Porphyromonas Gingivalis Proteinases and Has Sustained Biofilm Inhibitory Activity. Antimicrob Agents Chemother. 2012;56(3):1548-56. PubMed PMID: 22214780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lactoferrin inhibits Porphyromonas gingivalis proteinases and has sustained biofilm inhibitory activity. AU - Dashper,Stuart G, AU - Pan,Yu, AU - Veith,Paul D, AU - Chen,Yu-Yen, AU - Toh,Elena C Y, AU - Liu,Sze Wei, AU - Cross,Keith J, AU - Reynolds,Eric C, Y1 - 2012/01/03/ PY - 2012/1/5/entrez PY - 2012/1/5/pubmed PY - 2012/8/25/medline SP - 1548 EP - 56 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 56 IS - 3 N2 - Porphyromonas gingivalis is a bacterial pathogen associated with chronic periodontitis that results in destruction of the tooth's supporting tissues. The major virulence determinants of P. gingivalis are its cell surface Arg- and Lys-specific cysteine proteinases, RgpA/B and Kgp. Lactoferrin (LF), an 80-kDa iron-binding glycoprotein found in saliva and gingival crevicular fluid, is believed to play an important role in innate immunity. In this study, bovine milk LF displayed proteinase inhibitory activity against P. gingivalis whole cells, significantly inhibiting both Arg- and Lys-specific proteolytic activities. LF inhibited the Arg-specific activity of purified RgpB, which lacks adhesin domains, and also inhibited the same activity of the RgpA/Kgp proteinase-adhesin complexes in a time-dependent manner, with a first-order inactivation rate constant (k(inact)) of 0.023 min(-1) and an inhibitor affinity constant (K(I)) of 5.02 μM. LF inhibited P. gingivalis biofilm formation by >80% at concentrations above 0.625 μM. LF was relatively resistant to hydrolysis by P. gingivalis cells but was cleaved into two major polypeptides (53 and 33 kDa) at R(284) to S(285), as determined by in-source decay mass spectrometry; however, these polypeptides remained associated with each other and retained inhibitory activity. The biofilm inhibitory activity of LF against P. gingivalis was not attributed to direct antibacterial activity, as LF displayed little growth inhibitory activity against planktonic cells. As the known RgpA/B and Kgp inhibitor N-α-p-tosyl-l-lysine chloromethylketone also inhibited P. gingivalis biofilm formation, the antibiofilm effect of LF may at least in part be attributable to its antiproteinase activity. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/22214780/Lactoferrin_inhibits_Porphyromonas_gingivalis_proteinases_and_has_sustained_biofilm_inhibitory_activity_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=22214780 DB - PRIME DP - Unbound Medicine ER -