Article(id=1194684380309327913, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1194684377813717012, articleNumber=null, orderNo=null, doi=10.13343/j.cnki.wsxb.20250328, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1745164800000, receivedDateStr=2025-04-21, revisedDate=null, revisedDateStr=null, acceptedDate=1747238400000, acceptedDateStr=2025-05-15, onlineDate=1762764552428, onlineDateStr=2025-11-10, pubDate=1762185600000, pubDateStr=2025-11-04, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1762764552428, onlineIssueDateStr=2025-11-10, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1762764552428, creator=13701087609, updateTime=1762764552428, updator=13701087609, issue=Issue{id=1194684377813717012, tenantId=1146029695717560320, journalId=1192105938417971205, year='2025', volume='65', issue='11', pageStart='4721', pageEnd='5182', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1762764551833, creator=13701087609, updateTime=1762764551833, updator=13701087609, preIssue=null, nextIssue=null, ext=null, issueFiles=null}, startPage=4817, endPage=4826, ext={EN=ArticleExt(id=1194684380984610860, articleId=1194684380309327913, tenantId=1146029695717560320, journalId=1192105938417971205, language=EN, title=Research progress in bacterial immune system defense against mobile genetic elements, columnId=1192149543727808575, journalTitle=Acta Microbiologica Sinica, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Mobile genetic elements drive bacterial evolution, while exposing bacteria to the risk of invasion by “selfish genes”. In the arms race with mobile genetic elements, bacteria have evolved a range of immune systems that can protect hosts from invading nucleic acids. These immune systems are capable of preventing the invasion of mobile genetic elements, degrading invading nucleic acids, inhibiting the replication or transcription of invading nucleic acids, or inducing abortive infections to protect the population. Although much is known about the working mechanisms of these host immune systems, it remains unclear how bacteria orchestrate different defense strategies in response to different stages of nucleic acid invasion. Based on our research and different immune strategies of bacteria to limit mobile genetic elements in different spatiotemporal dimensions, this review summarizes and classifies the host immune systems. The elucidation of these multilayered immune mechanisms not only reveals the arms race between host and mobile gene elements in the evolutionary process but also underpins the development of new biotechnologies.

, correspAuthors=Dongchang SUN, authorNote=null, correspAuthorsNote=
*E-mail:
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移动基因元件在驱动细菌进化的同时也使细菌面临“自私基因”入侵的风险。细菌在与移动基因元件的博弈过程中进化出一系列免疫策略,可增强宿主对入侵核酸的免疫力。这些免疫系统能够阻碍遗传物质入侵,降解入侵核酸,抑制入侵核酸的复制或转录,或引发流产感染,从而保护种群。尽管对宿主免疫系统的机制已有诸多了解,但目前仍不清楚细菌如何调配不同防御策略以应对不同阶段的入侵核酸。本文结合本课题组的研究,总结并归类了细菌在不同时空维度应对移动基因元件的策略。阐明这些多层次的宿主免疫机制,不仅揭示了进化过程中宿主与移动基因元件的博弈,也为未来开发新的生物技术提供了依据。

, correspAuthors=孙东昌, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=pYkGZ1r1r0FSVBCEtuII2Q==, magXml=5jCkOP5E2vyq+nRZciT4uA==, pdfUrl=null, pdf=/UpClZBUE2R9t7IRVrsfyg==, pdfFileSize=1565183, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=CfteqZXKfVmTD9bZm419Sg==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=psOtZLsrVGBWMU+4pIxrMA==, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=费明月, 孙东昌)}, authors=[Author(id=1194980257896841539, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1194684380309327913, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1194980257976533317, 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Several host immune systems involved in Abi

, figureFileSmall=null, figureFileBig=null, tableContent=
Host immune systemSensorEffectorAbortive infection
Gabija systemNTP and dNTP depletionNuclease (GajA)DNA degradation
CBASS systemCyclic oligonucleotide signalsNuclease, phospholipases, etc.Membrane impairment and NAD+ depletion
Pycsar systemCyclic oligonucleotide signalsOligonucleotide cyclase enzymesMembrane impairment and NAD+ depletion
Thoeris defense systemCyclic oligonucleotide signalsThsANAD+ depletion
