微生物学报  2022, Vol. 62 Issue (9): 3329-3344   DOI: 10.13343/j.cnki.wsxb.20220062.
http://dx.doi.org/10.13343/j.cnki.wsxb.20220062
中国科学院微生物研究所，中国微生物学会

文章信息

阎依超, 方园, 唐家全, 邹丽芳, 陈功友. 2022
YAN Yichao, FANG Yuan, TANG Jiaquan, ZOU Lifang, CHEN Gongyou.
植物病原细菌毒性调控网络的研究进展
Virulence regulation networks in plant pathogenic bacteria: a review
微生物学报, 62(9): 3329-3344
Acta Microbiologica Sinica, 62(9): 3329-3344

文章历史

收稿日期：2022-01-28
修回日期：2022-04-07
网络出版日期：2022-06-01
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引用本文
阎依超, 方园, 唐家全, 邹丽芳, 陈功友. 植物病原细菌毒性调控网络的研究进展[J]. 微生物学报, 2022, 62(9): 3329-3344.
Yan Yichao, Fang Yuan, Tang Jiaquan, Zou Lifang, Chen Gongyou. Virulence regulation networks in plant pathogenic bacteria: a review[J]. Acta Microbiologica Sinica, 2022, 62(9): 3329-3344.
植物病原细菌毒性调控网络的研究进展
阎依超 , 方园 , 唐家全 , 邹丽芳 , 陈功友     
上海交通大学农业与生物学院, 上海 200240
收稿日期：2022-01-28；修回日期：2022-04-07；网络出版日期：2022-06-01
基金项目：上海市科技兴农项目[沪农科创字(2019)第2-2号]
摘要：植物病原细菌通过复杂和精细的全局性调控网络来协调多个层面的毒性决定因子。在不同的植物病原细菌中，这些全局性的毒性调控网络控制着细菌的侵染策略、存活以及在面临寄主植物防卫系统的互作环境中实现成功侵染的病程。本文详细分析了植物病原细菌4个重要属(假单胞菌属、果胶杆菌属、黄单胞菌属和雷尔氏菌属)的模式病原菌主要的毒性调控系统，包括群体感应系统、双组分调控系统、转录激活调控子以及转录后、翻译后的调控机制。在此基础上，重点评价了一些模式菌株全局性毒性调控机制的异同点，总结了一些最新的研究进展，并绘制了精细的网络调控图。这些分析表明，虽然一些相同的调控系统控制着病原菌的毒性，但是在不同种以及种下的亚种或者致病变种中这些调控机制功能各异，对于病原菌全毒性的贡献也存在着明显的差异。
关键词：植物病原细菌    毒性调控网络    细胞群体感应系统    双组分调控系统    转录激活调控子    
Virulence regulation networks in plant pathogenic bacteria: a review
YAN Yichao , FANG Yuan , TANG Jiaquan , ZOU Lifang , CHEN Gongyou     
School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
Received: 28 January 2022; Revised: 7 April 2022; Published online: 1 June 2022
*Corresponding author: ZOU Lifang, E-mail: zoulifang202018@sjtu.edu.cn.
Foundation item: Supported by the Shanghai Agriculture Applied Technology Development Program, China (G20190202)
Abstract: Plant pathogenic bacteria coordinate multifaceted virulence determinants through some complex and delicate global regulation networks. In the diverse species, these networks dictate bacterial infection strategies, survival, and the success in infection in the presence of host plant defense systems. In this paper, the major virulence regulation systems in the model pathogens in four genera (Pseudomonas, Pectobacterium, Xanthomonas, and Ralstonia) of plant pathogenic bacteria were reviewed, including the quorum sensing, two-component regulatory systems, transcriptional activators, and post-transcription or post-translation regulation systems. Particularly, the similarities and differences in the virulence regulation mechanisms among some model strains were analyzed and related research was summarized. Moreover, virulence regulation networks for the four pathogen groups were plotted. The analysis suggested the different functions of the virulence regulation networks among different species, subspecies, or variants of the pathogens despite some common regulation subsystems.
Keywords: plant pathogenic bacteria    virulence regulation networks    quorum sensing    two-component regulatory systems    transcriptional activators    

