A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria.

A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria.
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DOI:
10.1128/mbio.00656-21
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发表时间:
2021-08-31
期刊:
影响因子:
6.4
通讯作者:
Goodman AL
Goodman AL
中科院分区:
生物学1区
文献类型:
--
作者:
Bao Y;Verdegaal AA;Anderson BW;Barry NA;He J;Gao X;Goodman AL

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人类肠道微生物表现出一系列与宿主以及其他微生物的合作和拮抗相互作用。脆弱拟杆菌毒素(Bacteroides fragilis toxin,BFT)是拟杆菌属的主要宿主靶向毒力因子,由肠毒素生成菌B产生。fragilis菌株。BFT由保守的细菌半胱氨酸蛋白酶fragipain(Fpn)加工,其也在B中编码。缺乏BFT的脆弱菌株。在这份报告中,我们确定了分泌的抗菌蛋白(fragipain-activated bacteriocin 1 [Fab 1])和它的同源免疫蛋白(耐fragipain-活化的细菌素1 [RFab 1])在肠道致病性和非致病性菌株的B。脆弱的。虽然BFT和Fab 1没有序列同一性,但Fpn也激活Fab 1原毒素,导致其分泌和抗菌活性。这些发现突出了肠道细菌中宿主和细菌靶向毒素之间的共性,并表明抗菌拮抗作用可能促进激活宿主靶向毒力因子的途径的保护。
Human gut microbes exhibit a spectrum of cooperative and antagonistic interactions with their host and also with other microbes. The major Bacteroides host-targeting virulence factor, Bacteroides fragilis toxin (BFT), is produced as an inactive protoxin by enterotoxigenic B. fragilis strains. BFT is processed by the conserved bacterial cysteine protease fragipain (Fpn), which is also encoded in B. fragilis strains that lack BFT. In this report, we identify a secreted antibacterial protein (fragipain-activated bacteriocin 1 [Fab1]) and its cognate immunity protein (resistance to fragipain-activated bacteriocin 1 [RFab1]) in enterotoxigenic and nontoxigenic strains of B. fragilis. Although BFT and Fab1 share no sequence identity, Fpn also activates the Fab1 protoxin, resulting in its secretion and antibacterial activity. These findings highlight commonalities between host- and bacterium-targeting toxins in intestinal bacteria and suggest that antibacterial antagonism may promote the conservation of pathways that activate host-targeting virulence factors.