细菌双组分系统的耐药性及致病性研究进展

doi:10.11843/j.issn.0366-6964.2025.07.008

摘要/Abstract

摘要：

细菌双组分系统(two-component system，TCS)是普遍存在于生物体内的信号转导通路，能够感知和响应细胞内外的物理、化学和生物刺激，通过耦合传感和调节机制引起一系列的细胞反应。TCS是细菌感知和响应环境信号、调节生理行为最主要的机制，在细菌耐药性、致病性、生物被膜形成、毒力因子调控等方面均发挥着重要作用。TCS通过两个组分(传感器和效应器)的相互作用来调控基因表达和细胞行为，从而应对不利环境对细菌的影响，以达到增殖和入侵宿主的目的。本文综述了双组分系统的结构、功能、耐药性和致病性研究进展及双组分系统抑制剂，以期为新型抗菌药物研发及细菌防控提供参考。

关键词: 双组分系统, 结构, 功能, 耐药性, 致病性

Abstract:

The bacterial two-component system (TCS) is a widespread signaling transduction pathway in organisms, which can sense and respond to physical, chemical, and biological stimuli inside and outside the cell, and induce a series of cellular responses through coupled sensing and regulatory mechanisms.TCS is the principal mechanism for bacteria to sense and respond to environmental signals and regulate physiological behaviors, which plays a crucial role in bacterial drug resistance, pathogenicity, biofilm formation, virulence factor regulation, etc.TCS regulates gene expression and cellular behaviors through the interactions of the two components (sensors and effectors) to handle the impact of adverse environment on bacteria, therefore achieving the goal of proliferation and invasion of the host.This paper reviews the research advances in the structure, function, drug resistance regulation and pathogenicity, and inhibitors of the two-component system, providing a reference for the development of novel antimicrobial drugs and bacterial prevention and control.

Key words: two-component system, structure, function, drug resistance, pathogenicity

中图分类号:

S852.61

向令娴, 季倩宇, 单新新, 李琳. 细菌双组分系统的耐药性及致病性研究进展[J]. 畜牧兽医学报, 2025, 56(7): 3116-3128.

XIANG Lingxian, JI Qianyu, SHAN Xinxin, LI Lin. Advances in the Study of Drug Resistance and Pathogenicity of Bacterial Two-component Systems[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(7): 3116-3128.