DSRs systemDSR2 increaseDSR2NAD+ depletion
Toxin-antitoxin systemTurnover of the labile antitoxin or antitoxin deactivationProtein toxin or RNA toxinMembrane impairment, NAD+ depletion and DNA degradation
bGSDMs systemUnknownCaspase-like proteasesMembrane impairment
Long-B and Short pAgosGuide RNA recognizes invading DNApAgos and other effector proteinsMembrane impairment and NAD(P)+ depletion
Type III CRISPR-Cas systemRecognition of phage-transcribed RNA and cyclic oligonucleotidesCRISPR-associated proteinsRNA degradation and ATP depletion
Retrons systemPhage infection disrupts the RetronsRetronsToxin increase
Lamassu systemUnknownNucleases, proteases, etc.DNA degradation and NAD+ depletion
), ArticleFig(id=1194980260186931543, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1194684380309327913, language=CN, label=表1, caption=

参与Abi的几种宿主免疫系统

, figureFileSmall=null, figureFileBig=null, tableContent=
Host immune systemSensorEffectorAbortive infection
Gabija systemNTP and dNTP depletionNuclease (GajA)DNA degradation
CBASS systemCyclic oligonucleotide signalsNuclease, phospholipases, etc.Membrane impairment and NAD+ depletion
Pycsar systemCyclic oligonucleotide signalsOligonucleotide cyclase enzymesMembrane impairment and NAD+ depletion
Thoeris defense systemCyclic oligonucleotide signalsThsANAD+ depletion
DSRs systemDSR2 increaseDSR2NAD+ depletion
Toxin-antitoxin systemTurnover of the labile antitoxin or antitoxin deactivationProtein toxin or RNA toxinMembrane impairment, NAD+ depletion and DNA degradation
bGSDMs systemUnknownCaspase-like proteasesMembrane impairment
Long-B and Short pAgosGuide RNA recognizes invading DNApAgos and other effector proteinsMembrane impairment and NAD(P)+ depletion
Type III CRISPR-Cas systemRecognition of phage-transcribed RNA and cyclic oligonucleotidesCRISPR-associated proteinsRNA degradation and ATP depletion
Retrons systemPhage infection disrupts the RetronsRetronsToxin increase
Lamassu systemUnknownNucleases, proteases, etc.DNA degradation and NAD+ depletion
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细菌免疫系统防御移动基因元件的研究进展
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费明月 , 孙东昌 *
微生物学报 | 综述 2025,65(11): 4817-4826
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微生物学报 | 综述 2025, 65(11): 4817-4826
细菌免疫系统防御移动基因元件的研究进展
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费明月, 孙东昌*
作者信息
  • 浙江工业大学 生物工程学院,浙江 杭州
Research progress in bacterial immune system defense against mobile genetic elements
Mingyue FEI, Dongchang SUN*
Affiliations
  • College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, China
出版时间: 2025-11-04 doi: 10.13343/j.cnki.wsxb.20250328
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移动基因元件在驱动细菌进化的同时也使细菌面临“自私基因”入侵的风险。细菌在与移动基因元件的博弈过程中进化出一系列免疫策略,可增强宿主对入侵核酸的免疫力。这些免疫系统能够阻碍遗传物质入侵,降解入侵核酸,抑制入侵核酸的复制或转录,或引发流产感染,从而保护种群。尽管对宿主免疫系统的机制已有诸多了解,但目前仍不清楚细菌如何调配不同防御策略以应对不同阶段的入侵核酸。本文结合本课题组的研究,总结并归类了细菌在不同时空维度应对移动基因元件的策略。阐明这些多层次的宿主免疫机制,不仅揭示了进化过程中宿主与移动基因元件的博弈,也为未来开发新的生物技术提供了依据。

宿主免疫系统  /  移动基因元件  /  水平基因转移

Mobile genetic elements drive bacterial evolution, while exposing bacteria to the risk of invasion by “selfish genes”. In the arms race with mobile genetic elements, bacteria have evolved a range of immune systems that can protect hosts from invading nucleic acids. These immune systems are capable of preventing the invasion of mobile genetic elements, degrading invading nucleic acids, inhibiting the replication or transcription of invading nucleic acids, or inducing abortive infections to protect the population. Although much is known about the working mechanisms of these host immune systems, it remains unclear how bacteria orchestrate different defense strategies in response to different stages of nucleic acid invasion. Based on our research and different immune strategies of bacteria to limit mobile genetic elements in different spatiotemporal dimensions, this review summarizes and classifies the host immune systems. The elucidation of these multilayered immune mechanisms not only reveals the arms race between host and mobile gene elements in the evolutionary process but also underpins the development of new biotechnologies.

