Mechanisms of decreased susceptibility to beta-defensins by Treponema denticola.
Mechanisms of decreased susceptibility to beta-defensins by Treponema denticola.
复制标题
齿垢密螺旋体降低对 β-防御素敏感性的机制。
DOI：
10.1128/iai.01718-06
复制
发表时间：
2007
影响因子：
3.1
通讯作者：
Lukehart,SheilaA
中科院分区：
文献类型：
--
作者：
Brissette,CatherineA;Lukehart,SheilaA
Treponema denticola, a periodontal pathogen, is relatively resistant to human beta-defensins, which are small cationic antimicrobial peptides produced by a number of cells, including the gingival epithelium. Using two independent methods, we previously demonstrated thatT. denticolaproteases are not responsible for decreased vulnerability to defensins. In this study, we confirmed that the major outer membrane protease, dentilisin, is not responsible forT. denticolainsensitivity to defensins and examined several other possible mechanisms, including reduced binding to the bacterial surface and efflux pump activity. It has been suggested that some bacteria mask their surfaces with serum proteins.T. denticolagrown in a serum-free medium did not exhibit increased susceptibility to human beta-defensin 2 and 3 (hβD-2 and hβD-3, respectively), suggesting that cloaking of the outer surface with host proteins is not involved in defensin resistance. Nonetheless, we demonstrated thatT. denticolabinds significantly less hβD-2 and -3 than susceptible organisms bind, suggesting that the unusual outer membrane composition ofT. denticolamay discourage cationic peptide binding. Efflux pumps have been shown to mediate resistance to antibiotics and cationic peptides in other bacteria, and their role inT. denticola's relative resistance to β-defensins was investigated. Three inhibitors of bacterial ATP-binding cassette (ABC) efflux pumps had no effect onT. denticola's susceptibility to hβD-2 or -3. In contrast, a proton motive force inhibitor, carbonyl cyanide 3-chlorophenylhydrazone, increased the susceptibility ofT. denticolato killing by hβD-3, demonstrating a potential role for efflux pumps (other than ABC pumps) in resistance to this peptide. Our data suggest that the combination of decreased defensin binding and efflux of any peptide which enters the cytoplasm may explainT. denticola's relative resistance to human beta-defensins.