植物病原细菌通过分泌多种毒性因子，干扰寄主植物正常的生理代谢过程或者抑制寄主植物的防卫反应，从而成功侵染其寄主植物。这些毒性因子通常包括胞外酶、胞外多糖、毒素、激素、脂多糖、黏附因子以及Ⅲ型效应蛋白等[1]。不同的植物病原细菌具有不同的病害发展特征和寄主范围。例如丁香假单胞菌(Pseudomonas syringae)引起叶斑症状[2]，稻黄单胞菌(Xanthomonas oryzae)引起叶枯症状[3]，它们具有较窄的寄主范围。胡萝卜软腐病菌(Pectobacterium carotovorum)和青枯雷尔氏菌(Ralstonia solanacearum)分别引起软腐和维管束的萎蔫症状，具有非常广泛的寄主范围[4‒5]。这些在病程和症状上的不同，都是由病原菌致病性和毒性相关基因的表达不同引起的，由精细的毒性调控网络控制的。

1 植物病原细菌毒性调控系统的特点

植物病原细菌的毒性调控具有一些共同的特点：(1) 细胞的群体感应具有保守性，在全局性调控网络中调控多个毒性相关表型；(2) 双组分信号转导系统，能够感知环境或者寄主来源的信号，通过磷酸化信号途径激活调控蛋白，调控下游靶标基因的表达；(3) 转录调控子或者sigma因子，能够在转录水平激活或者抑制基因的表达；(4) 转录后和翻译后调控机制，通过控制mRNA的稳定性或者通过调控靶标蛋白的稳定性来调控目标基因表达。

1.1 群体感应系统(quorum sensing，QS)

QS是指细菌自身能够产生可渗透性的信号分子，例如酰基化的高丝氨酸内酯类(acylated homoserine lactone，AHL)[6]和顺式11-甲基-2-十二碳烯酸(cis-11-methyl-2-dodecenoic acid，DSF)类信号分子等[7]，随着细菌群体增加，信号分子的浓度也相应增加，细菌能够感受这些信号分子，通过胞内的调控蛋白激活或抑制下游基因的表达来调节病原菌的毒性以及群体行为。

除木质部小菌属(Xylella)和黄单胞菌属(Xanthomonas)外，在大多数植物病原细菌中都存在AHLs类信号分子。它们的QS系统由LuxI和LuxR家族的2个蛋白组成，LuxI是AHL的合成酶，LuxR是含有2个结构域的转录调控子。在细胞内外自由穿梭的AHL能够结合LuxR的其中一个结构域，另一个(螺旋-转角-螺旋)结构域能够结合在目标基因启动子区的lux-box区域，同时招募RNA聚合酶(RNA polymerase, RNAP)，继而调控下游基因的表达[8]。Lux-box结构域一般为位于目标基因上游大约40 bp的长度约20 bp的DNA片段(图 1)[8]。超过70种革兰氏阴性植物病原细菌能够产生AHL，它们的分子结构相似，仅在脂肪酸链的长度上存在一定的区别(大多数是C4‒C18)[6]。果胶杆菌属(Pectobacterium)中的QS系统包括至少3个转录激活子(ExpR1、ExpR2和CarR)以及一个AHL的合成酶ExpI，其能够合成2类AHL信号分子3-oxo-C6-HSL和3-oxo-C8-HSL[9‒11]。在青枯雷尔氏菌(R. solanacearum)中，除含有AHL外，还存在一类3-羟基棕榈酸甲酯(3-hydroxy palmitic acid methyl ester，3-OH-PAME)的信号分子，胞外信号分子3-OH-PAME通过激活PhcA上调AHL介导的QS系统[12‒13]。在黄单胞菌属中，例如甘蓝黑腐病菌(X. campestris pv. campestris，Xcc)和水稻白叶枯病菌(X. oryzae pv. oryzae，Xoo)的QS信号分子为DSF家族群体感应信号分子(diffusible signal factor，DSF)，包括DSF、BDSF、CDSF和3个新成员顺式-10-甲基-2-十二碳烯酸(IDS/DSF-Ⅱ)、顺式-9-甲基-2-癸烯酸和顺式-2-十一碳烯酸[14]。Rpf (regulation of pathogenicity factors)基因簇负责DSF的合成、信号识别与传递。RpfF是DSF合成的关键酶，DSF能够被双组分信号传导系统RpfC/RpfG所识别，RpfG能够导致第二信使环二鸟苷单磷酸(cyclic-di-GMP)的降解，从而引起生物膜的扩散、细菌胞外多糖(extracellular polysaccharide，EPS)的增加，胞外酶增多和T3Se基因表达的改变等一系列细胞行为[15‒17]。最近的研究显示，在黄单胞菌中发现了DSF的周转机制，rpfB是一个脂肪酰基辅酶a连接酶，参与DSF信号的周转(turnover)[18]。