host immune systems  /  mobile genetic elements  /  horizontal gene transfer
费明月, 孙东昌. 细菌免疫系统防御移动基因元件的研究进展. 微生物学报, 2025 , 65 (11) : 4817 -4826 . DOI: 10.13343/j.cnki.wsxb.20250328
Mingyue FEI, Dongchang SUN. Research progress in bacterial immune system defense against mobile genetic elements[J]. Acta Microbiologica Sinica, 2025 , 65 (11) : 4817 -4826 . DOI: 10.13343/j.cnki.wsxb.20250328
水平基因转移(horizontal gene transfer, HGT)是移动基因元件(mobile genetic elements, MGEs)通过转化、转导和接合的方式在物种间传播[1]。细菌通过HGT获取来自噬菌体、质粒和其他物种基因组的遗传物质适应变化的环境,然而细菌在通过获取MGEs获得新性状、增强环境适应能力的同时也面临着“自私基因”入侵的风险[2],例如噬菌体对宿主菌的裂解[3],以及温和噬菌体、质粒存在于宿主内带来的代谢负担[4]。为此,细菌进化出了多样的宿主防御机制,采取多种手段应对MGEs的入侵。本文聚焦于宿主防御机制,基于细菌针对不同入侵阶段MGEs的防御策略,并结合本课题组研究结果对细菌的宿主防御机制进行系统性总结和分类。
噬菌体感染的初始步骤是其尾部蛋白吸附至宿主细胞特定的表面受体[5]。因此,膜表面修饰构成了宿主抵御噬菌体的“第一道防线”。宿主主要采取3种策略阻止噬菌体吸附:下调受体蛋白表达水平、产生受体蛋白突变体以及对受体蛋白进行阻断和掩盖。
当细菌处于高密度时面临噬菌体入侵的风险显著增高[6]。部分细菌通过群体感应机制调控受体蛋白的表达水平,以降低噬菌体感染的风险。例如,在大肠杆菌(Escherichia coli)中λ噬菌体的受体蛋白LamB受群体感应信号调控[7]。在鳗利斯顿氏菌(Listonella anguillarum) (曾用名Vibrio anguillarum)中群体感应系统可切换2种噬菌体防御模式:在低细胞密度时KVP40噬菌体的受体蛋白OmpK呈高表达,但宿主通过增加生物膜的形成减少噬菌体入侵的风险;随着细胞密度的增高OmpK表达受群体感应信号下调[8]。大量噬菌体受体蛋白的非同义突变体,以及自然群体中免疫噬菌体侵染菌株的受体突变体均表明宿主可通过突变受体蛋白降低噬菌体侵染的风险。如霍乱弧菌(Vibrio cholerae)中ICP2噬菌体受体蛋白OmpU的突变使细菌获得噬菌体的抗性[9]。此外,阻断或掩盖受体同样是免疫噬菌体的重要方式:E. coli通过F质粒编码的脂蛋白TraT修饰噬菌体受体蛋白OmpA构象[10];金黄色葡萄球菌(Staphylococcus aureus)产生一种蛋白A掩盖噬菌体受体来阻止噬菌体吸附[11];荧光假单胞菌(Pseudomonas fluorescens)通过合成藻酸盐形成黏液样菌落,从而赋予宿主抗噬菌体的能力[12]
膜表面修饰还可与其他免疫防御机制协同作用降低水平基因转移带来的风险。在沙雷氏菌属(Serratia)细菌中,抗生素压力激活Rcs磷酸传递系统,通过对膜结构修饰增强了对噬菌体的免疫能力;同时,Rcs磷酸传递系统抑制了宿主体内的3种CRISPR-Cas系统,从而提高了从接合转移中获取抗生素抗性的可能性[13]。这种防御策略既降低了宿主被噬菌体入侵的风险,又通过提高获取新性状的机会,提升了宿主的环境适应能力。
微生物中最为广泛和丰富的防御机制是特异性地识别和切割入侵核酸。当MGEs突破“第一道防线”入侵宿主时,宿主防御系统会第一时间对其识别并降解(图1),形成保护宿主的“第二道防线”。
