Nat Commun:一种新出现的人畜共患细菌在免疫力低下的人群体内的演变

2021-07-26 haibei MedSci原创

最近,研究人员描述了驱动一个白细胞介素-12受体β1缺乏症患者的新兴人畜共患病病原体Bordetella hinzii菌的适应性进化的机制。

对遗传性免疫缺陷患者的慢性感染情况的研究,为了解细菌的适应性过程提供了有力的依据。大多数先前的工作都集中在已建立的人类病原体的宿主内进化,其中主要的进化选择压力包括抗生素压力和宿主免疫反应。这些研究表明,在宿主内部适应的条件下,可以看出很多一般的进化过程。

在某些情况下,由于进化的错配修复(MMR)缺陷或移动遗传元素的插入而导致的突变率升高已被证明有助于快速进化。由于假基因的形成和大型染色体缺失导致的基因组压缩的戏剧性例子也已被描述,这在某些情况下会导致致病性的丧失和明显的病原体-宿主关系的进化。

我们从这些关于宿主内部适应性的研究中得到的一个重要启示是,在慢性感染过程中发生的遗传修饰往往与那些在较长的进化时期内从广泛的宿主范围内出现的人类限制性病原体相似。

Bordetella hinzii菌是β-保护性细菌的一员,最初在家禽的呼吸道中被发现。虽然主要与非人类宿主有关,但Bordetella hinzii菌是百日咳杆菌的遗传亲属,是人类百日咳的病因。最近,人们认识到,在人畜共患病转移后,Bordetella hinzii菌能够引起人类的疾病,包括呼吸道感染、胆管炎、菌血症和心内膜炎。基于这些报告,Bordetella hinzii被认为代表了一种新出现的病原体,对人类有人畜共患的风险,鉴于其遗传亲属有能力引起人类流行病,并在人与人之间持续传播,其本身也值得仔细研究。

最近,研究人员描述了驱动一个白细胞介素-12受体β1缺乏症患者的新兴人畜共患病病原体Bordetella hinzii菌的适应性进化的机制。对45个月内从血液和粪便中培养出来的24个Bordetella hinzii菌的基因组测序显示,一个克隆系经历了广泛的宿主内遗传和表型的多样化。24个分离物中有20个在DNA聚合酶III的ε亚基活性位点上有一个E9G的替换,导致校对缺陷。在这个校对缺陷的支系中,出现了具有DNA修复基因突变和突变谱改变的多个品系,并在临床培养物中占据了12个月以上。

分离的DnaQ E9G中存在基因组多样性

三羧酸循环和葡萄糖生成途径的多种酶反复发生突变,表明Bordetella hinzii菌对人类环境的快速代谢适应。此外,过量的G:C>T:A转位表明,氧化应激在适应过程中形成了基因多样化

对此,研究人员提出,DNA校对活动的失活与潜在的宿主免疫缺陷导致的长期但次致命的氧化攻击相结合,促进了基因组的快速适应。这些发现表明,在人畜共患感染后,宿主的免疫表型在塑造病原体进化方面起着根本的作用。

 

原始出处:

A. Launay et al. In vivo evolution of an emerging zoonotic bacterial pathogen in an immunocompromised human host. Nature Communications (2021). 

 

 

