微生物学报

SS2 strains	Substrate proteins	Phosphorylation sites	Biological characteristics	Effect on virulence of deficiency
SC19	STK (autophosphorylation)	Thr-167, Ser-175	Phosphorylated kinase, regulating downstream signal transduction	Decline
ZY05719	GlmM	Ser-101	Catalyses the synthesis of peptidoglycan precursors, maintaining cell wall integrity	Decline
ZY05719	BglF	Ser-462	PTS system components, regulating β-glucoside uptake and metabolism	Decline
05ZYH33	DivIVA	Ser-145, Thr-199, Thr-211	Regulating cell polarity and division, directing the localisation of cell wall hydrolases	Unknown
SC19	FtsZ	Thr-217, Thr-233, Thr-349, Thr-383	A key protein in cell division, forming Z-rings to direct spindle assembly	Unknown
SC19	MapZ	Thr-26, Thr-66	Localise cleavage sites, stabilise Z-rings, and regulate membrane contraction	Unknown
ZY05719	Ccps	Thr-4, Thr-7	Regulating the activity of tyrosine phosphatase CpsB, influencing capsular synthesis	Decline
05ZYH33	Cps2C	Unknown	Tyrosine kinase associated with capsular synthesis	Decline
ZY05719	GntR	Ser-41	Transcription factors regulating antioxidant stress-related genes (such as nox)	Decline
ZY05719	FadR	Thr-230	Transcription factors regulate the arginine deiminase (ADI) pathway, influencing acid tolerance	Decline
ZY05719	LacI	Thr-29	LacI family transcription factors, presumed to be involved in metabolic regulation	Unknown
05ZYH33	CovR	Thr-45, Thr-148, Thr-150, Thr-159, Thr-168, Thr-194, Thr-219, Ser-40, Ser-172, Ser-215, Thr-225	Systemic negative regulatory factor	Unknown
SC19	EF-P	Ser-148, Thr-176	Translation elongation factor, promoting polyproline protein synthesis	Decline
ZY05719	OsrP	Thr-48	Participation in antioxidant stress and maintenance of cell morphology	Decline

SS2 strains	Substrate proteins	Phosphorylation sites	Biological characteristics	Effect on virulence of deficiency
SC19	STK (autophosphorylation)	Thr-167, Ser-175	Phosphorylated kinase, regulating downstream signal transduction	Decline
ZY05719	GlmM	Ser-101	Catalyses the synthesis of peptidoglycan precursors, maintaining cell wall integrity	Decline
ZY05719	BglF	Ser-462	PTS system components, regulating β-glucoside uptake and metabolism	Decline
05ZYH33	DivIVA	Ser-145, Thr-199, Thr-211	Regulating cell polarity and division, directing the localisation of cell wall hydrolases	Unknown
SC19	FtsZ	Thr-217, Thr-233, Thr-349, Thr-383	A key protein in cell division, forming Z-rings to direct spindle assembly	Unknown
SC19	MapZ	Thr-26, Thr-66	Localise cleavage sites, stabilise Z-rings, and regulate membrane contraction	Unknown
ZY05719	Ccps	Thr-4, Thr-7	Regulating the activity of tyrosine phosphatase CpsB, influencing capsular synthesis	Decline
05ZYH33	Cps2C	Unknown	Tyrosine kinase associated with capsular synthesis	Decline
ZY05719	GntR	Ser-41	Transcription factors regulating antioxidant stress-related genes (such as nox)	Decline
ZY05719	FadR	Thr-230	Transcription factors regulate the arginine deiminase (ADI) pathway, influencing acid tolerance	Decline
ZY05719	LacI	Thr-29	LacI family transcription factors, presumed to be involved in metabolic regulation	Unknown
05ZYH33	CovR	Thr-45, Thr-148, Thr-150, Thr-159, Thr-168, Thr-194, Thr-219, Ser-40, Ser-172, Ser-215, Thr-225	Systemic negative regulatory factor	Unknown
SC19	EF-P	Ser-148, Thr-176	Translation elongation factor, promoting polyproline protein synthesis	Decline
ZY05719	OsrP	Thr-48	Participation in antioxidant stress and maintenance of cell morphology	Decline

猪链球菌2型丝氨酸/苏氨酸激酶磷酸化底物的生物学功能

PDF下载

田羽彤 ¹ , 颜茹 ¹ , 尹航 ¹ , 赵紫轩 ¹ , 郎诗琪 ¹ , 方仁东 ¹^,²

微生物学报 | 综述 2026,66(7): 3203-3218

收起

微生物学报 |综述 2026 , 66 (7) : 3203 -3218

猪链球菌2型丝氨酸/苏氨酸激酶磷酸化底物的生物学功能

全屏

田羽彤¹, 颜茹¹, 尹航¹, 赵紫轩¹, 郎诗琪¹, 方仁东¹^,²

作者信息

^1.西南大学动物医学院，动物健康与动物性食品安全国际联合实验室，重庆

^2.国家生猪技术创新中心，重庆

作者简介:

作者贡献声明

田羽彤：构思与撰写；颜茹：撰写；尹航：修改；赵紫轩：文献查找与分析；郎诗琪：图标制作；方仁东：文章构思与写作指导。

Biological functions of serine/threonine kinase phosphorylation substrates in Streptococcus suis serotype 2

Yutong TIAN¹, Ru YAN¹, Hang YIN¹, Zixuan ZHAO¹, Shiqi LANG¹, Rendong FANG¹^,²

Affiliations

^1.Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, China

^2.National Center of Technology Innovation for Pigs, Chongqing, China

出版时间: 2026-07-04 doi: 10.13343/j.cnki.wsxb.20250786

文章导航

摘要

收起

猪链球菌(Streptococcus suis)是一种重要的人畜共患病病原体，既可感染猪，也可引发人类脑膜炎等严重疾病。其致病性取决于迅速适应环境压力及宿主免疫反应的能力。丝氨酸/苏氨酸激酶及其对应的磷酸酶构成细菌中一类真核样信号转导系统，在猪链球菌2型中发挥关键调控作用，与其生物学特性及致病机制密切相关。丝氨酸/苏氨酸激酶/磷酸酶通过精确调控其下游底物的磷酸化与去磷酸化，形成复杂的信号网络，进而影响细菌的多种生理与致病过程。本文系统梳理并综述了目前已知猪链球菌2型中丝氨酸/苏氨酸激酶的底物，重点阐明该类激酶如何通过调控不同功能底物的磷酸化状态，精确调控细菌的生长分裂、荚膜合成、应激耐受、黏附侵袭以及致病力。本文旨在为深入理解猪链球菌2型的发病机制及开发新型抗菌策略提供新视角。

关键词

丝氨酸/苏氨酸激酶/磷酸酶 / 磷酸化修饰 / 猪链球菌2型 / 毒力 / 调控网络

Abstract

收起

Streptococcus suis is a major zoonotic pathogen that can infect both pigs and humans, causing severe diseases such as meningitis in humans. Its pathogenicity depends on the ability to rapidly adapt to environmental stress and host immune responses. Serine/threonine kinases and their corresponding phosphatases constitute a eukaryotic-like signal transduction system in bacteria and play a key regulatory role in S. suis serotype 2, closely related to its biological characteristics and pathogenic mechanisms. Through precise regulation of the phosphorylation and dephosphorylation of downstream substrates, serine/threonine kinases/phosphatases form complex signaling networks, thereby influencing various physiological and pathogenic processes of the bacterium. This article systematically reviews the currently known substrates of serine/threonine kinases in S. suis serotype 2, with a focus on elucidating how these kinases precisely regulate bacterial growth and division, capsule synthesis, stress tolerance, adhesion, invasion, and pathogenicity by modulating the phosphorylation status of functional substrates. This review aims to provide new perspectives for deciphering the pathogenic mechanism of S. suis serotype 2 and the development of novel antibacterial strategies.

Key words

serine/threonine kinase/phosphatase / phosphorylation / Streptococcus suis serotype 2 / virulence / regulatory network

引用本文

田羽彤, 颜茹, 尹航, 赵紫轩, 郎诗琪, 方仁东. 猪链球菌2型丝氨酸/苏氨酸激酶磷酸化底物的生物学功能. 微生物学报, 2026 , 66 (7) : 3203 -3218 . DOI: 10.13343/j.cnki.wsxb.20250786

Yutong TIAN, Ru YAN, Hang YIN, Zixuan ZHAO, Shiqi LANG, Rendong FANG. Biological functions of serine/threonine kinase phosphorylation substrates in Streptococcus suis serotype 2[J]. Acta Microbiologica Sinica, 2026 , 66 (7) : 3203 -3218 . DOI: 10.13343/j.cnki.wsxb.20250786

正文

收起

猪链球菌(Streptococcus suis)是一种革兰氏阳性球菌，是导致猪链球菌病的主要原因，可引发猪出现败血症、脑膜炎以及关节炎等多种疾病症状，给养殖业带来巨大经济损失^[1]。根据其荚膜多糖(capsular polysaccharide, CPS)抗原性的差异，S. suis可分为29个血清型^[2]，其中毒力最强、临床分离率最高的血清型为猪链球菌2型(Streptococcus suis serotype 2, SS2)^[3]。同时，S. suis也被证实是重要的人畜共患病原体，人感染后可表现为化脓性脑膜炎、感染性休克、听力损伤，甚至导致永久性神经功能损害，严重者会死亡，造成严重的公共卫生问题^[4-5]。目前，已报道多种SS2毒力因子，包括荚膜多糖、溶菌酶释放蛋白、溶血素、烯醇化酶等，这些毒力因子主要参与黏附、抗吞噬、侵袭以及炎症通路激活等过程，在逃避免疫识别、穿过血脑屏障等方面发挥重要作用^[6-9]。特别值得注意的是，S. suis破坏血脑屏障完整性是其致病性的关键环节。