限制性修饰系统(restriction-modification systems,R-M系统)通过区分宿主“自我”和“非自我” DNA,并利用核酸酶降解“非自我” DNA[14]。R-M系统在原核生物中分布广泛,约95%已测序的细菌和古菌中均有发现该系统[15-16]。R-M系统通常由甲基转移酶(methyltransferases, MTases)和限制性核酸酶(restriction endonucleases, REases) 2种组分组成,前者在特定的核酸位点对宿主DNA进行甲基化修饰,后者识别DNA的甲基化状态并切割未经修饰的DNA[17]
根据甲基转移酶和限制性核酸酶的亚基组成、识别位点特征和切割机制的差异可将R-M系统分为I-IV 4种类型。其中I-III型R-M系统降解未经修饰的外源DNA,而IV型系统则特异性切割经甲基化或其他化学修饰的DNA。具体而言,I型R-M系统的限制性修饰酶识别未经甲基化修饰的DNA后,在远离识别序列1 000 bp范围之内的区域发生随机切割[18]。II型R-M系统识别特定的回文序列,并在识别位点或附近区域进行精准切割[19]。由于其精准切割的特性,II型R-M系统的REases被开发成为基因工程中常用的工具酶。III型R-M系统切割位点在识别序列下游25-27 bp处,不同于II型R-M系统,其识别序列通常是非对称结构[20]。不同于I-III型R-M系统,IV型R-M系统识别并切割包括但不限于甲基化或磷酸化修饰的DNA[21]
CRISPR-Cas系统由成簇规律间隔短回文重复序列(clustered regularly interspaced short palindromic repeats, CRISPR)及其相关蛋白(CRISPR-associated proteins, Cas)组成。CRISPR-Cas系统分布广泛,在42%的细菌和85%的古菌中均被发现[22]。CRISPR-Cas系统是一种“适应性”免疫机制,能够通过保留特定的核酸序列实现对入侵核酸的记忆[23]。当相似核酸再次入侵时,CRISPR-Cas系统能对其特异性识别并靶向切割。由于CRISPR-Cas系统特异性切割核酸的特性,它已被开发为多种基因编辑[24]和防御耐药基因[35]的工具。
CRISPR-Cas系统对外源核酸的免疫主要有适应、表达和干扰3个阶段。在适应阶段负责获取外源DNA的适应复合物(如Cas1-Cas2蛋白复合体),将入侵的MGEs加工成为短片段并整合至CRISPR阵列的5′端形成新的间隔区[26]。CRISPR阵列作为对MGEs入侵的“免疫记忆库”,当与“免疫记忆”相似的MGEs再次入侵时,CRISPR基因座和CRISPR阵列表达(表达阶段),产生Cas相关蛋白和前体CRISPR RNA (crRNA),前体crRNA由Cas相关蛋白加工成为成熟crRNA。在干扰阶段,成熟crRNA与效应Cas蛋白组装形成效应复合物,由成熟crRNA引导,通过碱基互补配对识别靶标核酸,在Cas效应蛋白作用下降解靶标核酸[27-28]
根据效应复合物的结构将CRISPR-Cas系统分为1类系统(Class 1)和2类系统(Class 2)两大类[22,29]。1类CRISPR-Cas系统的效应蛋白由多亚基组成的Cas蛋白复合物构成,其中又细分为I型、III型和IV型;2类CRISPR-Cas系统的效应模块为单个多亚基的蛋白(例如Cas9、Cas12和Cas13),其中包括II型、V型和VI型。I型、II型和V型CRISPR-Cas系统能够靶向切割DNA;VI型CRISPR-Cas系统(如Cas13)能够靶向切割RNA。III型CRISPR-Cas系统部分亚型(如III-B型)能够靶向RNA,部分亚型(如III-A型)能够靶向DNA;值得注意的是,IV型CRISPR-Cas系统通过DNA干扰实现对接合质粒的防御,而非依赖核酸酶对DNA直接切割[29]
