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Haemophilus ducreyi SapA Contributes to Cathelicidin Resistance and Virulence in Humans

机译:Hacreophilus ducreyi SapA有助于人类的Cathelicidin抗药性和毒力

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Haemophilus ducreyi is an extracellular pathogen of human epithelial surfaces that resists human antimicrobial peptides (APs). The organism's genome contains homologs of genes sensitive to antimicrobial peptides (sap operon) in nontypeable Haemophilus influenzae. In this study, we characterized the sap-containing loci of H. ducreyi 35000HP and demonstrated that sapA is expressed in broth cultures and H. ducreyi-infected tissue; sapA is also conserved among both class I and class II H. ducreyi strains. We constructed a nonpolar sapA mutant of H. ducreyi 35000HP, designated 35000HPsapA, and compared the percent survival of wild-type 35000HP and 35000HPsapA exposed to several human APs, including α-defensins, β-defensins, and the cathelicidin LL-37. Unlike an H. influenzae sapA mutant, strain 35000HPsapA was not more susceptible to defensins than strain 35000HP was. However, we observed a significant decrease in the survival of strain 35000HPsapA after exposure to LL-37, which was complemented by introducing sapA in trans. Thus, the Sap transporter plays a role in resistance of H. ducreyi to LL-37. We next compared mutant strain 35000HPsapA with strain 35000HP for their ability to cause disease in human volunteers. Although both strains caused papules to form at similar rates, the pustule formation rate at sites inoculated with 35000HPsapA was significantly lower than that of sites inoculated with 35000HP (33.3% versus 66.7%; P = 0.007). Together, these data establish that SapA acts as a virulence factor and as one mechanism for H. ducreyi to resist killing by antimicrobial peptides. To our knowledge, this is the first demonstration that an antimicrobial peptide resistance mechanism contributes to bacterial virulence in humans.
机译: Duemyi嗜血杆菌是人类上皮表面的一种细胞外病原体,可抵抗人类抗菌肽(APs)。该生物的基因组包含对不可分型的流感嗜血杆菌中的抗菌肽( sap 操纵子)敏感的基因的同源物。在这项研究中,我们表征了 H的包含 sap 的基因座。 ducreyi 35000HP并证明 sapA 在肉汤培养物中和 H中表达。杜克赖伊感染的组织;在I类和II类H中, sapA 也是保守的。 ducreyi 菌株。我们构建了 H的非极性 sapA 突变体。 ducreyi 35000HP,命名为35000HP sapA ,比较了暴露于几种人类AP(包括α-防御素,β)的野生型35000HP和35000HP sapA 的存活百分比-defensins和cathelicidin LL-37。与 H不同。流感病毒sapA 突变株35000HP sapA 对防御素的敏感性不比35000HP菌株高。然而,我们观察到暴露于LL-37后35000HP sapA 菌株的存活率显着降低,这是通过在 trans 中引入 sapA 来弥补的。因此,树液转运蛋白在 H的抗性中起作用。 ducreyi 至LL-37。接下来,我们比较了突变菌株35000HP sapA 和菌株35000HP在人类志愿者中引起疾病​​的能力。尽管两种菌株引起的丘疹形成率相似,但接种35000HP sapA 的部位的脓疱形成率显着低于接种35000HP的部位的脓疱形成率(33.3%对66.7%; P < / em> = 0.007)。这些数据共同证明,SapA充当毒力因子,是 H的一种机制。 ducreyi 可以抵抗抗菌肽的杀伤。据我们所知,这是抗菌肽耐药机制有助于人类细菌致病力的第一个证明。

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