图 1 植物病原细菌AHLs介导的群体感应信号系统模式图 Figure 1 Model diagram of the AHLs-mediated QS system in plant pathogenic bacteria.
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1.2 双组分调控系统(two component signal transduction system，TCSTS)

TCSTS是细菌感知胞外信号最主要的传导系统之一，一般由具有跨膜结构的组氨酸激酶(histidine kinase，HK)和位于胞内的感应调控子(response regulator，RR)组成。HK根据其磷酸基团转移的模式分为3种类型(图 2)[19]：(1) 经典模式，HK膜外功能域感知外部信号，通过保守的组氨酸位点(H1)的自我磷酸化，将磷酸基团传递到RR的天冬氨酸残基(D1)上激活RR，磷酸化的RR能够招募RNAP结合在目标基因的启动子区域，调控下游靶标基因的转录(图 2A)。(2) 非经典模式，HK含有H1、D1和第二个组氨酸位点(H2)，RR含有第二个天冬氨酸残基(D2)，磷酸基团需要经过H1-D1-H2-D2共4步来传递(图 2B)。(3) 杂合模式，与非经典模式相似，不同点在于H2存在于一个中间的连接蛋白上(图 2C)。

图 2 植物病原细菌双组分调控系统模式图 Figure 2 Model diagram of the two-component signal transduction systems in plant pathogenic bacteria.
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随着更多植物病原细菌菌株全基因组序列的公布，许多双组分调控基因被发掘。目前，在假单胞菌属(Pseudomonas)中GacS/GacA[20]和CorS/CorR[21]研究得比较清楚；在R. solanacearum中，PhcS/PhcR[22]、VsrB/VsrC[23]、VsrA/VsrD[24]等研究得比较清楚，它们都通过形成双组分调控系统的方式调控下游基因的表达，从而影响病原菌的毒性、游动性、生物膜的形成以及胞外多糖的产生等。在Xanthomonas spp.中，已发现大量双组分调控因子基因(约92至121个)，主要分为5种类型：(1) RpfC/RpfG系统，QS系统的组成部分，通过感知DSF信号分子来调控毒性相关基因的表达[25]。(2) RavS/RavR系统，能够通过调控细菌胞内cyclic-di-GMP的浓度来控制毒性相关基因的表达[26]。(3) HrpG-HpaS系统，通过影响Ⅲ型分泌系统(type Ⅲ secretion system，T3SS)相关基因的表达来调节T3SS效应蛋白的分泌，从而控制细菌的毒性[27]。(4) VgrS/VgrR系统，主要通过感知胞外的渗透压和Fe3+浓度来调控相关毒性基因的表达，从而影响病原菌的毒性[28‒29]。(5) RaxH/RaxR和PhoP/PhoQ系统，是表达AvrXa21所必需的，参与AvrXa21/Xa21互作，并且正向调控raxSTAB操纵子和其他rax基因[30]。

1.3 AraC类调控子和sigma (σ)因子

在已解析的植物病原细菌毒性调控网络中，特别是涉及T3SS调控途径中，需要一些转录调控子(例如AraC类调控子)和σ因子。虽然P. syringae和Pectobacterium spp.的T3SS基因的表达不依赖于AraC类激活子，但是R. solanacearum (例如HrpB)和Xanthomonas spp. (例如Xcc和Xoo的HrpX)的AraC类调控子是T3SS基因表达的关键激活子。σ因子是RNAP的可解离亚基，特异识别启动子元件并调节转录起始。σ因子在植物病原细菌中广泛存在，其中σ70和σ54家族因子研究较多，σ70因子结合位点位于启动子‒35/‒10区域，σ54因子结合位点位于高度保守的‒24/‒12区域，在转录过程中不可或缺[31]。在P. syringae中一个胞质外功能(extracytoplasmic function，ECF) σ因子HrpL能够激活整个T3SS基因表达，并且发现另外2个σ因子RpoN (σ54)和RpoS (σ38)也直接或者间接参与调控T3SS基因的转录表达[32‒33]。在稻黄单胞菌(X. oryzae)中，虽然目前明确了HrpG能够调控HrpX，通过HrpX调控T3SS基因，但在HrpG的上游或者HrpG-HrpX的调控途径中是否存在σ因子仍处于未知状态。在Xoo和R. solanacearum中都存在2个σ因子RpoN1和RpoN2，它们对鞭毛相关的游动性和病原菌毒性起调控作用[34‒35]。