CRISPR-Cas系统的持续表达会造成宿主的代谢压力并导致自身免疫。因此,CRISPR-Cas系统受到精密的调控[30]。当细菌面临MGEs入侵风险较低时CRISPR-Cas系统常处于低表达或沉默状态;当细菌面临MGEs入侵或具有较高风险时宿主通过感应环境信号[31]、膜蛋白压力[32]或利用体内的转录调控因子[33-34]激活CRISPR-Cas系统,降低外源核酸入侵的风险。
Argonautes蛋白(Agos)最初在真核生物(eukaryotes Agos, eAgos)中被发现,是RNA沉默的关键组分。随后,在细菌和古菌中也鉴定出同源的原核Agos蛋白(prokaryotic Agos, pAgos)[35]。pAgos由短的寡核苷酸(14-35 nt)介导,通过碱基互补配对识别特异性的核酸。根据蛋白结构域组成可将pAgos分为Long-A、Long-B和Short pAgos[36-37]。其中,Long-A和Long-B pAgos与eAgos具有类似的蛋白结构,均具有Middle (MID)、P-element-induced wimpy testis (PIWI)、N-terminal (N末端)和PIWI-Ago-Zwille (PAZ)结构域;而Short pAgos仅具有MID和PIWI结构域。值得注意的是,Long-B pAgos和Short pAgos的PIWI结构域存在关键位点突变,是无活性核酸酶的蛋白[37-38]。与eAgos依赖短的RNA (siRNA/miRNA)介导的RNA干扰不同,Long-A pAgos偏好利用小干涉DNA (small interfering DNA, siDNA),少数利用小干涉RNA (small interfering RNA, siRNA)靶向降解入侵的质粒或病毒。Long-A pAgos通过其PIWI结构域的核酸内切酶活性将入侵的质粒或噬菌体降解成小片段,实现对MGEs的防御[39-40]
在MGEs入侵后,宿主通过限制MGEs在体内的复制和转录(图2)形成了宿主防御水平基因入侵的“最后防线”,从而降低入侵的MGEs对宿主造成的危害。
噬菌体感染后,宿主可通过合成特定的小分子物质限制噬菌体复制。例如,链霉菌属(Streptomyces)细菌在噬菌体入侵后会合成蒽环类化合物(如阿霉素和柔红霉素),这些次生代谢产物能够嵌入噬菌体DNA并干扰其复制[41]
宿主还可通过特定的蛋白酶消耗噬菌体复制所需的核苷酸底物抑制其在体内增殖。例如,细菌的脱氧胞苷三磷酸脱氨酶和脱氧鸟苷三磷酸酶可分别将噬菌体DNA合成所需的脱氧胞苷三磷酸(deoxycytidine triphosphate, dCTP)和脱氧鸟苷三磷酸(deoxyguanosine triphosphate, dGTP)转化为脱氧尿嘧啶核苷酸(dUTP和dUMP)和脱氧鸟苷(dG)[42]。类似地,抗病毒胞苷脱氨酶(activation-induced cytidine deaminase, AvcID)通过耗尽宿主内游离脱氧胞苷核苷酸阻断噬菌体DNA合成所需的原料供应[43]
最近的研究发现,核结合蛋白(nucleoid-associated protein, NAP)通过结合入侵质粒并重塑其空间结构阻碍质粒的复制[44]。其中,组蛋白样类核结构(histone-like nucleoid structuring, H-NS)作为一种NAP能结合、弯折和桥联双链DNA (double stranded DNA, dsDNA)。H-NS结合并桥联入侵的质粒,使质粒形成紧密结构,从而阻碍复制的进行。进一步研究发现,大肠杆菌中的多种NAP和不同物种来源的NAP均存在类似作用,这暗示着NAP可通过对入侵质粒结构的修饰影响宿主对质粒转移的防御[44]。这可能是原核生物防御质粒转移的重要保守机制。