蛋白质翻译后修饰(post-translational modification, PTM)作为调控蛋白质功能与活性的核心机制，在细胞感知外界信号和协调生命活动中发挥着重要作用^[10]。长期以来，PTM研究主要聚焦于真核生物，对原核生物PTM的认识相对有限^[11]。随着蛋白质组学与生物信息学的发展，研究发现多种病原菌的毒力因子存在广泛的PTM，这些修饰深刻影响细菌的蛋白质合成、能量代谢、休眠维持以及毒力基因表达等关键过程^[12-15]。蛋白质磷酸化是目前研究最为系统、机制最为明确的翻译后修饰之一，即使在原核生物(如细菌)中它同样是最受关注且研究最为深入的修饰类型^[16]。与真核生物不同，细菌的磷酸激酶与磷酸酶系统具有更高的多样性。通过可逆蛋白质磷酸化进行信号转导是原核生物和真核生物的关键调控机制^[17]，其中真核样丝氨酸/苏氨酸激酶(eukaryotic-like serine/threonine kinase, eSTK)和磷酸酶(serine/threonine phosphatase, STP)是细菌中一类最重要的磷酸化调控激酶/磷酸酶，参与调控细胞分裂、代谢、芽孢形成以及毒力产生等核心生物学过程^[18-19]。近年来，随着磷酸化蛋白质组学技术的应用，越来越多的eSTK底物蛋白在病原菌中被鉴定出来，这些功能各异的底物构成了eSTK介导的精细调控网络。在此背景下，本文聚焦SS2，总结回顾目前已知的SS2的丝氨酸/苏氨酸激酶(serine/threonine kinase, STK)磷酸化底物谱及分子调控机制，这将为揭示SS2的细胞生物学调控网络及其复杂致病机制提供理论依据。

1 猪链球菌2型STK的功能

收起

几乎所有革兰氏阳性菌中都至少存在1个STK，SS2所编码的STK为单拷贝stk基因产物，属于典型的跨膜蛋白，在调控细菌应激反应及毒力方面发挥着关键作用^[20-21]。该激酶的2个自磷酸化位点分别为Thr-167和Ser-175^[22]。STK通过介导底物蛋白丝氨酸(serine, Ser)与苏氨酸(threonine, Thr)残基的磷酸化修饰，广泛参与调控细菌的多种生理过程，涵盖生长与发育、生物被膜形成、细胞分裂、中心代谢与次级代谢、应激反应以及毒力等方面^[23]。早期杜骁杰等^[24]通过构建stk缺失株(Δstk)并进行转录组学分析，发现stk影响SS2中约24.8%的基因表达(544个基因)，其中33个基因转录水平上调，511个基因转录水平下调，表明stk在SS2中主要起正调控作用。与野生型SS2相比，Δstk生长速率减缓，全血存活能力下降，氧化应激能力减弱；然而，其对Triton X-100的抵抗能力增强，同时黏附能力与抗吞噬能力均减弱，整体毒力显著降低^[25]。

为探究猪链球菌SC19中STK蛋白及其靶磷酸化位点的潜在作用底物，研究人员对SC19和Δstk菌株进行磷酸化蛋白质组学分析，结果显示SC19与Δstk菌株间存在418种差异磷酸化蛋白，其中Δstk菌株相较于SC19有332种磷酸化蛋白磷酸化程度下调，86种磷酸化蛋白磷酸化程度上调；KEGG通路富集分析表明，这些下调磷酸化蛋白主要富集于核糖体、生物合成、嘧啶代谢、磷酸转移酶系统(phosphotransferase system, PTS)、氨基糖及核苷酸糖代谢、蛋白质输出、碳代谢、细菌分泌系统、戊糖磷酸途径等通路；GO通路富集分析显示，这些下调磷酸化蛋白在大分子生物合成过程、细胞氮化合物生物合成过程、基因表达调控、代谢过程调控、生物调控、DNA模板转录调控、初级代谢过程调控、肽代谢过程以及细胞过程调控等通路中显著富集^[26]。本文所综述的底物蛋白均包含在组学显示的磷酸化差异蛋白之中。

2 猪链球菌2型STK磷酸化底物的种类与功能

收起

SS2的STK可以通过调控下游底物蛋白的磷酸化调控自身的生长、代谢和毒力等。目前已报道多种STK通过调节下游底物蛋白的磷酸化来调节SS2生物学特性的方式(表1、图1)。

2.1 磷酸葡糖胺变位酶

磷酸葡糖胺变位酶(phosphoglucomutase, GlmM)可催化氨基葡萄糖-6-磷酸活化成氨基葡萄糖-1-磷酸，这是合成UDP-N-乙酰氨基葡萄糖(UDP N-acetyl-D-glucosamine, UDP-NAG)的早期步骤，而UDP-NAG是细胞壁肽聚糖的组成部分^[27]。原核生物独有的GlmM催化反应使GlmM成为有吸引力的治疗靶点。在SS2之前，GlmM的功能已在结核分枝杆菌(Mycobacterium tuberculosis)、金黄色葡萄球菌(Staphylococcus aureus)、枯草芽孢杆菌(Bacillus subtilis)、炭疽芽孢杆菌(Bacillus anthracis)、幽门螺杆菌(Helicobacter pylori)和大肠埃希氏菌(Escherichia coli)等细菌中分别得到揭示，如在M. tuberculosis中glmM的缺失会影响细胞壁的形态和厚度^[28]；在S. aureus中GlmM的失活会引起对甲氧西林的耐药性显著降低，以及对替考拉宁的敏感性增强^[29-30]；在B. subtilis中GlmM通过抑制CdaA的酶活性影响细菌对渗透压变化的适应能力等^[31]。在SS2中GlmM的STK磷酸化位点为Ser-101，缺失glmM或通过点突变(如Ser-101突变为丙氨酸)抑制其磷酸化后，SS2肽聚糖前体合成受阻，进而引起细胞壁结构异常，表现出细胞体积增大、荚膜多糖缺失、细胞分裂缺陷等形态学改变^[32]。此外，glmM缺陷株表现出多方面的生理功能受损，其对高渗透压、氧化胁迫及溶菌酶的耐受性均显著下降，同时在血液中的存活能力减弱，中性粒细胞对其清除作用增强，生物膜形成能力也受到明显抑制；上述缺陷共同削弱了该菌株在感染过程中的适应能力，最终导致其致病性显著降低。综合来看，STK通过激活GlmM在Ser-101处的磷酸化来控制SS2细胞壁肽聚糖的合成和毒力^[33]。

2.2 β-葡萄糖苷糖操纵子(beta-glucoside operon, Bgl) F

PTS是细菌中最普遍的糖转运系统，由酶I (enzyme I, EI)、热稳定的磷酸载体蛋白(histidine-containing phosphocarrier protein, HPr)和酶Ⅱ (enzyme Ⅱ, EII)等3个主要部分组成。E. coli的β-葡萄糖苷糖操纵子(beta-glucoside operon, Bgl)编码的蛋白质BglG、BglF和BglB组成一个典型的PTS系统，参与芳基β-葡萄糖苷的摄取、利用及其调控^[34]。BglF既是Bgl操纵子表达的负调节因子，也是参与β-葡萄糖苷摄取的磷酸转移酶^[35-36]。研究表明，PTS组分与细菌毒力有关，并将PTS鉴定为许多细菌的毒力因子^[37]。在SS2中BglF的STK磷酸化位点为Ser-462，缺失bglF或通过点突变(如Ser-462突变为丙氨酸)抑制其磷酸化后，SS2表现出全血存活能力、被膜形成能力、抗RAW264.7细胞吞噬、黏附侵袭率和毒力下降；通过改变代谢能力来适应不同的宿主环境是细菌在感染过程中的常用策略，SS2 STK能磷酸化BglF，调控细菌自身利用蔗糖和果糖的能力，从而影响细菌的生长^[33]。

2.3 细菌分裂蛋白DivIVA、FtsZ、MapZ

革兰氏阳性菌(G⁺)的细胞壁较厚，主要由丰富的肽聚糖层和磷壁酸组成，这对细菌的形态发生和致病性至关重要^[38-39]。细菌形态很大程度上取决于肽聚糖(peptidoglycan, PG)，肽聚糖是一种由聚糖链通过短肽交联形成的巨大网状结构，它包裹着细胞膜，提供机械强度以抵抗内部渗透压，并塑造了细菌千姿百态的外形^[40-41]。细菌肽聚糖的合成与组装是一个极其复杂且高度协调的过程，涉及数十种酶和辅助蛋白在时间与空间上的精密协作，其合成途径提供了丰富的新型抗菌药物靶点来源^[42]。

在众多参与细胞形态维持的蛋白中，DivIVA是一个在革兰氏阳性菌中高度保守的卷曲螺旋蛋白^[43]。它最初在枯草芽孢杆菌中被发现，核心特性是能够识别并结合到细胞膜上负曲率高的区域^[44]，如生长中的隔膜和细胞极，从而在这些位点聚集并调控下游因子，被认为是隔膜重塑的主要参与者^[45-46]。DivIVA蛋白的功能因细菌种类而异，在大多数细菌的细胞壁肽聚糖的合成和细胞分裂中发挥关键作用^[47]。在B. subtilis等细菌中Min系统负责定位细胞分裂的位置，DivIVA是Min系统的重要组成部分，通过抑制细胞极部的Z环组装以防止产生不对称分裂或无核细胞^[48]；在单核增生李斯特氏菌(Listeria monocytogenes)中divIVA的缺失引起严重的细胞分离缺陷，使得细菌分裂后仍连在一起，形成长链状^[49]；在M. tuberculosis中DivIVA (又称Wag31)是必不可少的，当Wag31功能受损时M. tuberculosis的极性生长受到严重抑制，导致细胞形态异常和生长缺陷^[50]。在SS2中DivIVA的STK磷酸化位点为Ser-145、Thr-199和Thr-211，缺失divIVA或通过点突变(如Ser-145、Thr-199或Thr-211突变为丙氨酸)抑制其磷酸化后，SS2会导致细胞壁水解酶MltG定位错误，从而使细菌伸长缺陷，形态更圆^[51-52]。值得注意的是，DivIVA并不直接影响MltG的酶活，而是通过控制其空间分布间接调控PG代谢^[53]。

