Inflammation fuels colicin Ib-dependent competition of Salmonella serovar Typhimurium and E. coli in enterobacterial blooms.
Inflammation fuels colicin Ib-dependent competition of Salmonella serovar Typhimurium and E. coli in enterobacterial blooms.
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DOI：
10.1371/journal.ppat.1003844
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发表时间：
2014-01
期刊：
影响因子：
6.7
通讯作者：
Stecher B
中科院分区：
文献类型：
--
作者：
Nedialkova LP;Denzler R;Koeppel MB;Diehl M;Ring D;Wille T;Gerlach RG;Stecher B
宿主的免疫系统在调节肠道病原体和肠道微生物群的生长方面发挥着关键作用。特别是，炎症性肠病和病原体感染会引起常驻共生微生物群的变化，从而导致肠杆菌科细菌过度生长（“炎症引起的细菌繁殖”）。在这里，我们研究了人类致病性肠沙门氏菌鼠伤寒血清型 SL1344 (S. Tm) 菌株和共生大肠杆菌在引起炎症的水华中的竞争。 S.Tm 产生大肠菌素 Ib (ColIb)，这是一种窄谱蛋白毒素，对相关肠杆菌科细菌具有活性。在发炎肠道中，ColIb 的产生赋予了 S.Tm 相对于敏感大肠杆菌菌株的竞争优势。相比之下，缺乏触发肠道炎症的无毒力 S.Tm 突变株并没有从 ColIb 中获益。 ColIb (cib) 的表达受铁限制和 SOS 反应的调节。 CirA 是大肠菌素敏感的大肠杆菌上 ColIb 的同源外膜受体，在铁限制时被诱导。我们证明，炎症诱导的藻华生长有利于 S.Tm ColIb 和受体 CirA 的表达，从而促进肠道中 S.Tm 和共生大肠杆菌的 ColIb 依赖性竞争。总之，这项研究揭示了炎症引起的水华作为一种有利于肠杆菌科致病性和共生代表之间的 ColIb 依赖性竞争的环境，其作用迄今为止尚未得到重视。大肠杆菌素是细菌蛋白毒素，在体外对敏感菌株表现出有效的活性。生态模型表明，大肠菌素在调节肠道细菌种群动态方面发挥着重要作用。然而，之前的研究无法通过各自的体内实验轻易证实这些预测。在动物模型中，与敏感的竞争者相比，产生大肠菌素的菌株仅表现出较小甚至没有的健身益处。在这里，我们提出肠道环境在为大肠菌素 Ib (ColIb) 细菌竞争创造条件方面发挥着至关重要的作用。肠道炎症有利于肠杆菌科细菌的过度生长（“炎症引起的肠杆菌大量繁殖”）。我们发现，致病性鼠伤寒沙门氏菌 (S.Tm) 菌株在受炎症影响的花朵中生长时，可以与共生大肠杆菌竞争，从而受益于 ColIb 的产生。在没有肠道炎症的情况下，ColIb 的生产并没有赋予 S. Tm 竞争优势。与未发炎的肠道相比，在发炎的肠道中，S.Tm 中产生 ColIb 的基因及其在大肠杆菌中相应的 ColIb 表面受体 CirA 被显着诱导。因此，炎症引起的水华中的环境条件通过同时触发 ColIb 的产生和敏感性，有利于肠杆菌科细菌的大肠菌素依赖性竞争。我们的研究结果揭示了大肠菌素在炎症引起的藻华中作为重要的细菌适应性因子的作用。
The host's immune system plays a key role in modulating growth of pathogens and the intestinal microbiota in the gut. In particular, inflammatory bowel disorders and pathogen infections induce shifts of the resident commensal microbiota which can result in overgrowth of Enterobacteriaceae (“inflammation-inflicted blooms”). Here, we investigated competition of the human pathogenic Salmonella enterica serovar Typhimurium strain SL1344 (S. Tm) and commensal E. coli in inflammation-inflicted blooms. S. Tm produces colicin Ib (ColIb), which is a narrow-spectrum protein toxin active against related Enterobacteriaceae. Production of ColIb conferred a competitive advantage to S. Tm over sensitive E. coli strains in the inflamed gut. In contrast, an avirulent S. Tm mutant strain defective in triggering gut inflammation did not benefit from ColIb. Expression of ColIb (cib) is regulated by iron limitation and the SOS response. CirA, the cognate outer membrane receptor of ColIb on colicin-sensitive E. coli, is induced upon iron limitation. We demonstrate that growth in inflammation-induced blooms favours expression of both S. Tm ColIb and the receptor CirA, thereby fuelling ColIb dependent competition of S. Tm and commensal E. coli in the gut. In conclusion, this study uncovers a so-far unappreciated role of inflammation-inflicted blooms as an environment favouring ColIb-dependent competition of pathogenic and commensal representatives of the Enterobacteriaceae family. Colicins are bacterial protein toxins which show potent activity against sensitive strains in vitro. Ecological models suggest that colicins play a major role in modulating dynamics of bacterial populations in the gut. However, previous studies could not readily confirm these predictions by respective in vivo experiments. In animal models, colicin-producing strains only show a minor or even absent fitness benefit over sensitive competitors. Here, we propose that the gut environment plays a crucial role in generating conditions for bacterial competition by colicin Ib (ColIb). Gut inflammation favours overgrowth of Enterobacteriaceae (“inflammation-inflicted Enterobacterial blooms”). We show that a pathogenic Salmonella Typhimurium (S. Tm) strain benefits from ColIb production in competition against commensal E. coli upon growth in inflammation-inflicted blooms. In the absence of gut inflammation, ColIb production did not confer a competitive advantage to S. Tm. In the inflamed gut, the genes for ColIb production in S. Tm and its corresponding ColIb-surface receptor CirA in E. coli were markedly induced, as compared to the non-inflamed gut. Therefore, environmental conditions in inflammation-inflicted blooms favour colicin-dependent competition of Enterobacteriaceae by triggering ColIb production and susceptibility at the same time. Our findings reveal a role of colicins as important bacterial fitness factors in inflammation-induced blooms.
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影响因子：
3.2
作者：
GOERLICH, O;QUILLARDET, P;HOFNUNG, M
通讯作者：
HOFNUNG, M
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
DOI：
10.1073/pnas.78.10.6324
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CHAO, L;LEVIN, BR
通讯作者：
LEVIN, BR
影响因子：
3.2
作者：
GRIGGS, DW;THARP, BB;KONISKY, J
通讯作者：
KONISKY, J
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL