Vibrio cholerae Alkalizes Its Environment via Citrate Metabolism to Inhibit Enteric Growth In Vitro.

Vibrio cholerae Alkalizes Its Environment via Citrate Metabolism to Inhibit Enteric Growth In Vitro.
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DOI:
10.1128/spectrum.04917-22
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发表时间:
2023-03-14
影响因子:
3.7
通讯作者:
--
中科院分区:
生物学1区
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--
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霍乱弧菌是一种革兰氏阴性病原体,在海洋环境和人类感染期间与其他细菌不断竞争。霍乱弧菌的一个竞争优势是代谢多种碳源的能力,如几丁质和柠檬酸盐。我们观察到,当一些霍乱弧菌菌株在柠檬酸盐培养基上生长时,培养基的化学成分变成了对革兰氏阴性细菌(如大肠杆菌和福氏志贺氏菌)不利的碱性环境。我们发现,尽管排除竞争细菌的能力并不取决于外源柠檬酸盐,但霍乱弧菌C6706柠檬酸盐代谢突变体ΔoadA-1、ΔcitE和ΔcitF不能抑制弗氏沙门氏菌或大肠杆菌的生长。最后,我们证明,虽然霍乱弧菌c6706介导的培养基pH升高是肠排斥表型的必要条件,但次级代谢物,如柠檬酸盐代谢产生的碳酸氢盐(在pH升高时质子化为碳酸盐),增强了抑制大肠杆菌生长的能力。这些数据为霍乱弧菌如何战胜其他革兰氏阴性菌提供了一个新的例子。霍乱弧菌必须与其他细菌竞争才能引起疾病。在这里,我们表明霍乱弧菌创造了一个碱性环境,能够抑制其他肠道细菌的生长。我们证明霍乱弧菌环境碱化与细菌代谢柠檬酸盐的能力有关。这种行为可能有助于霍乱弧菌在人类肠道中定植的能力。
Vibrio cholerae is a Gram-negative pathogen, living in constant competition with other bacteria in marine environments and during human infection. One competitive advantage of V. cholerae is the ability to metabolize diverse carbon sources, such as chitin and citrate. We observed that when some V. cholerae strains were grown on a medium with citrate, the medium’s chemical composition turned into a hostile alkaline environment for Gram-negative bacteria, such as Escherichia coli and Shigella flexneri. We found that although the ability to exclude competing bacteria was not contingent on exogenous citrate, V. cholerae C6706 citrate metabolism mutants ΔoadA-1, ΔcitE, and ΔcitF were not able to inhibit S. flexneri or E. coli growth. Lastly, we demonstrated that while the V. cholerae C6706-mediated increased medium pH was necessary for the enteric exclusion phenotype, secondary metabolites, such as bicarbonate (protonated to carbonate in the raised pH) from the metabolism of citrate, enhanced the ability to inhibit the growth of E. coli. These data provide a novel example of how V. cholerae outcompetes other Gram-negative bacteria. IMPORTANCE Vibrio cholerae must compete with other bacteria in order to cause disease. Here, we show that V. cholerae creates an alkaline environment, which is able to inhibit the growth of other enteric bacteria. We demonstrate that V. cholerae environmental alkalization is linked to the capacity of the bacteria to metabolize citrate. This behavior could potentially contribute to V. cholerae’s ability to colonize the human intestine.
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