A novel bacteriocin produced by Bifidobacterium longum subsp. infantis has dual antimicrobial and immunomodulatory activity

A novel bacteriocin produced by Bifidobacterium longum subsp. infantis has dual antimicrobial and immunomodulatory activity
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一种由长双歧杆菌亚种产生的新型细菌素。

DOI:
10.1101/2022.01.27.477972
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发表时间:
2022
期刊:
--
影响因子:
--
通讯作者:
Javvadi S
Javvadi S
中科院分区:
--
文献类型:
--
作者:
Javvadi S

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细菌素是由细菌合成的具有窄谱或广谱活性的核糖体抗菌肽。许多基因组挖掘研究表明,细菌素基因簇广泛存在于某些肠道微生物区系成员中。在生命早期,双歧杆菌在阴道分娩和母乳喂养的婴儿中占主导地位,其水平较高与健康改善有关。然而,在许多情况下,这些有益效果背后的机制尚不清楚,尽管有限的一些研究表明,双歧杆菌产生细菌素可能是防止病原体过度生长的关键机制。在这里,我们使用BAGEL4和抗SMASH来鉴定从两个临床研究中分离的33株双歧杆菌全基因组序列中可能的细菌素序列。我们从婴儿长双歧杆菌LH664中鉴定出一种新的非抗生素细菌素,与乳球菌乳酸亚种中的乳球菌素972有40%的序列同源性。化学合成了可能的细菌素(双歧球菌素664),并对其抗菌和免疫调节活性进行了研究。我们确定它对产气荚膜梭菌具有离散的活性,并且它似乎具有新的免疫刺激活性,促进巨噬细胞吞噬和特异性细胞因子的释放。这些数据突出了早期生命基因双歧杆菌中菌株特有的有益性质,并为开发新型和高度特异的双重作用抗菌剂和可能的益生菌菌株提供了途径,这些抗菌剂对临床上重要的细菌病原体具有活性。数据摘要样本LH_9至LH_666先前已测序,并以登录号ERS2658025-ERS2658043存放在ENA。LH986至LH1052是新的序列,并以登录号SAMN24838598-SAMN24838611保存在NCBI上。此外,从NCBI基因组数据库中在线检索先前组装的公开可用序列(n=7)。有关更多详细信息,请参阅补充表S1。
Bacteriocins are ribosomally-synthesized antimicrobial peptides produced by bacteria with either narrow or broad spectrum activity. Many genome mining studies have indicated that bacteriocin gene clusters are widespread within certain gut microbiota members. In early life,Bifidobacteriumcomprise the dominant microbiota genus in vaginally delivered and breast-fed infants, with high levels associated with improved health. However, in many cases the mechanisms underlying these beneficial effects are unknown, although a limited number of studies have suggested that bacteriocin production byBifidobacteriummay represent a key mechanism for preventing pathogen over-growth. Here, we used BAGEL4 and antiSMASH to identify putative bacteriocin sequences in the whole genome sequences of 33Bifidobacteriumstrains isolated from infants participating in two clinical studies. We identified a novel non-lantibiotic bacteriocin fromBifidobacterium longumsubsp.infantisLH_664, with 40% sequence homology to Lactococcin 972 fromLactococcus lactissubsp.lactis. The putative bacteriocin (Bifidococcin_664) was chemically synthesized and studied for antimicrobial and immune-modulatory activities. We determined it has discrete activity againstClostridium perfringensand it appears to have novel immune stimulatory activities, promoting macrophage phagocytosis and specific cytokine release. These data highlight strain-specific beneficial properties in the early life genusBifidobacterium, and suggest avenues for development of novel and highly specific dual action antimicrobials, and possible probiotic strains, that are active against clinically important bacterial pathogens.Data summarySamples LH_9 to LH_666 were previously sequenced and deposited to ENA under accession numbers ERS2658025-ERS2658043. Samples LH_986 to LH_1052 are newly sequenced and deposited to NCBI under accession numbers SAMN24838598-SAMN24838611. Additionally, previously assembled publicly available sequences (n=7) were retrieved online from NCBI Genomes database. See Supplementary Table S1 for further details.
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影响因子: --
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影响因子: --
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影响因子: 5.5
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