在细菌中二分裂是最常见的细菌分裂方式，为此，细菌进化出不同的机制来选择分裂位点，并将微管蛋白样蛋白FtsZ定位在细胞中^[54]。FtsZ是大多数原核生物和许多真核细胞器中的主要细胞分裂蛋白，它是第一个定位到分裂位点的蛋白质，对于分裂体复合物的组装至关重要^[55]。在SS2中FtsZ的STK磷酸化位点为Thr-217、Thr-233、Thr-349和Thr-383，FtsZ的磷酸化位点在FtsZ的C端，而互作位点在FtsZ的N端。遗憾的是，FtsZ的磷酸化状态与猪链球菌细胞分裂之间的调控关系尚未深入研究^[56]。

MapZ作为细胞分裂关键蛋白^[57]，在S. suis的正确隔膜定位中发挥着重要作用。该蛋白缺失虽不影响细菌存活，却可导致细胞形态异常、分裂障碍及极小细胞的出现^[58]。在SS2中MapZ的STK磷酸化位点为Thr-26和Thr-66，研究发现将这2个位点分别突变为丙氨酸以抑制MapZ磷酸化后，突变菌株的隔膜仍能正确定位，提示MapZ的磷酸化仅在特定时空条件下影响分裂过程，可能通过干扰Z环稳定性进而引起形态异常。STK可能通过对MapZ的磷酸化修饰精确调控隔膜收缩时机；值得注意的是，磷酸化功能缺失的MapZ仍可与STK发生相互作用，表明二者间存在除磷酸化修饰外的其他结合界面^[59]。

2.4 荚膜多糖合成相关蛋白CcpS、Cps2C

荚膜多糖是S. suis关键的毒力因子，使其能够在宿主血液中存活，同时也是该菌血清型分类的主要依据^[60]。然而，CPS在S. suis致病机制中的具体作用，以及其所诱导的免疫反应在SS2感染过程中是否发挥保护功能目前仍存在争议。

CcpS能够直接与酪氨酸磷酸酶CpsB结合，进而影响CpsBCD磷酸调控系统的功能，在CPS合成调控中扮演关键角色。非磷酸化状态的CcpS对CpsB磷酸酶活性具有抑制作用，而STK介导的CcpS磷酸化则能解除该抑制，从而增强CpsB对CpsD的去磷酸化作用。CpsD作为Wzx-Wzy途径中负责CPS聚合的关键酪氨酸激酶，其磷酸化状态的精细调控直接影响SS2荚膜多糖的合成效率与输出^[61]。在SS2中CcpS的STK磷酸化位点为Thr-4与Thr-7，缺失CcpS或通过点突变(Thr-4或Thr-7突变为丙氨酸)抑制其磷酸化后，SS2表现出CPS产量显著下降、细胞表面荚膜厚度减小、对巨噬细胞吞噬的抵抗能力减弱，以及在小鼠感染模型中致病力明显降低^[62]。

虽然酪氨酸磷酸化在整个磷酸化事件中占比不高，但其在细菌的生长繁殖、应激反应及致病性等方面发挥着不可忽视的作用^[63]。以肺炎链球菌(Streptococcus pneumoniae)为例，其荚膜合成过程受跨膜调节蛋白CpsC及其胞内C末端与酪氨酸激酶CpsD的协同作用调控^[64]。cps2C基因位于荚膜合成基因座上游，编码的酪氨酸激酶Cps2C在S. suis的各个血清型中相对保守，与S. pneumoniae酪氨酸激酶CpsD具有较高相似性，属于其同源蛋白。单独的Cps2C蛋白并不具有激酶活性；将荚膜合成蛋白Cps2B的胞内C端23个氨基酸与Cps2C融合表达形成融合蛋白Cps2BctC，Cps2C被激活表现出激酶活性^[65]。在有STK存在的条件下，Cps2C能够被检测出苏氨酸磷酸化信号，证明STK可以磷酸化Cps2C蛋白，在SS2中存在STK信号酶和PTK信号酶的磷酸化反应^[66]。

2.5 转录因子GntR、FadR、LacI

转录因子(transcription factor, TF)是一类能与特定基因5′端上游的特定DNA序列结合，调控该基因转录的蛋白质分子^[67]。转录因子对细菌的生存至关重要，通过调节转录因子的磷酸化来调控SS2的生命活动，是STK的重要调控手段之一。

GntR家族转录因子广泛分布于细菌中，可参与各种代谢过程的调控。GntR家族转录因子分为7个亚家族，包括FadR、HutC、MocR、YtrA、AraR、DevA和PlmA。它们广泛参与S. pneumoniae荚膜多糖的合成和毒力调控、变异链球菌(Streptococcus mutans)糖转运蛋白的表达、生物膜的合成以及抗生素耐药性等方面^[68-69]。在SS2中GntR的STK磷酸化位点为Ser-41，缺失gntR基因或通过点突变(如将Ser-41突变为丙氨酸)抑制其磷酸化后，SS2对小鼠的致死性和致病性以及自身抗氧化能力显著降低。SS2的STK通过GntR的磷酸化抑制了nox基因的转录，这导致在氧化应激条件下还原型烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide, NADH)积累，高水平的NADH会过度激活电子传递链，导致电子泄漏增加，进而增加活性氧(reactive oxygen species, ROS)的杀伤作用。抗氧化应激能力受损可能是SS2毒力降低的关键原因^[70]。

FadR属于GntR家族，是GntR家族转录调节因子中最大的亚家族^[71-72]。FadR负调控编码参与脂肪酸β氧化和转运的蛋白质的基因表达，同时正调控参与脂肪酸生物合成的酶的基因表达^[73]。一些研究表明，FadR参与多种生理过程，这些过程可能对细菌适应环境至关重要^[74]。在SS2中FadR的STK磷酸化位点为Thr-230，缺失fadR基因或通过点突变(如将Thr-230突变为丙氨酸)抑制其磷酸化后，受感染小鼠的组织器官清除病原微生物的能力显著增强。FadR能够结合精氨酸脱亚胺酶(arginine deiminase, arcA)的启动子区域，FadR磷酸化增强了其与adi启动子的结合能力，提高了ADI蛋白的表达水平，加速了精氨酸向氨的转化过程，从而显著提高了SS2的耐酸性和毒力，削弱了受感染小鼠的组织器官清除病原微生物的能力^[75]。

LacI是一种细菌转录因子，通常用于人工将蛋白质招募到真核基因组上^[76]。近年来，许多研究表明LacI家族转录调控因子控制着细菌的多种代谢过程，如碳代谢、核苷酸合成和氨基酸分解等^[77-79]，并且可以调控细菌病原的毒力，碳代谢物蛋白激活因子A (carbon catabolite protein A, CcpA)是研究最为深入的LacI家族转录因子^[80-81]。除CcpA外，革兰氏阳性菌中也含有许多LacI型转录因子家族的其他成员，目前对这些成员的研究尚不够深入。LacI家族转录因子Rv3575c在胆固醇作为唯一碳源存在的情况下抑制M. tuberculosis的生长；LacI家族转录因子NCgl2689基因编码了参与谷氨酸菌L-半胱氨酸生物合成的NCgl2688基因的正调节因子，在谷氨酸棒杆菌(Corynebacterium glutamicum)的反向转硫途径中将半胱氨酸转化为L-半胱氨酸的过程中发挥了重要作用^[82]；RhaR是一种新型的LacI家族转录调节因子，它参与调节鼠李糖和含鼠李糖低聚糖的摄取和分解代谢相关基因的表达^[83]。在SS2中LacI的STK磷酸化位点为Thr-29，STK对LacI的磷酸化修饰阻止了其与靶启动子区域的结合^[84]。

2.6 孤儿调控因子CovR

二元转导系统是细菌中普遍存在的一种跨膜信号转导系统，CovS/CovR是链球菌中经典的二元转导系统^[85]。在酿脓链球菌(Streptococcus pyogenes)中CovS/CovR对透明质酸荚膜的产生起着负调控作用^[86-87]；在无乳链球菌(Streptococcus agalactiae)中CovS/CovR调节包括毒力因子在内的全基因组6%的基因表达^[88-89]；在S. suis中CovR是一个孤儿调控因子，无同源的组氨酸激酶编码基因(CovS)^[90]。在SS2中CovR的STK磷酸化位点为Thr-45、Thr-148、Thr-150、Thr-159、Thr-168、Thr-194、Thr-219、Ser-40、Ser-172、Ser-215、Lyr-225^[91-93]。遗憾的是，在鉴定出CovR的磷酸化位点后，学者并未进一步开展相关研究。

2.7 翻译延伸因子P

细菌延伸因子P (elongation factor P, EF-P)于20世纪70年代首次在大肠埃希氏菌中被鉴定，它与真核起始因子5A (eukaryotic initiation factor 5A, eIF 5A)具有同源性^[94]，其功能是增强含多聚脯氨酸蛋白的翻译^[95]。在细菌合成含有连续脯氨酸残基的蛋白质过程中，核糖体会发生停滞，需要EF-P的协助才能继续翻译。EF-P的翻译后修饰对于拯救核糖体停滞至关重要，在E. coli中EF-P通过β-赖氨酸化提高自身活性，促进含脯氨酸蛋白质的翻译效率；在S. aureus中EF-P能够发生鼠李糖基化，从而增强对抗生素的耐药性；在B. subtilis中EF-P发生5-氨基戊酰化并参与细菌蜂群运动的调控已被证实^[96-98]。在SS2中EF-P的磷酸化位点为Ser-148和Thr-176，EF-P磷酸化的加剧会导致SS2中丝氨酸蛋白酶的产量增加，从而增强细菌血脑屏障穿透力^[26]。

2.8 未定义蛋白OsrP

在许多细菌中超过1/3的蛋白质无任何注释功能，解析这些蛋白质的功能有助于更深入地了解细菌的生命活动和致病机制。OsrP是一个功能未知的蛋白，其缺失会导致SS2链长显著缩短，几乎无法形成链状结构，且毒力明显降低，显著弱于野生株；对人脑微血管内皮细胞(human brain microvascular endothelial cells, HBMEC)的黏附能力显著减弱，并且抵抗吞噬细胞吞噬的能力也减弱。细菌只能耐受一定程度的ROS，为了避免ROS水平失衡造成的细胞毒性，细菌已演化出多种对抗氧化应激的机制。在SS2中OsrP的磷酸化位点为Thr-48，OsrP的磷酸化修饰对SS2的抗氧化能力至关重要，缺失OsrP (或抑制其磷酸化)的SS2表现出抗氧化应激能力减弱^[99]。

3 STK系统在猪链球菌及其他经典细菌模型中的保守性与特异性

收起

尽管本文系统综述了SS2中STK的磷酸化底物及其功能，但STK/STP系统作为一种真核样信号转导机制，在多种细菌中广泛存在，并在不同病原菌中展现出结构和功能上的保守性与特异性(图2)。以下结合现有研究，对SS2 STK系统与其他重要病原菌中的同源系统进行简要比较，以期为理解该系统的进化意义和功能多样性提供线索。

3.1 不同血清型猪链球菌的STK

SS2和猪链球菌9型(Streptococcus suis serotype 9, SS9)是中国病猪中最常见的血清型。在SS9中STP仅存在于致病株中，说明STP参与了SS9的致病过程^[100]。目前，STK在S. suis中的研究主要集中于血清型2型，其他血清型中相关报道较少。这可能是由于SS2致病性强、研究集中度高所致。然而，基于SS2中STK在细胞分裂、荚膜合成、应激反应等方面的重要调控作用，合理推测STK系统在其他血清型中可能同样扮演关键角色。未来研究可借助基因组比对、保守结构域分析等手段，预测并验证STK在其他血清型中的底物与功能异同，这将有助于理解S. suis种内致病性差异的调控基础。

3.2 与链球菌属内其他病原菌的比较

在S. pneumoniae中STK/STP系统影响多组重要基因的转录，包括细胞壁代谢、DNA修复、铁摄取及氧化应激反应等功能^[101]。其中GlmM是本文提到的SS2的STK底物之一，它也是S. pneumoniae中第一个被发现的STK底物^[102]；在化脓链球菌(group A Streptococcus, GAS)中，STK/STP通过具有半胱氨酸和组氨酸依赖氨基水解酶(cysteine, histidine-dependent amidohydrolases/peptidases, CHAP)结构域，且具有功能活性细胞壁水解酶活性的分泌蛋白，调控细胞分裂、生长和毒力^[103]。CovR在SS2之前就已经被发现作为GAS的STK底物^[104]，磷酸化位点为Thr-65。通过点突变将Thr-65变为Glu持续激活其磷酸化后毒力增强^[105]。这一点提示CovR作为STK底物在链球菌属中可能具有保守的调控角色；在GBS中STK/STP的突变对细菌的生长分裂和毒力表现出多效性作用^[106]。琥珀酸合成酶、反应调节因子CovR和锰依赖性无机焦磷酸酶(PpaC)是GBS中已经被确认的STK底物蛋白，参与了碳水化合物代谢、ATP水解、氨基酸和核苷酸合成等过程^[107-109]。STK同样磷酸化GBS细胞分裂相关蛋白，比如DivIVA和FtsZ^[110-111]。大多数原核生物eSTK/STP是单次跨膜蛋白，主要由N端的激酶结构域、跨膜区和C端若干个青霉素结合蛋白和丝/苏氨酸激酶相关结构域(penicillin-binding protein and Ser/Thr kinase-associated domains, PASTA)组成^[112]。由于链球菌属eSTK/STP结构保守，磷酸化底物具有较多重合，因此STK在链球菌属内功能具有一定的相关性。

3.3 与其他经典细菌模型中STK系统的比较

与其他细菌相比，在链球菌属内STK/STP系统功能相对保守，而跨越种属后，STK/STP系统则表现出进化上的多样性。在S. aureus中PknB/STK的Ser/Thr磷酸化和STP的去磷酸化在细胞壁代谢、糖酵解、柠檬酸循环、嘌呤、嘧啶合成和翻译等中枢代谢过程中起着重要作用^[113]，其底物与链球菌属有部分重叠(如细胞壁合成、抗生素耐药等相关蛋白^[114])，但更多体现出物种特异性^[115]；在B. subtilis中STK (PrkC)与磷酸酶(PrpC)参与芽孢形成、细胞分裂及环境适应^[116]。PrkC可通过磷酸化底物如EF-Tu、RNA聚合酶等调控翻译与转录，体现出在细菌生理过程中的基础调控功能^[117]。与SS2相比，B. subtilis中STK更多与生长代谢、分化相关，而非直接调控细菌毒力，反映出STK系统在致病菌与非致病菌中的功能差异^[118-119]；在M. tuberculosis中STK系统(如PknA、PknB)十分复杂，参与细胞壁合成、代谢重组与持久感染^[120]。其底物数量远多于SS2，包括众多代谢酶、转录因子与分泌系统蛋白。然而，M. tuberculosis的PknB在协调细胞生长和分裂过程中的形态发生方面，功能与S. pneumoniae的STK/STP相似^[121]。在2个无关物种中真核生物型STK在控制细胞分裂的机制中存在，这又表明了STK/STP系统在细菌中的普遍性和重要性。

4 总结与展望

收起

细菌蛋白质磷酸化修饰，特别是由其真核样丝氨酸/苏氨酸激酶(STK)介导的磷酸化网络，在SS2的生理调控和毒力表达中扮演着核心角色，这种关键作用使STK及其底物成为具有吸引力的药物靶标。基于团队前期研究，本课题组在SS2中发现了一系列尚未被报道的STK激酶潜在底物蛋白，通过体外磷酸化实验与体内功能验证相结合的策略，证实了SS2自身的翻译延伸因子P是STK特异性磷酸化底物蛋白，并在S. suis破坏血脑屏障及致病过程中发挥重要作用^[26]。未来，团队将在此基础上继续拓宽SS2中STK调节网络的边界，为全面揭示SS2的致病机理提供依据。

目前，通过对SS2 STK磷酸化底物的研究已经帮助人们对SS2致病机制有了更为深入的了解和论证，但仍有许多STK底物蛋白未被提及，特别是未定义蛋白。随着生物信息学的发展，人们可以利用更多元、便捷的方式对未定义蛋白进行初步定义，未来可以借助人工智能和深度学习方法，大规模挖掘这些未知蛋白的潜在结构与功能。值得注意的是，关于本文提及SS2中的如BglF、MapZ、LacI、CovR和OsrP蛋白STK磷酸化的功能，目前报道仍较少，仅有早期的学位论文为理论支撑。对于本文提到的蛋白LacI和CovR等，依然保留着继续探索的空间，值得更加深入地研究。

基金

收起

国家自然科学基金(32473027)
国家自然科学基金(32172850)
国家生猪技术创新中心项目(NCTIP-XD/C17)
重庆现代农业产业技术体系(CQMAITS202512)
西南大学研究生科研创新项目(SWUB25087)

参考文献

收起

文献

收起

参考文献引证文献

排序方式：

[1]

, Yi

, Yu

, Wang

, Ma

, Lin

, Fan

. Streptococcus suis serotype 2 biofilms inhibit the formation of neutrophil extracellular traps[J]. Frontiers in Cellular and Infection Microbiology, 2017, 7: 86.

[2]

项维, 何伊妍, 何斌, 陈石, 李碧波, 吴利军, 雷连成, 张付贤. 1株猪源ST25型猪链球菌血清2型的分离鉴定及生物学特性研究[J]. 中国畜牧兽医, 2025, 52(12): 5979-5992.

Xiang

, He

, Chen

, Li

, Wu

, Lei

, Zhang

. Isolation, identification and biological characteristics of a strain of porcine ST25 Streptococcus suis serotype 2[J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(12): 5979-5992 (in Chinese).

[3]

Gottschalk

, Xu

, Calzas

, Segura

. Streptococcus suis: a new emerging or an old neglected zoonotic pathogen[J]. Future Microbiology, 2010, 5(3): 371-391.

[4]

Kerdsin

, Dejsirilert

, Puangpatra

, Sripakdee

, Chumla

, Boonkerd

, Polwichai

, Tanimura

, Takeuchi

, Nakayama

, Nakamura

, Akeda

, Gottschalk

, Sawanpanyalert

, Oishi

. Genotypic profile of Streptococcus suis serotype 2 and clinical features of infection in humans, Thailand[J]. Emerging Infectious Diseases, 2011, 17(5): 835-842.

[5]

Haas

, Grenier

. Understanding the virulence of Streptococcus suis: a veterinary, medical, and economic challenge[J]. Médecine et Maladies Infectieuses, 2018, 48(3): 159-166.

[6]

魏玉杰, 杨达汉, 于学武. 猪链球菌毒力因子研究新进展[J]. 中国人兽共患病学报, 2025, 41(6): 648-652.

Wei

, Yang

, Yu

. New research progress in virulence factors of Streptococcus suis [J]. Chinese Journal of Zoonoses, 2025, 41(6): 648-652 (in Chinese).

[7]

胡云皓, 佟仁冬, 辛凌翔, 刘燕, 王豪杰, 郝力力, 朱良全. 猪链球菌2型的主要毒力因子与先天性免疫逃逸机制[J]. 中国兽医杂志, 2024, 60(10): 98-105.

, Tong

, Xin

, Liu

, Wang

, Hao

, Zhu

. Major virulence factors and innate immune evasion mechanisms of Streptococcus suis serotype 2[J]. Chinese Journal of Veterinary Medicine, 2024, 60(10): 98-105 (in Chinese).

[8]

董晨晖, 金美君, 李建, 岳怀宁, 刘燕, 王豪杰, 胡云皓, 朱良全. 猪链球菌2型关键毒力因子及诱发疾病机制的研究进展[J]. 微生物学通报, 2025, 52(1): 127-136.

Dong

, Jin

, Li

, Yue

, Liu

, Wang

, Hu

, Zhu

. Research progress in critical virulence factors of Streptococcus suis serotype 2 and its disease-inducing mechanisms[J]. Microbiology China, 2025, 52(1): 127-136 (in Chinese).

[9]

Segura

, Fittipaldi

, Calzas

, Gottschalk

. Critical Streptococcus suis virulence factors: are they all really critical[J]. Trends in Microbiology, 2017, 25(7): 585-599.

[10]

Grangeasse

, Cozzone

, Deutscher

, Mijakovic

. Tyrosine phosphorylation: an emerging regulatory device of bacterial physiology[J]. Trends in Biochemical Sciences, 2007, 32(2): 86-94.

[11]

Mijakovic

, Grangeasse

, Turgay

. Exploring the diversity of protein modifications: special bacterial phosphorylation systems[J]. FEMS Microbiology Reviews, 2016, 40(3): 398-417.

[12]

Manai

, Cozzone

. Analysis of the protein-kinase activity of Escherichia coli cells[J]. Biochemical and Biophysical Research Communications, 1979, 91(3): 819-826.

[13]

Wang

, Koshland

. Evidence for protein kinase activities in the prokaryote Salmonella typhimurium [J]. Journal of Biological Chemistry, 1978, 253(21): 7605-7608.

[14]

, Shan

. Bacterial phosphoproteomic analysis reveals the correlation between protein phosphorylation and bacterial pathogenicity[J]. Genomics, Proteomics & Bioinformatics, 2011, 9(4/5): 119-127.

[15]

Frando

, Grundner

. More than two components: complexities in bacterial phosphosignaling[J]. mSystems, 2024, 9(5): e00289-24.

[16]

Cohen

. The origins of protein phosphorylation[J]. Nature Cell Biology, 2002, 4(5): E127-E130.

[17]

Ohlsen

, Donat

. The impact of serine/threonine phosphorylation in Staphylococcus aureus [J]. International Journal of Medical Microbiology, 2010, 300(2/3): 137-141.

[18]

Nagarajan

, Lenoir

, Grangeasse

. Recent advances in bacterial signaling by serine/threonine protein kinases[J]. Trends in Microbiology, 2022, 30(6): 553-566.

[19]

Janczarek

, Vinardell

, Lipa

, Karaś

. Hanks-type serine/threonine protein kinases and phosphatases in bacteria: roles in signaling and adaptation to various environments[J]. International Journal of Molecular Sciences, 2018, 19(10): 2872.

[20]

Zhu

, Zhou

, Ni

, Yu

, Mao

, Hu

, Wang

, Zhang

, Wen

, Li

, Wang

, Yu

, Lv

, Guo

, Lu

, He

. Contribution of eukaryotic-type serine/threonine kinase to stress response and virulence of Streptococcus suis [J]. PLoS One, 2014, 9(3): e91971.

[21]

Zhang

, Sun

, Tan

, Dong

, Liu

, Gao

, Li

, Xu

, Zhou

. The eukaryote-like serine/threonine kinase STK regulates the growth and metabolism of zoonotic Streptococcus suis [J]. Frontiers in Cellular and Infection Microbiology, 2017, 7: 66.

[22]

, Li

, Hu

, Yao

, Li

, Huang

, Zhou

. Inhibitors targeting the autophosphorylation of serine/threonine kinase of Streptococcus suis show potent antimicrobial activity[J]. Frontiers in Microbiology, 2022, 13: 990091.

[23]

, Yao

, Liao

, Zhang

, Li

, Jiang

, Tan

, Li

, Draheim

, Huang

, Zhou

. Comparative phenotypic, proteomic, and phosphoproteomic analysis reveals different roles of serine/threonine phosphatase and kinase in the growth, cell division, and pathogenicity of Streptococcus suis [J]. Microorganisms, 2021, 9(12): 2442.

[24]

杜骁杰, 王玲, 郑峰, 李敏, 王晶, 胡丹, 李先富, 王长军, 潘秀珍. 猪链球菌真核样丝氨酸/苏氨酸激酶stk基因敲除株的构建[J]. 中国人兽共患病学报, 2013, 29(12): 1162-1167.

, Wang

, Zheng

, Li

, Wang

, Hu

, Li

, Wang

, Pan

. Development of the eukaryotic-like Ser/Thr kinase stk gene knock-out mutant of Streptococcus suis [J]. Chinese Journal of Zoonoses, 2013, 29(12): 1162-1167 (in Chinese).

[25]

杜骁杰. 猪链球菌真核样丝氨酸/苏氨酸激酶stk基因功能的实验研究[D]. 南京: 南京师范大学, 2014.

. Experimental study on the function of the eukaryotic-like serine/threonine kinase stk gene in Streptococcus suis [D]. Nanjing: Nanjing Normal University, 2014 (in Chinese).

[26]

Yin

, Tian

, Zhou

, Lang

, Li

, Peng

, Li

, Fang

. Phosphorylation of EF-P aggravates Streptococcus suis-induced blood-brain barrier damage by enhancing serine protease production[J]. Veterinary Research, 2025, 56: 215.

[27]

Milewski

, Gabriel

, Olchowy

. Enzymes of UDP-GlcNAc biosynthesis in yeast[J]. Yeast, 2006, 23(1): 1-14.

[28]

Agarwal

, Bhaskar

, Singha

, Mukhopadhyay

, Pahuja

, Singh

, Chaturvedi

, Agarwal

, Dwivedi

, Nandicoori

. Depletion of essential mycobacterial gene glmM reduces pathogen survival and induces host-protective immune responses against tuberculosis[J]. Communications Biology, 2024, 7: 949.

[29]

Glanzmann

, Gustafson

, Komatsuzawa

, Ohta

, Berger-Bächi

. glmM operon and methicillin-resistant glmM suppressor mutants in Staphylococcus aureus [J]. Antimicrobial Agents and Chemotherapy, 1999, 43(2): 240-245.

[30]

Tosi

, Hoshiga

, Millership

, Singh

, Eldrid

, Patin

, Mengin-Lecreulx

, Thalassinos

, Freemont

, Gründling

. Inhibition of the Staphylococcus aureus c-di-AMP cyclase DacA by direct interaction with the phosphoglucosamine mutase GlmM[J]. PLoS Pathogens, 2019, 15(1): e1007537.

[31]

Pathania

, Tosi

, Millership

, Hoshiga

, Morgan

RML

, Freemont

, Gründling

. Structural basis for the inhibition of the Bacillus subtilis c-di-AMP cyclase CdaA by the phosphoglucomutase GlmM[J]. Journal of Biological Chemistry, 2021, 297(5): 101317.

[32]

, Yin

, Meng

, Ma

, Lin

, Fan

. The phosphorylation of phosphoglucosamine mutase GlmM by Ser/Thr kinase STK mediates cell wall synthesis and virulence in Streptococcus suis serotype 2[J]. Veterinary Microbiology, 2021, 258: 109102.

[33]

李唯一. STK/STP的磷酸化影响猪链球菌2型生物学特性及毒力的机制[D]. 南京: 南京农业大学, 2020.

. The mechanism of STK/STP phosphorylation affecting biological characteristics and virulence of Streptococcus suis serotype 2[D]. Nanjing: Nanjing Agricultural University, 2020 (in Chinese).

[34]

Schnetz

, Rak

. Regulation of the Bgl operon of Escherichia coli by transcriptional antitermination[J]. The EMBO Journal, 1988, 7(10): 3271-3277.

[35]

Amster-Choder

, Houman

, Wright

. Protein phosphorylation regulates transcription of the β-glucoside utilization operon in E. coli [J]. Cell, 1989, 58(5): 847-855.

[36]

Lopian

, Nussbaum-Shochat

, O’Day-Kerstein

, Wright

, Amster-Choder

. The BglF sensor recruits the BglG transcription regulator to the membrane and releases it on stimulation[J]. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(12): 7099-7104.

[37]

Deutscher

, Aké

FMD

, Derkaoui

, Zébré

, Cao

, Bouraoui

, Kentache

, Mokhtari

, Milohanic

, Joyet

. The bacterial phosphoenolpyruvate: carbohydrate phosphotransferase system: regulation by protein phosphorylation and phosphorylation-dependent protein-protein interactions[J]. Microbiology and Molecular Biology Reviews, 2014, 78(2): 231-256.

[38]

Jankute

, Cox

JAG

, Harrison

, Besra

. Assembly of the mycobacterial cell wall[J]. Annual Review of Microbiology, 2015, 69: 405-423.

[39]

Gilmore

, Cava

. Bacterial peptidoglycan recycling[J]. Trends in Microbiology, 2025, 33(3): 340-353.

[40]

Trouve

, Zapun

, Bellard

, Juillot

, Pelletier

, Freton

, Baudoin

, Carballido-Lopez

, Campo

, Wong

, Grangeasse

, Morlot

. DivIVA controls the dynamics of septum splitting and cell elongation in Streptococcus pneumoniae [J]. mBio, 2024, 15(10): e01311-24.

[41]

, Xu

, Shi

, Chu

, Jiang

, Li

, Luo

. Localization characteristics of cell wall synthesis protein Wag31 and penicillin binding protein C in Clavibacter michiganensis [J]. The Cell Surface, 2025, 14: 100151.

[42]

Zamakhaeva

, Chaton

, Rush

, Ajay Castro

, Kenner

, Yarawsky

, Herr

, van Sorge

, Dorfmueller

, Frolenkov

, Korotkov

, Korotkova

. Modification of cell wall polysaccharide guides cell division in Streptococcus mutans [J]. Nature Chemical Biology, 2021, 17(8): 878-887.

[43]

Eswaramoorthy

, Winter

, Wawrzusin

, York

, Shroff

, Ramamurthi

. Asymmetric division and differential gene expression during a bacterial developmental program requires DivIVA[J]. PLoS Genetics, 2014, 10(8): e1004526.

[44]

Meniche

, Otten

, Siegrist

, Baer

, Murphy

, Bertozzi

, Sassetti

. Subpolar addition of new cell wall is directed by DivIVA in mycobacteria[J]. Proceedings of the National Academy of Sciences of the United States of America, 2014, 111(31): E3243-E3251.

[45]

Fleurie

, Manuse

, Zhao

, Campo

, Cluzel

, Lavergne

, Freton

, Combet

, Guiral

, Soufi

, Macek

, Kuru

, VanNieuwenhze

, Brun

, Di Guilmi

, Claverys

, Galinier

, Grangeasse

. Interplay of the serine/threonine-kinase StkP and the paralogs DivIVA and GpsB in pneumococcal cell elongation and division[J]. PLoS Genetics, 2014, 10(4): e1004275.

[46]

Thomaides

, Freeman

, El Karoui

, Errington

. Division site selection protein DivIVA of Bacillus subtilis has a second distinct function in chromosome segregation during sporulation[J]. Genes & Development, 2001, 15(13): 1662-1673.

[47]

Ortiz

, Natale

, Cueto

, Vicente

. The keepers of the ring: regulators of FtsZ assembly[J]. FEMS Microbiology Reviews, 2016, 40(1): 57-67.

[48]

Wang

, Zhang

, Du

, Zhou

, Chen

. How do MinC-D copolymers act on Z-ring localization regulation a new model of Bacillus subtilis Min system[J]. Frontiers in Microbiology, 2022, 13: 841171.

[49]

Liu

, Basu

, Miller

, McMullen

. Stress response and adaptation of Listeria monocytogenes 08-5923 exposed to a sublethal dose of carnocyclin A[J]. Applied and Environmental Microbiology, 2014, 80(13): 3835-3841.

[50]

Matusiak

, Strzałka

, Wadach

, Gongerowska-Jac

, Szwajczak

, Szydłowska-Helbrych

, Kepplinger

, Pióro

, Jakimowicz

. The interplay between the polar growth determinant DivIVA, the segregation protein ParA, and their novel interaction partner PapM controls the Mycobacterium smegmatis cell cycle by modulation of DivIVA subcellular distribution[J]. Microbiology Spectrum, 2023, 11(6): e01752-23.

[51]

Jiang

, Li

, Zhang

, Li

, Hu

, Li

, Zou

, Hu

, Huang

, Zhou

. DivIVA interacts with the cell wall hydrolase MltG to regulate peptidoglycan synthesis in Streptococcus suis [J]. Microbiology Spectrum, 2023, 11(3): e04750-22.

[52]

, Fan

, Li

, Wu

, Hou

, Hu

, Zheng

, Zhu

, Wang

, Cao

, Shao

, Pan

. Streptococcus suis DivIVA protein is a substrate of Ser/Thr kinase STK and involved in cell division regulation[J]. Frontiers in Cellular and Infection Microbiology, 2018, 8: 85.

[53]

Liu

, Ye

, Fu

, Yue

, Li

, Fang

. Stk and Stp1 participate in Streptococcus suis serotype 2 pathogenesis by regulating capsule thickness and translocation of certain virulence factors[J]. Microbial Pathogenesis, 2021, 152: 104607.

[54]

Santos-Beneit

, Roberts

, Cantlay

, McCormick

, Errington

. A mechanism for FtsZ-independent proliferation in Streptomyces [J]. Nature Communications, 2017, 8: 1378.

[55]

Barrows

, Goley

. FtsZ dynamics in bacterial division: what, how, and why[J]. Current Opinion in Cell Biology, 2021, 68: 163-172.

[56]

张春艳. 丝氨酸/苏氨酸激酶STK调控猪链球菌生长和致病性的分子机制研究[D]. 武汉: 华中农业大学, 2017.

Zhang

. Regulaton of serine/threonine kinase on the growth and pathogenesis of Streptococcus suis [D]. Wuhan: Huazhong Agricultural University, 2017 (in Chinese).

[57]

, Shao

, Xu

, Su

, Sun

, Wei

. MapZ forms a stable ring structure that acts as a nanotrack for FtsZ treadmilling in Streptococcus mutans [J]. ACS Nano, 2018, 12(6): 6137-6146.

[58]

Fleurie

, Lesterlin

, Manuse

, Zhao

, Cluzel

, Lavergne

, Franz-Wachtel

, Macek

, Combet

, Kuru

, VanNieuwenhze

, Brun

, Sherratt

, Grangeasse

. MapZ marks the division sites and positions FtsZ rings in Streptococcus pneumoniae [J]. Nature, 2014, 516(7530): 259-262.

[59]

廖峡. MapZ及其磷酸化调控猪链球菌细胞分裂的分子机制研究[D]. 武汉: 华中农业大学, 2021.

Liao

. Regulation of MapZ and its phosphorylation on the cell division of Streptococcus suis [D]. Wuhan: Huazhong Agricultural University, 2021 (in Chinese).

[60]

Dolbec

, Lehoux

, Okura

, Takamatsu

, Gottschalk

, Segura

. Streptococcus suis surface-antigen recognition by antibodies and bacterial elimination is influenced by capsular polysaccharide structure[J]. Frontiers in Cellular and Infection Microbiology, 2023, 13: 1228496.

[61]

Tang

, Guo

, Chen

, Xu

, Ran

, Wang

, Ma

, Lin

, Fan

. A link between STK signalling and capsular polysaccharide synthesis in Streptococcus suis [J]. Nature Communications, 2023, 14: 2480.

[62]

唐金升. 磷酸化依赖的CcpS和CpsC调控猪链球菌2型荚膜合成及毒力的机制[D]. 南京: 南京农业大学, 2023.

Tang

. The mechanism of phosphorylation-dependent CcpS and CpsC modulating bacterial capsule biosynthesis and virulence in Streptococcus suis serotype 2[D]. Nanjing: Nanjing Agricultural University, 2023 (in Chinese).

[63]

林苗, 倪华, 汪雨荷, 郑峰, 唐成亮, 潘秀珍. 血清2型猪链球菌酪氨酸激酶Cps2C突变株致病力分析[J]. 中国人兽共患病学报, 2024, 40(11): 1009-1017.

Lin

, Ni

, Wang

, Zheng

, Tang

, Pan

. Pathogenicity analysis of a tyrosine kinase Cps2C mutant strain of Streptococcus suis serotype 2[J]. Chinese Journal of Zoonoses, 2024, 40(11): 1009-1017 (in Chinese).

[64]

Bender

, Yother

. CpsB is a modulator of capsule-associated tyrosine kinase activity in Streptococcus pneumoniae [J]. Journal of Biological Chemistry, 2001, 276(51): 47966-47974.

[65]

Zheng

, Lin

, Fang

, Wang

, Liu

, Tang

, Wang

, Shao

, Ni

, Pan

. Tyrosine kinase Cps2C regulates the synthesis of capsular polysaccharides and plays a role in the virulence of Streptococcus suis serotype 2[J]. Virulence, 2025, 16: 2562648.

[66]

张会芳. 2型猪链球菌05ZYH33酪氨酸蛋白激酶磷酸化的初步研究[D]. 南京: 南京师范大学, 2020.

Zhang

. Preliminary study on the phosphorylation of tyrosine protein kinase by Streptococcus suis serotype 05ZYH33[D]. Nanjing: Nanjing Normal University, 2020 (in Chinese).

[67]

Baumgart

, Lee

, Salamov

, Dilworth

, Na

, Mingay

, Blow

, Zhang

, Yoshinaga

, Daum

, O’Malley

. Persistence and plasticity in bacterial gene regulation[J]. Nature Methods, 2021, 18(12): 1499-1505.

[68]

Liu

, Wang

, Su

, Lu

. Progress on the GntR family transcription regulators in bacteria[J]. Hereditas, 2021, 43(1): 66-73.

[69]

Suvorova

, Korostelev

, Gelfand

. GntR family of bacterial transcription factors and their DNA binding motifs: structure, positioning and co-evolution[J]. PLoS One, 2015, 10(7): e0132618.

[70]

Niu

, Meng

, Liu

, Ma

, Lin

, Zhou

, Fan

. Phosphorylation of GntR reduces Streptococcus suis oxidative stress resistance and virulence by inhibiting NADH oxidase transcription[J]. PLoS Pathogens, 2023, 19(3): e1011227.

[71]

Jiang

, Wang

, Xu

, Mu

, Hong

, He

, Jiang

, Qiu

. DipR, a GntR/FadR-family transcriptional repressor: regulatory mechanism and widespread distribution of the dip cluster for dipicolinic acid catabolism in bacteria[J]. Nucleic Acids Research, 2024, 52(18): 10951-10964.

[72]

Shi

, Kovacikova

, Lin

, Taylor

, Skorupski

, Kull

. The 40-residue insertion in Vibrio cholerae FadR facilitates binding of an additional fatty acyl-CoA ligand[J]. Nature Communications, 2015, 6: 6032.

[73]

Kim

, Yoo

, Kim

, Sung

, Lee

, Park

, Kim

. Rewiring FadR regulon for the selective production of ω-hydroxy palmitic acid from glucose in Escherichia coli [J]. Metabolic Engineering, 2018, 47: 414-422.