图/表 3

图 1

图 2

表 1

参考文献 77

1	LI L , MA J , CHENG P , et al. Roles of two-component regulatory systems in Klebsiella pneumoniae: Regulation of virulence, antibiotic resistance, and stress responses[J]. Microbiol Res, 2023, 272, 127374.
2	郭佳成, 任宁宁, 郭爱珍, 等. 结核分枝杆菌PhoP-PhoR双组分系统研究进展[J]. 中国畜牧兽医, 2018, 45 (11): 3253- 3260.
	GUO J C , REN N N , GUO A Z , et al. Research progress on two-component system of Mycobacterium tuberculosis PhoP-PhoR[J]. Anijoumal Husbandry & Veterinary Medicine, 2018, 45 (11): 3253- 3260.
3	COLLINS M J , CHILDERS W S . The upcycled roles of pseudoenzymes in two-component signal transduction[J]. Curr Opin Microbiol, 2021, 61, 82- 90.
4	TIWARI S , JAMAL S B , HASSAN S S , et al. Two-component signal transduction systems of pathogenic bacteria as targets for antimicrobial therapy: An overview[J]. Front Microbiol, 2017, 8, 1878.
5	陈红玲. 表皮葡萄球菌VraR蛋白的原核表达及其生物学功能[D]. 大理: 大理大学, 2019.
	CHEN H L. Prokaryotic expression of VraR protein and its biological function research in Staphylococcus epidermidis[D]. Dali: Dali University, 2019. (in Chinese)
6	蔡杨, 凌保东. 双组分调控系统与细菌耐药性的关系及其抑制剂研究进展[J]. 医药导报, 2023, 42 (10): 1522- 1528. doi: 10.3870/j.issn.1004-0781.2023.10.018
	CAI Y , LING B D . Relationship between the two-component regulatory system and bacterial drug resistance and the research progress of its inhibitors[J]. Herald of Medicine, 2023, 42 (10): 1522- 1528. doi: 10.3870/j.issn.1004-0781.2023.10.018
7	李雷, 卫科科, 姜卫红, 等. 细菌双组分系统应答调控蛋白调控策略的多样性[J]. 中国科学: 生命科学, 2017, 47 (5): 462- 469.
	LI L , WEI K K , JIANG W H , et al. Diversity of regulatory strategies for two-component system response regulators in bacteria[J]. Scientia Sinica(Vitae), 2017, 47 (5): 462- 469.
8	GEISINGER E , ISBERG R R . Antibiotic modulation of capsular exopolysaccharide and virulence in Acinetobacter baumannii[J]. PLoS Pathog, 2015, 11 (2): e1004691.
9	王文静. 双组分系统BaeSR对鼠伤寒沙门菌耐药性的影响[D]. 合肥: 安徽农业大学, 2019.
	WANG W J. Effects of the two-component system BaeSR on the antibiotic resistance of Salmonella typhimurium[D]. Hefei: Anhui Agricultural University, 2019. (in Chinese)
10	KO D , CHOI S H . Mechanistic understanding of antibiotic resistance mediated by EnvZ/OmpR two-component system in Salmonella enterica servar Enteritidis[J]. J Antimicrob Chemother, 2022, 77 (9): 2419- 2428.
11	易正飞, 张耀东, 王瑶, 等. 双组分系统CpxR影响禽致病性大肠杆菌的耐药性、抗血清杀菌能力及毒力[J]. 畜牧兽医学报, 2021, 52 (4): 1053- 1060. doi: 10.11843/j.issn.0366-6964.2021.04.020
	YI Z F , ZHANG Y D , WANG Y , et al. Two component system CpxR contributes to the antibiotic resistance, serum Bactericidal resistance and virulence of avian pathogenic Escherichia coli[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52 (4): 1053- 1060. doi: 10.11843/j.issn.0366-6964.2021.04.020
12	OLAITAN A O , MORAND S , ROLAIN J M . Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria[J]. Front Microbiol, 2014 (5): 643.
13	MOSKOWITZ S M , ERNST R K , MILLER S I . PmrAB a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A[J]. J Bacteriol, 2004, 186 (2): 575- 579.
14	薛承斌. CpxRA双组分系统调控鼠伤寒沙门氏菌对多粘菌素耐药性的影响[D]. 秦皇岛: 河北科技师范学院, 2024.
	XUE C B. The CpxRA dual component system regulates the effect of Salmonella typhimurium on polymyxin resistance in mice[D]. Qinhuangdao: Hebei Normal University of Science & Technology University, 2024. (in Chinese)
