OmpA-Like Proteins of Porphyromonas gingivalis Mediate Resistance to the Antimicrobial Peptide LL-37

OmpA-Like Proteins of Porphyromonas gingivalis Mediate Resistance to the Antimicrobial Peptide LL-37
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DOI:
10.1155/2018/2068435
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发表时间:
2018-12
影响因子:
2.6
通讯作者:
T. Horie;M. Inomata;T. Into
T. Horie;M. Inomata;T. Into
中科院分区:
--
文献类型:
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作者:
T. Horie;M. Inomata;T. Into

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牙龈下细菌不断暴露在从血清中提取的牙周沟液中,其中含有各种杀菌剂。牙周病细菌牙龈卟啉单胞菌已被证明具有多种抵抗杀菌剂的能力,因此它能够在龈下环境中繁殖。我们以前已经证明,牙龈假单胞菌的主要表面糖蛋白Pgm6和Pgm7,也称为外膜蛋白A样蛋白(OmpALPs)-介导对人血清杀菌活性的抗性,但它们的确切作用尚不清楚。在这项研究中,我们研究了野生型和Pgm6/Pgm7缺陷的Pgm6/Pgm7菌株对口腔中主要抗菌肽、人β防御素(HBDS)1-3和人放线菌素LL-37的敏感性。HBDS对两种细菌均表现出相当弱的杀菌活性。LL-37对野生型菌株也表现出较弱的活性,但对Pgm6/Pgm7缺陷菌株表现出显著的活性。在Pgm6/Pgm7缺陷菌株中,IL-37显著聚集在细菌细胞表面,可能导致外膜的破坏。此外,在LL-37的存在下,hBDS对Pgm6/Pgm7缺陷菌株的杀菌活性被发现协同促进。我们的结果表明,OmpALP特异性地保护牙龈假单胞菌免受LL-37的杀菌活性;因此,牙龈假单胞菌可能熟练地在产生LL-37的牙龈下环境中生存。
Subgingival bacteria are continually exposed to gingival crevicular fluids that are derived from serum, which contain various bactericidal agents. The periodontopathic bacterium Porphyromonas gingivalis has been demonstrated to possess a variety of abilities to resist bactericidal agents, due to which it is able to propagate in the subgingival environment. We previously demonstrated that the major surface glycoproteins of P. gingivalis—Pgm6 and Pgm7, also called outer membrane protein A-like proteins (OmpALPs)—mediate resistance to the bactericidal activity of human serum, but their precise role remains unknown. In this study, we investigated the sensitivity of the wild-type and Pgm6/Pgm7-deficient P. gingivalis strains toward major antimicrobial peptides in the oral cavity, human β-defensins (hBDs) 1-3, and human cathelicidin LL-37. hBDs showed a considerably weak bactericidal activity against both bacterial strains. LL-37 also showed a weak activity against the wild-type strain; however, it showed a significant activity against the Pgm6/Pgm7-deficient strain. In the Pgm6/Pgm7-deficient strain, LL-37 remarkably accumulated on the bacterial cell surface, which may result in the destruction of the outer membrane. Additionally, the bactericidal activity of hBDs against the Pgm6/Pgm7-deficient strain was found to be synergistically promoted in the presence of LL-37. Our results suggest that OmpALPs specifically protect P. gingivalis from the bactericidal activity of LL-37; thus, P. gingivalis may adeptly survive in LL-37-producing subgingival environments.