Increased sensitivity of Aggregatibacter actinomycetemcomitans to human serum is mediated by induction of a bacteriophage.

Increased sensitivity of Aggregatibacter actinomycetemcomitans to human serum is mediated by induction of a bacteriophage.
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DOI:
10.1111/omi.12378
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发表时间:
2023-02
影响因子:
3.7
通讯作者:
Mintz, Keith P.
Mintz, Keith P.
中科院分区:
医学3区
文献类型:
--
作者:
Tang-Siegel, Gaoyan G.;Chen, Casey;Mintz, Keith P.

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伴放线聚集菌是一种革兰氏阴性口腔病原体,可引起侵袭性牙周炎和全身感染,表现出血清耐药性。我们已经鉴定出一种带 dsDNA 尾的噬菌体 S1249,它可以由人血清诱导的这种微生物转化为裂解状态以杀死细菌。当该噬菌体暴露于人血清时,表现出活跃的转录物:与不存在人血清的细菌相比,当细菌在人血清存在下生长时,20%的基因上调超过10倍,其中45%的基因上调5-10倍。在马血清中生长时的转录激活不太明显。该噬菌体的尾巴具有内部刚性管和外部收缩鞘,这是肌病毒科的特征。进一步的表征表明,A. actinomycetemcomitans 染色体中噬菌体的溶原性整合发生在编码冷休克 DNA 结合结构域蛋白 (csp) 和谷氨酰-tRNA 合成酶 (gltX) 的基因之间。在感染的细菌中鉴定出噬菌体DNA整合的溶原性和非整合的假溶原性。使用这种噬菌体的新生成的溶原化菌株显示出相似的属性,包括在人血清存在下与其同基因无噬菌体菌株相比,生长抑制率为 63%。我们的数据表明,噬菌体 S1249 可以在人血清存在下被诱导并进入裂解周期,从而降低体内感染细菌的活力。
Aggregatibacter actinomycetemcomitans, a Gram‐negative oral pathobiont causing aggressive periodontitis and systemic infections, demonstrates serum resistance. We have identified a dsDNA‐tailed bacteriophage, S1249, which was found to convert from this microorganism inducible by human serum into a lytic state to kill the bacterium. This phage demonstrated active transcripts when exposed to human serum: 20% of genes were upregulated more than 10‐fold, and 45% of them were upregulated 5–10‐fold when the bacterium was grown in the presence of human serum compared to without the presence of human serum. Transcriptional activation when grown in equine serum was less pronounced. This phage demonstrated a tail with inner rigid tubes and an outer contractile sheath, features of Myoviridae spp. Further characterization revealed that the lysogenized integration of the phage in the chromosome of A. actinomycetemcomitans occurred between the genes encoding cold‐shock DNA‐binding domain‐containing protein (csp) and glutamyl‐tRNA synthetase (gltX). Both phage DNA integrated lysogeny and nonintegrated pseudolysogeny were identified in the infected bacterium. A newly generated, lysogenized strain using this phage displayed similar attributes, including 63% growth inhibition compared to its isogenic phage‐free strain when in the presence of human serum. Our data suggest that bacteriophage S1249 can be induced in the presence of human serum and enters the lytic cycle, which reduces the viability of infected bacteria in vivo.
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发表时间: 2021-11-11
期刊: Viruses
影响因子: --
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