15	PÉREZ-PALACIOS P , RODRÍGUEZ-OCHOA J L , VELÁZQUEZ-ESCUDERO A , et al. Implications of two-component systems EnvZ/OmpR and BaeS/BaeR in in vitro temocillin resistance in Escherichia coli[J]. J Antimicrob Chemother, 2024, 79 (3): 641- 647.
16	高海侠, 卢芳, 姜西迪, 等. 鼠伤寒沙门氏菌baeR过表达株的构建及其耐药性[J]. 微生物学通报, 2022, 49 (2): 659- 678.
	GAO H X , LU F , JIANG X D , et al. Construction and antibiotic resistance of a Salmonella typhimurium strain overexpressing baeR[J]. Microbiology China, 2022, 49 (2): 659- 678.
17	王诺. 粘质沙雷氏菌双组份系统BaeSR敲除株的构建及其抗生素耐药性变化的研究[D]. 重庆: 西南大学, 2023.
	WANG N. Construction and antibiotic resistance analysis of Serratia marcescens BaeSR two-component mutants[D]. Chongqing: Southwest University, 2023. (in Chinese)
18	武珊珊, 敬文宪, 陈启伟, 等. 鼠伤寒沙门氏菌双组分系统arcB基因缺失株的构建及药物敏感性分析[J]. 中国预防兽医学报, 2020, 42 (9): 879- 886.
	WU S S , JING W X , CHEN Q W , et al. Construction of a two-component system arcB gene deletion strain of Salmonella typhimurium and sensitivity analysis of antimicrobial agents[J]. Chinese Journal of Preventive Veterinary Medicine, 2020, 42 (9): 879- 886.
19	刘欢, 侯凯, 王崇刚. 鲍曼不动杆菌双组份系统调控AdeABC外排泵表达的研究[J]. 微生物学免疫学进展, 2024, 52 (1): 91- 96.
	LIU H , HOU K , WANG C G . Research updates on the regulatory role of two-component system on expression of AdeABC efflux pump in Acinetobacter baumannii[J]. Progress in Microbiology and Immunology, 2024, 52 (1): 91- 96.
20	DE GAETANO G V , LENTINI G , FAMÀ A , et al. Antimicrobial resistance: two-component regulatory systems and multidrug efflux pumps[J]. Antibiotics (Basel), 2023, 12 (6): 965.
21	徐军. 双组分系统BaeSR和外排泵AcrB调控鼠伤寒沙门菌耐药性的研究[D]. 合肥: 安徽农业大学, 2020.
	XU J. Study on the resistance regulation of the two-component system BaeSR and efflux pump AcrB to Salmonella typhimurium[D]. Hefei: Anhui Agricultural University, 2020. (in Chinese)
22	LEBLANC S K , OATES C W , RAIVIO T L . Characterization of the induction and cellular role of the BaeSR two-component envelope stress response of Escherichia coli[J]. J Bacteriol, 2011, 193 (13): 3367- 3375.
23	HU L , WANG C , LU W , et al. BaeSR activates type Ⅵ secretion system expression in porcine extra-intestinal pathogenic Escherichia coli to enhance bacterial resistance to zinc stress[J]. Microb Pathog, 2020, 147, 104357.
24	胡雨桐. 禽致病性大肠杆菌CpxRA双组分系统的机制探究[D]. 合肥: 安徽农业大学, 2023.
	HU Y T. Mechanism of CpxRA two-component system in avian pathogenic Escherichia coli[D]. Hefei: Anhui Agricultural University, 2023. (in Chinese)
25	HUANG H , SUN Y W , YUAN L , et al. Regulation of the two-component regulator CpxR on aminoglycosides and β-lactams resistance in Salmonella enterica serovar typhimurium[J]. Front Microbiol, 2016, 7, 604.
26	邹丹阳, 田晓雅, 夏万鹏, 等. CpxRA双组分系统对小肠结肠炎耶尔森菌环境耐受性和抗生素耐药性的影响[J]. 食品安全质量检测学报, 2024, 15 (9): 29- 36.
	ZOU D Y , TIAN X Y , XIA W P , et al. Effect of the CpxRA two-component system on environmental tolerance and antibiotic resistance of Yersinia enterocolitica in the small intestine[J]. Journal of Food Safety & Quality, 2024, 15 (9): 29- 36.
27	EUTSEY R , WANG G , MAIER R J . Role of a mutY DNA glycosylase in combating oxidative DNA damage in Helicobacter pylori[J]. DNA Repair (Amst), 2007, 6 (1): 19- 26.
