Phenotypic resistance to thrombin-induced platelet microbicidal protein in vitro is correlated with enhanced virulence in experimental endocarditis due to Staphylococcus aureus
Phenotypic resistance to thrombin-induced platelet microbicidal protein in vitro is correlated with enhanced virulence in experimental endocarditis due to Staphylococcus aureus
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DOI：
10.1128/iai.65.8.3293-3299.1997
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发表时间：
1997-08-01
影响因子：
3.1
通讯作者：
Bayer, AS
中科院分区：
文献类型：
--
作者：
Dhawan, VK;Yeaman, MR;Bayer, AS
凝血酶诱导的血小板杀微生物蛋白（tPMP）是由兔血小板在凝血酶刺激后分泌的，它在体外杀死常见的血管内病原体，包括金黄色葡萄球菌，因此，在体外表现出tPMP抗性的病原体在血管内损伤部位具有潜在的生存优势。通过转座子（Tn551）诱变tPMP易感（tPMP(s)）亲本菌株（ISP479），获得稳定的tPMP抗性（tPMP(r)）菌株ISP479R。ISP479和ISP479R在以下表型上是相同的：生物分型、抗菌素谱、血小板粘附和聚集、生长动力学、细胞壁相关蛋白A表达和纤维蛋白原结合，ISP479和ISP479R菌株在限制性内切酶酶切后的染色体DNA基因型比较显示出难以区分的脉冲场凝胶电泳模式。菌株ISP479R表现出的基因型与tpmp抗性表型相关，因为它可以转导到最初的tpmp敏感亲本菌株。ISP479， Southern杂交证实了在ISP479R和ISP479的tPMP(r)转导因子的同一染色体限制性位点存在Tn551的单拷贝。体外tPMP易感性表型与诱导实验性心内膜炎（一种典型的血管内感染）的能力的相关性进行了评估，尽管心内膜炎诱导率相当，与感染菌株ISP479的动物相比，感染菌株ISP479R的动物在攻毒后7天内获得了显著更高的植被细菌密度。这些数据表明，tPMP(r)微生物菌株在实验性葡萄球菌心内膜炎中具有选择性优势。此外，tPMP耐药性对心内膜炎发病机制的主要影响似乎涉及瓣膜后粘附事件，最可能是通过促进植被内的细菌增殖。
Thrombin-induced platelet microbicidal protein (tPMP) is secreted by rabbit platelets following thrombin stimulation, and it kills common endovascular pathogens in vitro, including Staphylococcus aureus, Therefore, pathogens which exhibit tPMP resistance in vitro possess a potential survival advantage in vivo at sites of endovascular damage, We generated an isogenic S. aureus strain pair, differing in tPMP susceptibility, by transposon (Tn551) mutagenesis of a tPMP-susceptible (tPMP(s)) parental strain (ISP479) to derive a stably tPMP-resistant (tPMP(r)) strain, ISP479R. ISP479 and ISP479R were equivalent in vitro in the following phenotypes: biotyping, antiobiograms, platelet adherence and aggregation, growth kinetics, cell wall-associated protein A expression, and fibrinogen binding, Genotypic comparisons of chromosomal DNA of strains ISP479 and ISP479R following restriction endonuclease digestion revealed indistinguishable pulsed-field gel electrophoretic patterns, The genotype exhibited by strain ISP479R was linked to the tPMP-resistant phenotype, as it was transducible into the initially tPMP-susceptible parental strain, ISP479, Southern hybridization verified the presence of a single copy of Tn551 in the same chromosomal restriction site of both ISP479R and tPMP(r) transductants of ISP479, The correlation of in vitro tPMP susceptibility phenotypes with the ability to induce experimental endocarditis (a prototypical endovascular infection) was evaluated, Despite equivalent rates of endocarditis induction, animals infected with strain ISP479R achieved significantly higher vegetation bacterial densities over a 7-day post-challenge period than did animals infected with strain ISP479. These data suggest that tPMP(r) microbial strains have a selective advantage in experimental staphylococcal endocarditis, Furthermore, the major impact of tPMP resistance upon endocarditis pathogenesis appears to involve a postvalvular adherence event(s), most probably by facilitating bacterial proliferation within vegetations.