[74]

Yeo

, Park

, Lee

. Structural basis of operator sites recognition and effector binding in the TetR family transcription regulator FadR[J]. Nucleic Acids Research, 2017, 45(7): 4244-4254.

[75]

, Ma

, Lin

, Pan

, Zhou

, Tang

, Fan

. STK-mediated FadR phosphorylation regulates the acid resistance and virulence of Streptococcus suis [J]. PLoS Pathogens, 2025, 21(9): e1013534.

[76]

, Kodner

, Bai

. Enhancement of LacI binding in vivo [J]. Nucleic Acids Research, 2019, 47(18): 9609-9618.

[77]

Weickert

, Adhya

. A family of bacterial regulators homologous to Gal and Lac repressors[J]. Journal of Biological Chemistry, 1992, 267(22): 15869-15874.

[78]

Swint-Kruse

, Matthews

. Allostery in the LacI/GalR family: variations on a theme[J]. Current Opinion in Microbiology, 2009, 12(2): 129-137.

[79]

Nguyen

, Saier

. Phylogenetic, structural and functional analyses of the LacI-GalR family of bacterial transcription factors[J]. FEBS Letters, 1995, 377(2): 98-102.

[80]

, Sun

, Cho

, Yelavarthi

, Sohn

, He

, Schneewind

, Bae

. CcpA mediates proline auxotrophy and is required for Staphylococcus aureus pathogenesis[J]. Journal of Bacteriology, 2010, 192(15): 3883-3892.

[81]

Tchawa Yimga

, Leatham

, Allen

, Laux

, Conway

, Cohen

. Role of gluconeogenesis and the tricarboxylic acid cycle in the virulence of Salmonella enterica serovar typhimurium in BALB/c mice[J]. Infection and Immunity, 2006, 74(2): 1130-1140.

[82]

Chen

, Zhang

, Xu

, Li

, Bai

, Li

, Cai

, Wei

, Wang

, Su

, Xu

. The LacI-type transcriptional activator NCgl2689 directly regulates an operon involved in L-cysteine synthesis by the reverse transsulfuration pathway in Corynebacterium glutamicum [J]. Journal of Agricultural and Food Chemistry, 2025, 73(35): 21999-22007.

[83]

Yang

, Luan

, Wang

, Zhang

, Liu

, Niu

. Characterizing and engineering rhamnose-inducible regulatory systems for dynamic control of metabolic pathways in Streptomyces [J]. ACS Synthetic Biology, 2024, 13(10): 3461-3470.

[84]

刘峻池. 磷酸化修饰对猪链球菌2型LacI家族转录因子调控功能的影响[D]. 南京: 南京农业大学, 2021.

Liu

. The influence of phosphorylation modification on the regulatory function of LacI family transcription factor in Streptococcus suis serotype 2[D]. Nanjing: Nanjing Agricultural University, 2021 (in Chinese).

[85]

Yeo

, Dyzenhaus

, Torres

, Brinsmade

, Bae

. Regulation of bacterial two-component systems by cardiolipin[J]. Infection and Immunity, 2023, 91(4): e00046-23.

[86]

Heath

, DiRita

, Barg

, Engleberg

. A two-component regulatory system, CsrR-CsrS, represses expression of three Streptococcus pyogenes virulence factors, hyaluronic acid capsule, streptolysin S, and pyrogenic exotoxin B[J]. Infection and Immunity, 1999, 67(10): 5298-5305.

[87]

Federle

, McIver

, Scott

. A response regulator that represses transcription of several virulence operons in the group a Streptococcus [J]. Journal of Bacteriology, 1999, 181(12): 3649-3657.

[88]

Coppolino

, de Gaetano

, Claverie

, Sismeiro

, Varet

, Legendre

, Pellegrini

, Berbiglia

, Tavella

, Lentini

, Famà

, Barbieri

, Pietrocola

, Teti

, Firon

, Beninati

. The SaeRS two-component system regulates virulence gene expression in group B Streptococcus during invasive infection[J]. mBio, 2024, 15(9): e01975-24.

[89]

Jiang

, Cieslewicz

, Kasper

, Wessels

. Regulation of virulence by a two-component system in group B Streptococcus [J]. Journal of Bacteriology, 2005, 187(3): 1105-1113.

[90]

Pan

, Ge

, Li

, Wu

, Wang

, Feng

, Yin

, Zheng

, Cheng

, Sun

, Ji

, Hu

, Shi

, Feng

, Hao

, Dong

, Hu

, Tang

. The orphan response regulator CovR: a globally negative modulator of virulence in Streptococcus suis serotype 2[J]. Journal of Bacteriology, 2009, 191(8): 2601-2612.

[91]

郭静静. 猪链球菌反应调节因子CovR靶基因的鉴定及其磷酸化调控系统Stk/Stp蛋白的原核表达[D]. 南京: 南京师范大学, 2013.

Guo

. Identification of CovR target genes in Streptococcus suis and prokaryotic expression of the phosphorylation regulatory system Stk/Stp proteins[D]. Nanjing: Nanjing Normal University, 2013 (in Chinese).

[92]

李先富, 郝喜娜, 韩明月, 王长军, 唐家琪, 潘秀珍. 猪链球菌反应调节因子CovR单克隆抗体的制备与鉴定[J]. 医学研究生学报, 2010(8): 809-812.

, Hao

, Han

, Wang

, Tang

, Pan

. Preparation and identification of monoclonal antibodies against CovR of Streptococcus suis serotype 2[J]. Journal of Medical Postgraduates, 2010(8): 809-812 (in Chinese).

[93]

郝喜娜, 史沛举, 葛俊超, 王晶, 王长军, 潘秀珍, 唐家琪. 猪链球菌2型中国强毒株CovR重组蛋白及其抗体的制备[J]. 中国人兽共患病学报, 2009, 25(4): 354-357.

Hao

, Shi

, Ge

, Wang

, Pan

, Tang

. Prokaryotic expression and polyclonal antibody preparation of response regulator CovR of Streptococcus suis serotype 2[J]. Chinese Journal of Zoonoses, 2009, 25(4): 354-357 (in Chinese).

[94]

Rossi

, Kuroshu

, Zanelli

, Valentini

. eIF5A and EF-P: two unique translation factors are now traveling the same road[J]. WIREs RNA, 2014, 5(2): 209-222.

[95]

Doerfel

, Wohlgemuth

, Kothe

, Peske

, Urlaub

, Rodnina

. EF-P is essential for rapid synthesis of proteins containing consecutive proline residues[J]. Science, 2013, 339(6115): 85-88.

[96]

Zou

, Roy

, Ibba

, Navarre

. Elongation factor P mediates a novel post-transcriptional regulatory pathway critical for bacterial virulence[J]. Virulence, 2011, 2(2): 147-151.

[97]

Ude

, Lassak

, Starosta

, Kraxenberger

, Wilson

, Jung

. Translation elongation factor EF-P alleviates ribosome stalling at polyproline stretches[J]. Science, 2013, 339(6115): 82-85.

[98]

Krafczyk

, Macošek

, Jagtap

PKA

, Gast

, Wunder

, Mitra

, Jha

, Rohr

, Hoffmann-Röder

, Jung

, Hennig

, Lassak

. Structural basis for EarP-mediated arginine glycosylation of translation elongation factor EF-P[J]. mBio, 2017, 8(5): e01412-17.

[99]

牛凯. GntR和OsrP磷酸化修饰调控猪链球菌2型抗氧化能力的机制[D]. 南京: 南京农业大学, 2023.

Niu

. The mechanism of GntR and OsrP phosphorylation modification in regulating the antioxidant capacity of Streptococcus suis type 2[D]. Nanjing: Nanjing Agricultural University, 2023 (in Chinese).

[100]

Zhu

, Huang

, Zhang

, Wu

, Lu

, Jia

, Wang

, Lu

. The novel virulence-related gene stp of Streptococcus suis serotype 9 strain contributes to a significant reduction in mouse mortality[J]. Microbial Pathogenesis, 2011, 51(6): 442-453.

[101]

Sasková

, Nováková

, Basler

, Branny

. Eukaryotic-type serine/threonine protein kinase StkP is a global regulator of gene expression in Streptococcus pneumoniae [J]. Journal of Bacteriology, 2007, 189(11): 4168-4179.

[102]

Nováková

, Sasková

, Pallová

, Janeček

, Novotná

, Ulrych

, Echenique

, Trombe

, Branny

. Characterization of a eukaryotic type serine/threonine protein kinase and protein phosphatase of Streptococcus pneumoniae and identification of kinase substrates[J]. The FEBS Journal, 2005, 272(5): 1243-1254.

[103]

Pancholi

, Boël

, Jin

. Streptococcus pyogenes Ser/Thr kinase-regulated cell wall hydrolase is a cell division plane-recognizing and chain-forming virulence factor[J]. Journal of Biological Chemistry, 2010, 285(40): 30861-30874.

[104]

Agarwal

, Agarwal

, Pancholi

. Role of serine/threonine phosphatase (SP-STP) in Streptococcus pyogenes physiology and virulence[J]. Journal of Biological Chemistry, 2011, 286(48): 41368-41380.

[105]

Horstmann

, Saldaña

, Sahasrabhojane

, Yao

, Su

, Thompson

, Koller

, Shelburne

. Dual-site phosphorylation of the control of virulence regulator impacts group a streptococcal global gene expression and pathogenesis[J]. PLoS Pathogens, 2014, 10(5): e1004088.

[106]

Rajagopal

, Clancy

, Rubens

. A eukaryotic type serine/threonine kinase and phosphatase in Streptococcus agalactiae reversibly phosphorylate an inorganic pyrophosphatase and affect growth, cell segregation, and virulence[J]. Journal of Biological Chemistry, 2003, 278(16): 14429-14441.

