Resistance of Porphyromonas gingivalis ATCC 33277 to direct killing by antimicrobial peptides is protease independent
Resistance of Porphyromonas gingivalis ATCC 33277 to direct killing by antimicrobial peptides is protease independent
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DOI：
10.1128/aac.01271-07
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发表时间：
2008-02-01
影响因子：
4.9
通讯作者：
Steinberg, Doron
中科院分区：
文献类型：
--
作者：
Bachrach, Gilad;Altman, Hamutal;Steinberg, Doron
抗菌肽是一种短的、带正电荷的两亲性多肽，具有广谱的抗菌活性，在宿主的先天免疫中具有重要作用。抗微生物肽的缺乏或功能障碍与包括牙周炎在内的感染性疾病相关。牙龈卟啉单胞菌是一种革兰氏阴性厌氧菌，是牙周病的主要致病菌，对人源和非人源的抗菌肽具有耐药性，这一特征可能有助于其毒力。牙龈卟啉单胞菌表达强大的蛋白水解活性，水解抗微生物肽。在这项研究中，牙龈卟啉单胞菌灭活三种抗菌肽，而D-对映体对降解具有抗性。牙龈卟啉单胞菌对蛋白酶抗性D-对映体肽具有抗性，重要的是，蛋白酶缺陷型牙龈卟啉单胞菌突变体也对抗菌肽具有抗性。最后，荧光标记的抗菌肽与蛋白酶缺陷型牙龈卟啉单胞菌的结合比与敏感性大肠杆菌的结合弱得多。我们的结果表明，牙龈卟啉单胞菌ATCC 33277对抗菌肽直接杀灭的抗性是蛋白酶无关的，并且（至少部分地）是由抗菌肽对牙龈卟啉单胞菌的低亲和力引起的。
Antimicrobial peptides are short, positively charged, amphipathic peptides that possess a wide spectrum of antimicrobial activity and have an important role in the host's innate immunity. Lack of, or dysfunctions in, antimicrobial peptides have been correlated with infectious diseases, including periodontitis. Porphyromonas gingivalis, a gram-negative anaerobe and a major pathogen associated with periodontal diseases, is resistant to antimicrobial peptides of human and nonhuman origin, a feature that likely contributes to its virulence. Expressing a robust proteolytic activity, P. gingivalis hydrolyzes antimicrobial peptides. In this study, P. gingivalis inactivated three antimicrobial peptides, while a D-enantiomer was resistant to degradation. P. gingivalis was resistant to the protease-resistant D-enantiomer peptide, and importantly, a protease-deficient P. gingivalis mutant was also resistant to the antimicrobial peptide. Finally, the binding of a fluorescently labeled antimicrobial peptide to protease-deficient P. gingivalis was much weaker than the binding of susceptible Escherichia coli. Our results suggest that the resistance of P. gingivalis ATCC 33277 to direct killing by antimicrobial peptides is protease independent and results (at least partially) from the low affinity of antimicrobial peptides to P. gingivalis.