1.4 转录后和翻译后的调控机制

Rsm转录后调控机制在一些重要的植物病原细菌中都存在，可能在毒性调控中起着共同或者相似的作用，这个调节体系由调节蛋白RsmA、RsmC和小RNA rsmB组成。RsmA是主要的调控因子，能够结合在目的基因核糖体结合位点(ribosome-binding site，RBS)的附近，干扰目的mRNA的转录或导致其被RNA酶(RNase)降解[36]。在P. carotovorum中，RsmA不仅控制着最主要的毒性因子PCWDEs基因的表达，而且控制T3SS调节基因hrpL的mRNA稳定性，负调控T3SS基因的表达[37]。rsmB是一个小分子的mRNA，富含能够被RsmA结合的GGA发卡结构，与RsmA结合后能够中和RsmA的毒性，抑制RsmA对目的mRNA的降解，同时rsmB能够被GacS/GacA双组分系统调控[38]。RsmC能够正调控RsmA，负调控rsmB[39]，但是其上游的调控网络也有待于进一步解析。在Xanthomonas spp.中也存在rsmA的同源基因，在Xcc、Xoo和Xoc中，RsmA正调控EPS、胞外酶和T3SS基因的表达[40‒44]；在柑橘溃疡病菌(X. citri subsp. citri，Xcci)中，RsmA通过稳定主要调控基因hrpG的5′端非翻译区(5′ untranslated regions，5′ UTR)区域来正调控T3SS基因的表达[45]。在Xcc中鉴定到了一个类似于rsmB功能的小RNA rsmU，其能中和RsmA的作用[46]。这暗示，在Xanthomonas spp.中也存在类似Rsm转录后机制，但是该机制是否由类似于GacS/GacA双组分系统来调控，有待于进一步解析。

翻译后机制通过蛋白降解来进行，这个降解过程一般发生在细胞内，需要依赖于ATP的蛋白酶。这类蛋白酶包含有4大类：ClpAP/ ClpXP[47]、ClpYQ[48]、Lon[49]以及FtsH[50]，其中ClpXP和Lon蛋白在植物病原细菌中研究较多。ClpXP是一个双组分蛋白酶复合体，ClpP是一个丝氨酸蛋白酶，ClpX是一个伴侣蛋白，能够特异性结合ClpP降解的底物蛋白[51]。达旦提狄克氏菌(Dickeya dadantii)中，clpX和clpP基因突变后，病原菌在寄主大白菜上的毒性显著降低；在识别因子RssB的协助下，ClpXP能够特异性降解sigma因子RpoS，RpoS能够激活rsmA的表达，RsmA通过转录后的机制负调控T3SS基因和PCWDEs基因的表达[52]。因此，ClpXP能够正调控T3SS基因和PCWDEs这2类最重要的毒性相关基因的表达，促进病原菌的毒性。Lon是一个高度保守、ATP依赖性的丝氨酸蛋白酶，控制蛋白的翻转(turnover)和目标蛋白的特异性降解。在P. syringae中，Lon负调控T3SS基因的表达和病原菌毒性，lon基因缺失后，引起T3SS基因的组成型表达，对T3SS的负调控作用通过降解T3SS调控基因hrpL的转录激活子HrpR来实现[53]。在Xcci中发现，Lon蛋白的磷酸化调控HrpG和其下游T3SS基因的表达[54]。