[107]

Shintani

, Uchiumi

, Yonezawa

, Salminen

, Baykov

, Lahti

, Hachimori

. Cloning and expression of a unique inorganic pyrophosphatase from Bacillus subtilis: evidence for a new family of enzymes[J]. FEBS Letters, 1998, 439(3): 263-266.

[108]

Rajagopal

, Vo

, Silvestroni

, Rubens

. Regulation of purine biosynthesis by a eukaryotic-type kinase in Streptococcus agalactiae [J]. Molecular Microbiology, 2005, 56(5): 1329-1346.

[109]

Rajagopal

, Vo

, Silvestroni

, Rubens

. Regulation of cytotoxin expression by converging eukaryotic-type and two-component signalling mechanisms in Streptococcus agalactiae [J]. Molecular Microbiology, 2006, 62(4): 941-957.

[110]

Silvestroni

, Jewell

, Lin

, Connelly

, Ivancic

, Tao

, Rajagopal

. Identification of serine/threonine kinase substrates in the human pathogen group B Streptococcus [J]. Journal of Proteome Research, 2009, 8(5): 2563-2574.

[111]

杜骁杰, 潘秀珍. 真核样丝氨酸/苏氨酸激酶在链球菌中的研究进展[J]. 中国病原生物学杂志, 2014, 9(3): 282-285.

, Pan

. Eukaryotic-like serine/threonine kinase in Streptococcus [J]. Journal of Pathogen Biology, 2014, 9(3): 282-285 (in Chinese).

[112]

O’Boyle

, Yeung

, Lu

, Katiyar

, Yaron-Barir

, Johnson

, Cantley

, Kannan

. An atlas of bacterial serine-threonine kinases reveals functional diversity and key distinctions from eukaryotic kinases[J]. Science Signaling, 2025, 18(885): eadt8686.

[113]

Chatterjee

, Poon

, Chatterjee

. Stp1 loss of function promotes β-lactam resistance in Staphylococcus aureus that is independent of classical genes[J]. Antimicrobial Agents and Chemotherapy, 2020, 64(6): e02222-19.

[114]

Huemer

, Mairpady Shambat

, Hertegonne

, Bergada-Pijuan

, Chang

, Pereira

, Gómez-Mejia

, Van Gestel

, Bär

, Vulin

, Pfammatter

, Stinear

, Monk

, Dworkin

, Zinkernagel

. Serine-threonine phosphoregulation by PknB and Stp contributes to quiescence and antibiotic tolerance in Staphylococcus aureus [J]. Science Signaling, 2023, 16(766): eabj8194.

[115]

Leiba

, Hartmann

, Cluzel

, Cohen-Gonsaud

, Delolme

, Bischoff

, Molle

. A novel mode of regulation of the Staphylococcus aureus catabolite control protein a (CcpA) mediated by Stk1 protein phosphorylation[J]. Journal of Biological Chemistry, 2012, 287(52): 43607-43619.

[116]

Squeglia

, Marchetti

, Ruggiero

, Lanzetta

, Marasco

, Dworkin

, Petoukhov

, Molinaro

, Berisio

, Silipo

. Chemical basis of peptidoglycan discrimination by PrkC, a key kinase involved in bacterial resuscitation from dormancy[J]. Journal of the American Chemical Society, 2011, 133(51): 20676-20679.

[117]

, Cui

, Zhang

, Shi

, Fang

, Dong

, Hu

. The functional network of PrkC and its interaction proteins in Bacillus subtilis spores[J]. Microorganisms, 2025, 13(4): 744.

[118]

Libby

, Goss

, Dworkin

. The eukaryotic-like Ser/Thr kinase PrkC regulates the essential WalRK two-component system in Bacillus subtilis [J]. PLoS Genetics, 2015, 11(6): e1005275.

[119]

Foulquier

, Pompeo

, Freton

, Cordier

, Grangeasse

, Galinier

. PrkC-mediated phosphorylation of overexpressed YvcK protein regulates PBP1 protein localization in Bacillus subtilis mreB mutant cells[J]. Journal of Biological Chemistry, 2014, 289(34): 23662-23669.

[120]

Walburger

, Koul

, Ferrari

, Nguyen

, Prescianotto-Baschong

, Huygen

, Klebl

, Thompson

, Bacher

, Pieters

. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages[J]. Science, 2004, 304(5678): 1800-1804.

[121]

Kang

, Abbott

, Park

, Dascher

, Cantley

, Husson

. The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape[J]. Genes & Development, 2005, 19(14): 1692-1704.

2026年第66卷第7期

PDF下载

139

引用本文

BibTeX

文章信息

doi: 10.13343/j.cnki.wsxb.20250786

接收时间：2025-10-20
首发时间：2026-07-06
出版时间：2026-07-04

补充材料

相关文章

文章信息

作者

出版历史

收稿日期：2025-10-20
录用日期：2026-02-13

基金

The National Natural Science Foundation of China(32473027)

国家自然科学基金(32473027)

国家自然科学基金(32172850)

The National Center of Technology Innovation for Pigs(NCTIP-XD/C17)

国家生猪技术创新中心项目(NCTIP-XD/C17)

The Chongqing Modern Agricultural Industry Technology System(CQMAITS202512)

重庆现代农业产业技术体系(CQMAITS202512)

The Southwest University Graduate Research Innovation Project(SWUB25087)

西南大学研究生科研创新项目(SWUB25087)

作者信息

^1.西南大学动物医学院，动物健康与动物性食品安全国际联合实验室，重庆

^2.国家生猪技术创新中心，重庆

通讯作者:

参考文献

分享链接

https://castjournals.cast.org.cn/joweb/wswxb/CN/10.13343/j.cnki.wsxb.20250786

分享至

全文二维码

扫描看全文

引用本文

BibTeX

本文的引用情况

2种不同金属材料的力学参数

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

关闭全屏

BibTeX
EndNote
RefWorks
TxT

SS2 strains	Substrate proteins	Phosphorylation sites	Biological characteristics	Effect on virulence of deficiency
SC19	STK (autophosphorylation)	Thr-167, Ser-175	Phosphorylated kinase, regulating downstream signal transduction	Decline
ZY05719	GlmM	Ser-101	Catalyses the synthesis of peptidoglycan precursors, maintaining cell wall integrity	Decline
ZY05719	BglF	Ser-462	PTS system components, regulating β-glucoside uptake and metabolism	Decline
05ZYH33	DivIVA	Ser-145, Thr-199, Thr-211	Regulating cell polarity and division, directing the localisation of cell wall hydrolases	Unknown
SC19	FtsZ	Thr-217, Thr-233, Thr-349, Thr-383	A key protein in cell division, forming Z-rings to direct spindle assembly	Unknown
SC19	MapZ	Thr-26, Thr-66	Localise cleavage sites, stabilise Z-rings, and regulate membrane contraction	Unknown
ZY05719	Ccps	Thr-4, Thr-7	Regulating the activity of tyrosine phosphatase CpsB, influencing capsular synthesis	Decline
05ZYH33	Cps2C	Unknown	Tyrosine kinase associated with capsular synthesis	Decline
ZY05719	GntR	Ser-41	Transcription factors regulating antioxidant stress-related genes (such as nox)	Decline
ZY05719	FadR	Thr-230	Transcription factors regulate the arginine deiminase (ADI) pathway, influencing acid tolerance	Decline
ZY05719	LacI	Thr-29	LacI family transcription factors, presumed to be involved in metabolic regulation	Unknown
05ZYH33	CovR	Thr-45, Thr-148, Thr-150, Thr-159, Thr-168, Thr-194, Thr-219, Ser-40, Ser-172, Ser-215, Thr-225	Systemic negative regulatory factor	Unknown
SC19	EF-P	Ser-148, Thr-176	Translation elongation factor, promoting polyproline protein synthesis	Decline
ZY05719	OsrP	Thr-48	Participation in antioxidant stress and maintenance of cell morphology	Decline

SS2 strains

Substrate proteins

Phosphorylation sites

Biological characteristics

Effect on virulence of deficiency

SC19

STK (autophosphorylation)

Thr-167, Ser-175

Phosphorylated kinase, regulating downstream signal transduction

Decline

ZY05719

GlmM

Ser-101

Catalyses the synthesis of peptidoglycan precursors, maintaining cell wall integrity

Decline

ZY05719

BglF

Ser-462

PTS system components, regulating β-glucoside uptake and metabolism

Decline

05ZYH33

DivIVA

Ser-145, Thr-199, Thr-211

Regulating cell polarity and division, directing the localisation of cell wall hydrolases

Unknown

SC19

FtsZ

Thr-217, Thr-233, Thr-349, Thr-383

A key protein in cell division, forming Z-rings to direct spindle assembly

Unknown

SC19

MapZ

Thr-26, Thr-66

Localise cleavage sites, stabilise Z-rings, and regulate membrane contraction

Unknown

ZY05719

Ccps

Thr-4, Thr-7

Regulating the activity of tyrosine phosphatase CpsB, influencing capsular synthesis

Decline

05ZYH33

Cps2C

Unknown

Tyrosine kinase associated with capsular synthesis

Decline

ZY05719

GntR

Ser-41

Transcription factors regulating antioxidant stress-related genes (such as nox)

Decline

ZY05719

FadR

Thr-230

Transcription factors regulate the arginine deiminase (ADI) pathway, influencing acid tolerance

Decline

ZY05719

LacI

Thr-29

LacI family transcription factors, presumed to be involved in metabolic regulation

Unknown

05ZYH33

CovR

Thr-45, Thr-148, Thr-150, Thr-159, Thr-168, Thr-194, Thr-219, Ser-40, Ser-172, Ser-215, Thr-225

Systemic negative regulatory factor

Unknown

SC19

EF-P

Ser-148, Thr-176

Translation elongation factor, promoting polyproline protein synthesis

Decline

ZY05719

OsrP

Thr-48

Participation in antioxidant stress and maintenance of cell morphology

Decline