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    2021-08-09 xjy13
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    2022-04-06 liye789132251
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    2022-03-16 oliver181
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    2021-08-13 liuli5079
  6. [GetPortalCommentsPageByObjectIdResponse(id=2054235, encodeId=e0162054235bc, content=<a href='/topic/show?id=6ed4289e250' target=_blank style='color:#2F92EE;'>#免疫力低下#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28972, encryptionId=6ed4289e250, topicName=免疫力低下)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/lGEyfsKnIkkH93xUPMrUUycLh2XOfJJsphwPsVqDx8somSOepIFy9QE0MVAwDW3AS7V1epJ4tbPL9ADJLicvm8A/132, createdBy=b5132500067, createdName=ms55066533437992, createdTime=Wed Nov 03 06:19:39 CST 2021, time=2021-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1717077, encodeId=e6f21e170777e, content=<a href='/topic/show?id=f8a98002eb1' target=_blank style='color:#2F92EE;'>#群体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80027, encryptionId=f8a98002eb1, topicName=群体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c0832353243, createdName=xjy13, createdTime=Mon Aug 09 23:19:39 CST 2021, time=2021-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885325, encodeId=d4fd1885325fc, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Apr 06 19:19:39 CST 2022, time=2022-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1745873, encodeId=4edd1e4587381, content=<a href='/topic/show?id=34a5666451b' target=_blank style='color:#2F92EE;'>#演变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66645, encryptionId=34a5666451b, topicName=演变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96a135615295, createdName=oliver181, createdTime=Wed Mar 16 15:19:39 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2088074, encodeId=d8b820880e4d1, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Fri Aug 13 03:19:39 CST 2021, time=2021-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1307737, encodeId=d252130e73772, content=<a href='/topic/show?id=85d2289e188' target=_blank style='color:#2F92EE;'>#免疫力#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28971, encryptionId=85d2289e188, topicName=免疫力)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3547346, createdName=dongjia2010, createdTime=Wed Jul 28 10:19:39 CST 2021, time=2021-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1002807, encodeId=3683100280e11, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210626/5ae82dabbf924cf68e4674a9d301962f/8652877e70d04614a6830859f6cee8b5.jpg, createdBy=98ec5527440, createdName=ms1000000193404886, createdTime=Mon Jul 26 19:33:50 CST 2021, time=2021-07-26, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=2054235, encodeId=e0162054235bc, content=<a href='/topic/show?id=6ed4289e250' target=_blank style='color:#2F92EE;'>#免疫力低下#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28972, encryptionId=6ed4289e250, topicName=免疫力低下)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/lGEyfsKnIkkH93xUPMrUUycLh2XOfJJsphwPsVqDx8somSOepIFy9QE0MVAwDW3AS7V1epJ4tbPL9ADJLicvm8A/132, createdBy=b5132500067, createdName=ms55066533437992, createdTime=Wed Nov 03 06:19:39 CST 2021, time=2021-11-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1717077, encodeId=e6f21e170777e, content=<a href='/topic/show?id=f8a98002eb1' target=_blank style='color:#2F92EE;'>#群体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80027, encryptionId=f8a98002eb1, topicName=群体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c0832353243, createdName=xjy13, createdTime=Mon Aug 09 23:19:39 CST 2021, time=2021-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885325, encodeId=d4fd1885325fc, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Apr 06 19:19:39 CST 2022, time=2022-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1745873, encodeId=4edd1e4587381, content=<a href='/topic/show?id=34a5666451b' target=_blank style='color:#2F92EE;'>#演变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66645, encryptionId=34a5666451b, topicName=演变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96a135615295, createdName=oliver181, createdTime=Wed Mar 16 15:19:39 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2088074, encodeId=d8b820880e4d1, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Fri Aug 13 03:19:39 CST 2021, time=2021-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1307737, encodeId=d252130e73772, content=<a href='/topic/show?id=85d2289e188' target=_blank style='color:#2F92EE;'>#免疫力#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28971, encryptionId=85d2289e188, topicName=免疫力)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3547346, createdName=dongjia2010, createdTime=Wed Jul 28 10:19:39 CST 2021, time=2021-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1002807, encodeId=3683100280e11, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210626/5ae82dabbf924cf68e4674a9d301962f/8652877e70d04614a6830859f6cee8b5.jpg, createdBy=98ec5527440, createdName=ms1000000193404886, createdTime=Mon Jul 26 19:33:50 CST 2021, time=2021-07-26, status=1, ipAttribution=)]
    2021-07-26 ms1000000193404886

    谢谢分享

    0

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