2 主要植物病原细菌毒性调控网络 2.1 假单胞菌毒性调控网络

P. syringae能够侵染梨、苹果、猕猴桃和大豆等多种重要的经济作物，约40个致病变种已被鉴定[55]。例如，从1980年至今，由丁香假单胞菌猕猴桃致病变种(P. syringae pv. actinidiae)引起的猕猴桃细菌溃疡病在意大利、新西兰和中国等国家已造成了严重的经济损失[56]。

在P. syringae的整个毒性调控网络中，双组分系统GacA/GacS是一个全局性的调控系统，控制着T3SS、EPS、QS、转录后系统rsmB/rsmZ、非编码的RNA、毒素的产量、Ⅵ型分泌系统(T6SS)以及PseABC的射流系统(efflux system) (图 3)。GacA通过sigma因子RpoN调控HrpL，来控制T3SS基因的表达[32, 57]；同时，HrpL和sigma因子AlgU也能够调控冠菌素(coronation)的产量[58]。GacA通过AhlI控制EPS的产生[59]；通过sigma因子RpoS调控非编码P16 RNA的活性[60]，通过转录激活子SalA控制3种毒素(syringomycin、syringopeptin和syringolin)的产量、T6SS以及PseABC主动外排系统(efflux system)[61‒63]。AhlI/AhlR组成QS系统，负责合成AHL信号分子，同时控制EPS的产生[59]。双组分系统CorS/CorR能调控冠菌素的生物合成[21]。rsmB/rsmZ为转录后系统[64]，但是，在丁香假单胞菌番茄致病变种(P. syringae pv. tomato) DC3000中鉴定到5个RsmA的同源蛋白RsmA1‒RsmA5，其中RsmA2和RsmA3在调节T3SS、游动性、冠菌素(coronatine)、假单胞衍生的脂八肽(syringafactin)和藻朊酸盐(alginate)中起主要的作用[65]；在不同的培养条件下，RsmA2和RsmA3调控的下游基因存在交叉，也呈现差异[66]。已有研究表明Lon以翻译后的机制，通过降解转录激活子HrpR来负调控T3SS基因的表达[53]。

图 3 假单胞菌属代表菌株的毒性调控网络 Figure 3 Virulence regulatory network of representative strains of phytopathogenic Pseudomonas. EPS indicates extracellular polysaccharides.
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2.2 黄单胞菌毒性调控网络

Xanthomonas spp.细菌侵染大约400多种植物，包括124种单子叶植物和268种双子叶植物[67]。在中国的南方省份，Xoo引起的水稻白叶枯病，以及条斑病菌(X. oryzae pv. oryzicola，Xoc)引起的水稻条斑病是经济作物水稻上最重要的2种细菌性病害[68‒69]。5种植物病原黄单胞菌Xcc、Xoo、Xoc、Xcci和辣椒斑点病菌(X. campestris pv. vesicatoria，Xcv)的致病机理研究较多。Xcc和Xoo都定殖于维管束，引起系统性病害；而Xcci、Xcv和Xoc仅引起局部性病害。黄单胞菌中主要的毒性因子包括T3SE、EPS、LPS、胞外酶、Ⅳ型菌毛(type Ⅳ pili，T4P)以及一些细菌表面的黏附因子[1]。其中，最重要的毒性因子为T3SS，编码T3SS组成蛋白的基因缺失后，病原菌会丧失在寄主植物上的致病性和非寄主植物上激发过敏反应(hypersensitive response，HR)的能力。

