Selective depletion of Campylobacter jejuni via T6SS dependent functionality: an approach for improving chickens gut health.

IF 4.3 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Subhadeep Gupta, Prakash Biswas, Bishnu Das, Samiran Mondal, Parna Gupta, Dipjyoti Das, Amirul Islam Mallick
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Abstract

The targeted depletion of potential gut pathogens is often challenging because of their intrinsic ability to thrive in harsh gut environments. Earlier, we showed that Campylobacter jejuni (C. jejuni) exclusively uses the Type-VI Secretion System (T6SS) to target its prey such as Escherichia coli (E. coli), and phenotypic differences between T6SS-negative and T6SS-positive C. jejuni isolates toward bile salt sensitivity. However, it remains unclear how the target-driven T6SS functionality prevails in a polymicrobial gut environment. Here, we investigated the fate of microbial competition in an altered gut environment via bacterial T6SS using a T6SS-negative and -positive C. jejuni or its isogenic mutant of the hemolysin-coregulated protein (hcp). We showed that in the presence of bile salt and prey bacteria (E. coli), T6SS-positive C. jejuni experiences enhanced intracellular stress leading to cell death. Intracellular tracking of fluorophore-conjugated bile salts confirmed that T6SS-mediated bile salt influx into C. jejuni can enhance intracellular oxidative stress, affecting C. jejuni viability. We further investigated whether the T6SS activity in the presence of prey (E. coli) perturbs the in vivo colonization of C. jejuni. Using chickens as primary hosts of C. jejuni and non-pathogenic E. coli as prey, we showed a marked reduction of C. jejuni load in chickens cecum when bile salt solution was administered orally. Analysis of local antibody responses and pro-inflammatory gene expression showed a reduced risk of tissue damage, indicating that T6SS activity in the complex gut environment can be exploited as a possible measure to clear the persistent colonization of C. jejuni in chickens.

通过 T6SS 依赖性功能选择性去除空肠弯曲杆菌:改善鸡肠道健康的一种方法。
由于潜在的肠道病原体具有在恶劣的肠道环境中茁壮成长的内在能力,因此有针对性地消灭它们往往具有挑战性。早些时候,我们发现空肠弯曲杆菌(C. jejuni)专门使用 VI 型分泌系统(T6SS)来靶向其猎物,如大肠埃希菌(E. coli),并发现 T6SS 阴性和 T6SS 阳性空肠弯曲杆菌分离物对胆盐敏感的表型差异。然而,目标驱动的 T6SS 功能如何在多微生物肠道环境中占主导地位仍不清楚。在这里,我们使用 T6SS 阴性和阳性空肠病菌或其溶血素调控蛋白(hcp)的同源突变体,通过细菌 T6SS 研究了在改变的肠道环境中微生物竞争的命运。我们的研究表明,在胆盐和猎物细菌(大肠杆菌)存在的情况下,T6SS 阳性的空肠杆菌会经历更强的细胞内应力,导致细胞死亡。对荧光团共轭胆盐的细胞内追踪证实,T6SS 介导的胆盐流入空肠杆菌可增强细胞内氧化应激,从而影响空肠杆菌的存活率。我们进一步研究了在有猎物(大肠杆菌)存在的情况下,T6SS 的活性是否会干扰空肠大肠杆菌的体内定植。以鸡作为空肠大肠杆菌的主要宿主,以非致病性大肠杆菌作为猎物,我们发现当口服胆盐溶液时,空肠大肠杆菌在鸡盲肠中的载量明显减少。对局部抗体反应和促炎基因表达的分析表明,组织损伤的风险降低了,这表明可以利用复杂肠道环境中的 T6SS 活性作为清除空肠大肠杆菌在鸡体内持续定植的一种可能措施。
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来源期刊
Gut Pathogens
Gut Pathogens GASTROENTEROLOGY & HEPATOLOGY-MICROBIOLOGY
CiteScore
7.70
自引率
2.40%
发文量
43
期刊介绍: Gut Pathogens is a fast publishing, inclusive and prominent international journal which recognizes the need for a publishing platform uniquely tailored to reflect the full breadth of research in the biology and medicine of pathogens, commensals and functional microbiota of the gut. The journal publishes basic, clinical and cutting-edge research on all aspects of the above mentioned organisms including probiotic bacteria and yeasts and their products. The scope also covers the related ecology, molecular genetics, physiology and epidemiology of these microbes. The journal actively invites timely reports on the novel aspects of genomics, metagenomics, microbiota profiling and systems biology. Gut Pathogens will also consider, at the discretion of the editors, descriptive studies identifying a new genome sequence of a gut microbe or a series of related microbes (such as those obtained from new hosts, niches, settings, outbreaks and epidemics) and those obtained from single or multiple hosts at one or different time points (chronological evolution).
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