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Identification and characterization of differentially expressed genes in Caenorhabditis elegans in response to pathogenic and nonpathogenic Stenotrophomonas maltophilia.
BMC Microbiology ( IF 4.0 ) Pub Date : 2020-06-19 , DOI: 10.1186/s12866-020-01771-1
Leah J Radeke 1 , Michael A Herman 1
Affiliation  

Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes infection in immunocompromised patients. S. maltophilia isolates are genetically diverse, contain diverse virulence factors, and are variably pathogenic within several host species. Members of the Stenotrophomonas genus are part of the native microbiome of C. elegans, being found in greater relative abundance within the worm than its environment, suggesting that these bacteria accumulate within C. elegans. Thus, study of the C. elegans-Stenotrophomonas interaction is of both medical and ecological significance. To identify host defense mechanisms, we analyzed the C. elegans transcriptomic response to S. maltophilia strains of varying pathogenicity: K279a, an avirulent clinical isolate, JCMS, a virulent strain isolated in association with soil nematodes near Manhattan, KS, and JV3, an even more virulent environmental isolate. Overall, we found 145 genes that are commonly differentially expressed in response to pathogenic S. maltophilia strains, 89% of which are upregulated, with many even further upregulated in response to JV3 as compared to JCMS. There are many more JV3-specific differentially expressed genes (225, 11% upregulated) than JCMS-specific differentially expressed genes (14, 86% upregulated), suggesting JV3 has unique pathogenic mechanisms that could explain its increased virulence. We used connectivity within a gene network model to choose pathogen-specific and strain-specific differentially expressed candidate genes for functional analysis. Mutations in 13 of 22 candidate genes caused significant differences in C. elegans survival in response to at least one S. maltophilia strain, although not always the strain that induced differential expression, suggesting a dynamic response to varying levels of pathogenicity. Variation in observed pathogenicity and differences in host transcriptional responses to S. maltophilia strains reveal that strain-specific mechanisms play important roles in S. maltophilia pathogenesis. Furthermore, utilizing bacteria closely related to strains found in C. elegans natural environment provides a more realistic interaction for understanding host-pathogen response.

中文翻译:


秀丽隐杆线虫响应致病性和非致病性嗜麦芽窄食单胞菌差异表达基因的鉴定和表征。



嗜麦芽寡养单胞菌是一种新出现的医院病原体,可导致免疫功能低下患者感染。嗜麦芽糖链球菌分离株具有遗传多样性,含有多种毒力因子,并且在多个宿主物种内具有不同的致病性。寡养单胞菌属的成员是秀丽隐杆线虫天然微生物组的一部分,在线虫体内的相对丰度高于其环境,表明这些细菌在秀丽隐杆线虫内积累。因此,研究线虫与寡养单胞菌相互作用具有医学和生态学意义。为了确定宿主防御机制,我们分析了秀丽隐杆线虫对不同致病性的嗜麦芽糖链球菌菌株的转录组反应:K279a,一种无毒力的临床分离株,JCMS,一种与堪萨斯州曼哈顿附近的土壤线虫相关的有毒菌株,以及JV3,一种甚至毒性更强的环境隔离物。总体而言,我们发现了 145 个基因在对致病性嗜麦芽糖链球菌菌株的反应中通常存在差异表达,其中 89% 上调,与 JCMS 相比,许多基因在对 JV3 的反应中甚至进一步上调。 JV3 特异性差异表达基因(225 个,上调 11%)比 JCMS 特异性差异表达基因(14 个,上调 86%)多,表明 JV3 具有独特的致病机制,可以解释其毒力增加。我们使用基因网络模型内的连接性来选择病原体特异性和菌株特异性差异表达候选基因进行功能分析。 22 个候选基因中有 13 个的突变导致线虫对至少一种线虫的存活率存在显着差异。 嗜麦芽菌株,尽管并不总是诱导差异表达的菌株,这表明对不同致病性水平的动态反应。观察到的致病性的变化和宿主对嗜麦芽糖链球菌菌株转录反应的差异表明,菌株特异性机制在嗜麦芽糖链球菌发病机制中发挥着重要作用。此外,利用与秀丽隐杆线虫自然环境中发现的菌株密切相关的细菌为理解宿主-病原体反应提供了更真实的相互作用。
更新日期:2020-06-19
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