在Xoo、Xoc和Xcci的毒性调控网络中，第二信使环二鸟苷酸(cyclic diguanylate monophosphate，c-di-GMP)位于调控的中心，其与全局性调控因子Clp直接或间调控胞外酶、EPS、T3SS等毒性相关基因的表达(图 4)。RpfF/RpfC/RpfG组成了QS系统，RpfF合成QS的信号分子DSF来进行细胞间的交流；双组分系统RpfC/RpfG能够感知DSF的浓度，通过磷酸化激活RpfG，RpfG能够降解细胞内第二信使c-di-GMP，也控制着生物膜的形成和游动性[25, 70‒72]。现有的研究暗示RpfB可能介导DSF的周转机制，其可能通过抵消RpfF的酶活，参与致病性的调控[14, 18, 73]。双组分系统RavS/RavR和PcrK/PcrR也参与c-di-GMP的降解[26, 74]。c-di-GMP能够与Clp结合，阻止Clp与其目标基因启动子区的结合[17]。Clp能够通过转录激活子Zur正调控EPS的产量，其调控T3SS和胞外酶基因表达的机理还有待于进一步明确。HrpG和HrpX是T3SS基因主要的调控子，HrpG为感应调控子，其上游应存在一个受体激酶[27]。现有研究显示，在Xcc中HrpG的受体激酶为HpaS[27]，但是在Xoo缺少完整的hpaS同源基因，是否在黄单胞菌中具有共同的受体激酶，需要更多的证据。双组分系统VgrS/VgrR和PhoQ/PhoP也显示正调控T3SS基因的表达[30, 75]。在Xcc和Xoo中，RsmA以转录后机制，正调控胞外酶、EPS和T3SS基因的表达，但是具体的机制有待于进一步揭示。在Xcci中，RsmA通过结合hrpG mRNA的5′ UTR区域正调控T3SS基因表达[45]；Lon能够通过翻译后机制，降解HrpG蛋白负调控T3SS基因的表达[54]。我们前期研究显示，在hrp诱导培养条件下，EPS和LPS相关基因(metB和wxoB)的缺失以及RpfC/RpfG和VgrS/VgrR的缺失能够上调hrpG的表达[76‒77]。最新的研究显示，Xoo的T4P组装复合蛋白组分PilN涉及正调控细菌的游动性、毒性以及T3SS基因的表达[78]，这个调控机制是否与c-di-GMP有关，有待于进一步揭示。这暗示，T3SS上游还有一些未知的调控机制有待于进一步解析。

图 4 黄单胞菌属代表菌株的毒性调控网络 Figure 4 Virulence regulatory network of representative strains of phytopathogenic Xanthomonas spp.. EPS indicates extracellular polysaccharides.
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2.3 雷尔氏菌毒性调控网络

Ralstonia spp.细菌属于土壤习居菌，可寄生和腐生，寄主范围广泛，能够侵染200多种植物，其中包括经济上重要的马铃薯、番茄、香蕉、烟草及花生等，主要引起寄主植物维管束系统性萎蔫症状。2005年，根据全世界140个菌株的地理来源结合基因组信息的分析，将青枯雷尔氏菌(Ralstonia solanacearum)划分为4个进化型(phylotype)，phylotype Ⅰ主要来自于亚洲，phylotype Ⅱ (ⅡA、ⅡAT、ⅡB)主要来自于美洲，phylotype Ⅲ来自于非洲，phylotype Ⅳ来自于印度尼西亚、澳大利亚和日本[79‒80]。

在青枯雷尔氏菌整个毒性调控网络中，PhcA作为全局性的调控因子，控制EPS、T3SS、胞外酶、QS系统以及噬铁素等多个毒性因子(图 5)[81]。雷尔氏菌存在2个QS系统，一类是PhcB/PhcS/PhcR系统，以3-OH-PAME为渗透性信号分子，PhcB是3-OH-PAME的合成酶，PhcS/PhcR为双组分调控系统[13]。当细菌浓度达到107 CFU/mL时，3-OH-PAME能够与PhcS结合，激活感应调控子PhcR，同时释放PhcA[13]。PhcA正调控另一个QS系统为SolR/SolI，SolI为QS信号分子AHLs的合成酶，SolR能够感知AHLs的浓度，调控aidA基因的表达[79‒80]。也有研究表明，sigma因子RpoS正调控solR的表达[82]。双组分系统PehS/PehR正调控游动性和胞外酶PehA，双组分系统VsrB/VsrC能够负调控PehA酶活，正调控EPS的产量[79, 83]。双组分系统VsrA/VsrD负调控游动性，正调控纤维素酶基因cbhA和定殖相关基因的表达，它也通过转录激活子XpsR正调控EPS产量[23]。PrhA能够感知来源于寄主植物的信号，将信号通过PrhR传递给sigma因子PrhI，PrhI通过转录激活子，正调控T3SS主要的调控基因hrpG，从而实现对T3SS的正调控作用[84]。最新的研究显示，T3SS基因的表达也受到T4P组装蛋白TapV的正调控，但是这个调控机制不依赖于T4P菌毛蛋白PilA[85]。