噬菌体感染后,宿主还可通过合成特定的小分子物质抑制转录的进行。例如,噬菌体入侵后链霉菌属(Streptomyces)细菌产生的氨基糖苷类抗生素可以阻断噬菌体入侵的早期步骤并抑制噬菌体DNA复制和转录[45]。原核蝰蛇蛋白(prokaryotic viperins, pVips)通过催化产生修饰的核苷酸,包括ddhCTP、ddhGTP和ddhUTP,竞争性结合噬菌体RNA聚合酶,从而阻断转录的进行[46]
异源沉默因子(xenogeneic silencer, XS)通过抑制外源DNA的转录降低宿主的代谢负担[47]。XS在多种细菌中被鉴定,根据其进化起源及其DNA结合结构域的差异可将其分为H-NS家族、MvaT家族和Lsr2家族3个不同的家族[47-48]。H-NS和MvaT家族成员广泛存在于α-、β-和γ-变形菌纲等革兰氏阴性菌中,而Lsr2家族成员几乎只存在于革兰氏阳性的放线菌属(Actinomyces)中。XS通过特异性识别并结合至宿主基因组或其他基因元件上水平转移而来的序列(AT富含特征),阻碍RNA聚合酶的结合,实现对外源基因的沉默[47]
噬菌体在宿主体内增殖会威胁整个微生物群体。为了保护整个群体,微生物进化出了一种特殊的防御策略——流产感染(abortive infection, Abi)[49]。不同于上文描述的防御机制,Abi是一种通过牺牲被感染个体以保护整个种群的利他机制。宿主检测到自身被“感染”后激活免疫机制,引起生长停滞或细胞死亡,从而阻断噬菌体在群体中的复制和扩散,这类防御机制被归类为Abi系统。Abi系统通常由感知元件和效应物组成,见表1。感知元件检测噬菌体入侵带来的信号(如代谢产物等),随后激活效应物(如核酸酶、蛋白酶、NAD酶等),最终引发细胞生长停滞或凋亡[50]
Abi是由多种免疫系统参与导致的同一免疫结果[50]。基于环核苷酸的抗噬菌体信号系统(cyclic nucleotide-based antiphage signaling system, CBBSS)、Pycsar系统和Thoeris防御系统能够感知噬菌体入侵产生的环状核苷酸信号,从而激活效应物,引发被感染宿主的膜蛋白损伤、DNA降解或烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide, NAD+)耗竭,最终导致Abi[42,51-52]。防御相关的沉默调节蛋白(defence-associated sirtuins, DSRs)系统与Thoeris防御系统相似,通过含有SIR2结构域的蛋白消耗NAD+。宿主感知噬菌体的衣壳蛋白,导致含有SIR2结构域的DSR2蛋白表达增加,这引起宿主体内NAD+耗竭,导致Abi [53]。噬菌体在宿主体内复制消耗NTP和dNTP,Gabija系统感知这一信号后通过GajA蛋白不加选择地对噬菌体和宿主基因组进行降解,导致细胞死亡[54]。毒素-抗毒素(toxin-antitoxin, TA)系统最初被证明用于维持质粒和应对环境压力[55]。后续研究表明TA系统也参与Abi防御噬菌体。当噬菌体入侵后会影响抗毒素水平,这使得蛋白毒素或RNA毒素的含量增高,引起细胞膜损伤、NAD+消耗或核酸降解,从而导致Abi[56]。不同于Long-A pAgos对入侵核酸的降解,Long-B和Short pAgos无法直接降解入侵核酸。Long-B和Short pAgos在短的寡核苷酸介导下靶向噬菌体,并通过与其他效应蛋白协同引发膜蛋白损伤或NAD(P)+耗竭,导致宿主细胞凋亡[57-58]。III型CRISPR-Cas系统同样被证明参与了Abi,噬菌体转录产生的RNA被III型CRISPR-Cas识别后,Cas10产生一种小分子第二信使环寡腺苷酸(cyclic oligoadenylate, cOA)。cOA分子结合并激活一种效应RNA酶(Csm6),Csm6不加选择地降解噬菌体和宿主RNA,导致细胞休眠,甚至死亡[59-60]。III型CRISPR-Cas系统还可通过识别入侵的核酸产生cOA激活腺苷脱氨酶降解ATP,导致ATP耗竭[61]。此外,bGSDMs系统、Lamassu系统、Retrons系统等免疫系统也被证明参与Abi[62-64],但其机制仍有待明确。
