RESISTANCE TO HOST ANTIMICROBIAL PEPTIDES IS NECESSARY FOR SALMONELLA VIRULENCE
RESISTANCE TO HOST ANTIMICROBIAL PEPTIDES IS NECESSARY FOR SALMONELLA VIRULENCE
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DOI：
10.1073/pnas.89.24.11939
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发表时间：
1992-12-15
影响因子：
11.1
通讯作者：
HEFFRON, F
中科院分区：
文献类型：
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作者：
GROISMAN, EA;PARRALOPEZ, C;HEFFRON, F
抗菌肽的产生是各种物种（包括哺乳动物、两栖动物和昆虫）使用的宿主防御策略。成功的病原体，例如兼性细胞内细菌鼠伤寒沙门氏菌，已经进化出对这种无处不在的宿主防御类型的抵抗机制。为了鉴定对宿主肽的抗性所需的基因，我们分离了一个含有20，000个MudJ转座子插入突变体的毒力肽抗性S.鼠伤寒沙门氏菌菌株，并筛选其对抗菌肽鱼精蛋白的超敏性。18个突变体对鱼精蛋白的敏感性增加，其中12个突变体的特征进行了详细描述。11株突变株经胃内接种BALB/c小鼠后，体内毒力减弱，其中8株经腹腔接种后也表现为无毒力。这些突变体对兔防御素NP-1、蛙爪蟾抗菌肽2、猪天蚕抗菌肽P1和昆虫毒液衍生肽mastoparan和蜂毒肽的敏感性属于不同的表型类别。抗性基因定位在基因组中的八个不同位置。突变体的表征表明，一个有缺陷的脂多糖，另一个突变体在phoP中含有突变，phoP是先前显示控制沙门氏菌毒力基因表达的基因座。我们的数据表明，抵抗宿主抗菌肽杀伤作用的能力是一种毒力特性，并且在S.鼠伤寒。
The production of antibacterial peptides is a host defense strategy used by various species, including mammals, amphibians, and insects. Successful pathogens, such as the facultative intracellular bacterium Salmonella typhimurium, have evolved resistance mechanisms to this ubiquitous type of host defense. To identify the genes required for resistance to host peptides, we isolated a library of 20,000 MudJ transposon insertion mutants of a virulent peptide-resistant S. typhimurium strain and screened it for hypersensitivity to the antimicrobial peptide protamine. Eighteen mutants had heightened susceptibility to protamine and 12 of them were characterized in detail. Eleven mutants were attenuated for virulence in vivo when inoculated into BALB/c mice by the intragastric route, and 8 of them were also avirulent following intraperitoneal inoculation. The mutants fell into different phenotypic classes with respect to their susceptibility to rabbit defensin NP-1, frog magainin 2, pig cecropin P1, and the insect venom-derived peptides mastoparan and melittin. The resistance loci mapped to eight distinct locations in the genome. Characterization of the mutants showed that one had a defective lipopolysaccharide and another mutant harbored a mutation in phoP, a locus previously shown to control expression of Salmonella virulence genes. Our data indicate that the ability to resist the killing effect of host antimicrobial peptides is a virulence property and that several resistance mechanisms operate in S. typhimurium.