图 5 雷尔氏菌的代表菌株毒性调控网络 Figure 5 Virulence regulatory network of representative strains of phytopathogenic Ralstonia solanacearum. EPS indicates extracellular polysaccharides.
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2.4 果胶杆菌属毒性调控网络

Pectobacterium spp.原为欧文氏胡萝卜软腐病菌(Erwinia carotovora subsp. carotovora)，寄主范围很广泛，能够侵染从热带到温带地域范围内16个科的植物，主要引起寄主组织的软腐症状(maceration)[86]。它最主要的毒性因子为从Ⅱ型分泌系统(T2SS)分泌的胞壁降解酶(PCWDEs)，其中以果胶酶作用最明显[87]。虽然T3SS和QS系统对于毒性的贡献不显著，但是，推测可能在病原菌的早期侵染过程中起一定的作用[88]。

在P. carotovora整个毒性调控网络中，RsmA作为全局性的抑制子，通过转录后机制负调控PCWDEs基因的表达，以及通过降解sigma因子HrpL的mRNA来负调控T3SS基因的表达(图 6)[81]。另外，RsmA也能够负调控QS系统中信号分子AHLs的合成酶基因expI的表达。QS系统由ExpR1 & 2/ExpI组成，ExpI合成AHLs，AHLs能够与ExpR或者反馈调控rsmA基因的表达[9‒10]。AHLs能够通过转录调控子CarR正调控碳青霉烯(carbapenem)抗生素的合成[89]；同时，Hor家族转录激活子也能够正调控碳青霉烯的合成，以及正调控PCWDEs基因的表达[90]。在欧文氏菌属中，同样是通过GacA-GacS双组分系统的转录后调控机制，对细胞外蛋白表达水平进行调节[91]。RsmC能够正调控RsmA，负调控rsmB[92]。HrpX/HrpY双组分系统能够感知来自寄主和非寄主植物的信号，通过转录激活子HrpS和sigma因子HrpL组成的级联途径实现对T3SS的正调控作用[93]。此外，PehS/PehR双组分系统能正调控PCWDEs基因的表达[94]。

图 6 果胶杆菌代表菌株的毒性调控网络 Figure 6 Virulence regulatory network of representative strains of phytopathogenic Pectobacterium carotovora. PCWDEs indicates plant cell wall-degrading enzymes.
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3 结论和展望

植物病原细菌通过感知来自寄主植物、环境和QS信号，来协调其不同毒性相关基因的表达，从而表现出不同的致病表型。已有的研究证据表明，植物病原细菌的毒性调控网络以全局性调控因子或者依赖于QS调控为中心；双组分系统提供了来自于环境的输入信号，一些激活子或者sigma因子影响关键毒性因素，如T3SS或者PCWDEs基因的表达。但是，仍然有不少问题有待于研究：(1) 哪些寄主来源的信号能够激活T3SS基因的表达，不同属的细菌是否存在相似的机制, 这些信号在细菌的表面是如何被感知和传递的；(2) 为什么在不同属的病原细菌中，位于毒性调控网络中心的因子存在差异，在黄单胞菌中，位于中心的调控子是否为依赖于c-di-GMP的Clp，需要更多证据进行验证；(3) 在雷尔氏菌和黄单胞菌中都发现T4P组装蛋白能够调控T3SS基因的表达，但通过什么机制调控了T3SS，仍有待进一步研究，c-di-GMP是否参与T4P对T3SS的调控过程，也有待于进一步揭示；(4) Rsm转录后机制广泛存在于果胶杆菌、假单胞菌和黄单胞菌中，但rsmB同源基因或类似机制是否保守存在，也有待于进一步解析。随着生物信息学和结构生物学等学科的发展，对调控子的蛋白结构进行解析，深入研究调控子蛋白作用机制以及其在致病性中的作用，靶向调控子的作用靶点的防治策略将为细菌性病害的有效防治提供新见解和思路。

致谢

感谢上海交通大学农业与生物学院的李逸朗、黄梦桑、李颖、陈慧妍、梁靖聆、李子阳、高彦瑾和朗博在参考文献的搜集以及综述写作中给予的协助，感谢西南大学的张勇副教授在雷尔氏菌分型和毒性调控机理写作部分提供的宝贵意见。

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植物病原细菌毒性调控网络的研究进展
阎依超 , 方园 , 唐家全 , 邹丽芳 , 陈功友