近年来,对免疫系统的研究让人们认识到细菌免疫系统的丰富性和机制的多样性。根据免疫系统应对入侵核酸的不同阶段可将其分为“三道防线”:影响细胞表面以防止噬菌体吸附和遗传物质注入的系统;直接降解入侵MGEs的系统;阻碍入侵核酸复制和转录的系统。如果这“三道防线”被突破,免疫系统会诱导细胞休眠或凋亡以保护整个种群。部分免疫系统具有高度特异性,如特定噬菌体受体的修饰[7-10]、CRISPR-Cas系统靶向特定核酸[27-28];而部分免疫系统可应对多种MGEs,如R-M系统切割外源核酸[14],Abi系统感应核酸入侵造成的代谢变化引发细胞凋亡[49-50]。在单个细菌中也存在着多种免疫系统,一些免疫系统被证明协同发挥作用[8,13]。这种策略扩大了宿主免疫防御的范围,提高了宿主在环境中的生存能力。
当前研究虽然已经阐明了众多宿主免疫系统的分子机制,但宿主如何调控免疫系统表达的认知仍有限。由于免疫系统的持续表达会对宿主造成代谢负担,宿主必须采用精密的免疫调控以控制免疫防御的成本。例如,CRISPR-Cas系统降解外源核酸的机制已有了深入了解[27-28],但部分菌株中CRISPR-Cas系统处于沉默状态,宿主如何响应外源核酸入侵并解除其抑制的调控机制仍未完全明确。Abi系统通过感知核酸入侵造成的代谢紊乱激活免疫效应物[50]。目前对其免疫系统的触发条件已有了初步认知,但仍需要更多研究来明确其激活途径以及鉴定其他可能的激活方式。
现代生物技术的发展推动了新型宿主免疫系统的发现。宿主免疫系统的研究成果为突破性的生物技术工具开发提供了关键理论支撑。例如,CRISPR-Cas系统被大量开发为基因编辑工具、转录调控工具和耐药基因防控工具[22-23]。pAgos系统展现了对核酸的剪切能力,为新一代生物技术工具的研发开辟了新的方向。对宿主免疫系统的深入研究,有利于更精准地理解细菌与移动基因元件的博弈,同时为新一代的生物技术开发和技术革新提供理论依据和新的思路。
费明月:文献检索与整理,以及绘图、全文撰写与修改;孙东昌:全文指导与修改。
作者声明不存在任何可能会影响本文所报告工作的已知经济利益或个人关系。
  • 国家自然科学基金(32170083)
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2025年第65卷第11期
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doi: 10.13343/j.cnki.wsxb.20250328
  • 接收时间:2025-04-21
  • 首发时间:2025-11-10
  • 出版时间:2025-11-04
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  • 收稿日期:2025-04-21
  • 录用日期:2025-05-15
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National Natural Science Foundation of China(32170083)
国家自然科学基金(32170083)
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    浙江工业大学 生物工程学院,浙江 杭州

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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