28	WANG G , ALAMURI P , HUMAYUN M Z , et al. The Helicobacter pylori mutS protein confers protection from oxidative DNA damage[J]. Mol Microbiol, 2005, 58 (1): 166- 176.
29	李文. 双组分系统ArsRS参与幽门螺杆菌多耐药机制研究[D]. 济南: 山东大学, 2021.
	LI W. The mechanism research of two component system ArsRS involved in the multidrug resistance of Helicobacter pylori[D]. Jinan: Shandong University, 2021. (in Chinese)
30	KALLIPOLITIS B H , INGMER H , GAHAN C G , HILL C , et al. CesRK, a two-component signal transduction system in Listeria monocytogenes, responds to the presence of cell wall-acting antibiotics and affects β-lactam resistance[J]. Antimicrob Agents Chemother, 2003, 47 (11): 3421- 3429.
31	HOFER U . Antimicrobials: β-lactam sensor discovered[J]. Nat Rev Microbiol, 2016, 14 (4): 195.
32	BELITSKY B R . Histidine kinase-mediated cross-regulation of the vancomycin-resistance operon in Clostridioides difficile[J]. Mol Microbiol, 2024, 121 (6): 1182- 1199.
33	DEPARDIEU F , COURVALIN P , KOLB A . Binding sites of VanR_B and σ⁷⁰ RNA polymerase in the vanB vancomycin resistance operon of Enterococcus faecium BM4524[J]. Mol Microbiol, 2005, 57 (2): 550- 564.
34	何绿琴, 闫雪锋, 文心田, 等. 副猪嗜血杆菌qseB、qseC双基因缺失株的构建及生物学特性[J]. 畜牧兽医学报, 2022, 53 (2): 529- 537. doi: 10.11843/j.issn.0366-6964.2022.02.019
	HE L Q , YAN X F , WEN X T , et al. Construction and biological characteristic of Glaesserella parasuis strain with qseB qsec double gene deletion[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53 (2): 529- 537. doi: 10.11843/j.issn.0366-6964.2022.02.019
35	ZUO J , LIAO L , GAO Y , et al. Antibacterial effects of cinnamaldehyde and hesperitin on resistant Glaesserella parasuis by suppressing QseBC two-component system[J]. BMC Vet Res, 2025, 21 (1): 264.
36	李雪, 宁唤唤, 康健, 等. 结核分枝杆菌双组分系统PhoP蛋白的免疫学特性[J]. 中国人兽共患病学报, 2024, 40 (4): 352- 358.
	LI X , NING H H , KANG J , et al. Immuno logical characteristics of the PhoP protein of two-component system in Mycobacterium tuberculosis[J]. Chinese Journal of Zoonoses, 2024, 40 (4): 352- 358.
37	李泳榆, 汪川, 唐田. 沙门菌PhoP-PhoQ双组分系统信号响应机制研究进展[J]. 现代预防医学, 2017, 44 (22): 4168-4170, 4180.
	LI Y Y , WANG C , TANG T . Research progress on the signal response mechanism of Salmonella Phop-Phoq two-component system[J]. Modern Preventive Medicine, 2017, 44 (22): 4168-4170, 4180.
38	LIN M F , LIN Y Y , YEH H W , et al. Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility[J]. BMC Microbiology, 2014, 14, 119.
39	YAO Y , WUNIER W , MORIGEN M . Absence of the BaeR protein leads to the early initiation of DNA replication in Escherichia coli[J]. Genet Mol Res, 2015, 14 (4): 16888- 16895.
40	SUN H , HUANG D , PANG Y , et al. Key roles of two-component systems in intestinal signal sensing and virulence regulation in enterohemorrhagic Escherichia coli[J]. FEMS Microbiol Rev, 2024, 48 (6): fuae028.
41	FENG L , YANG B , XU Y , et al. Elucidation of a complete mechanical signaling and virulence activation pathway in Enterohemorrhagic Escherichia coli[J]. Cell Rep, 2022, 39 (1): 110614.
42	MEHDIZADEH GOHARI I , NAVARRO M A , LI J , et al. Pathogenicity and virulence of Clostridium perfringens[J]. Virulence, 2021, 12 (1): 723- 753.
43	王艳华, KHANMUZ, 许笑, 等. 产气荚膜梭菌VirS/VirR双组分系统调控机制研究进展[J]. 中国人兽共患病学报, 2019, 35 (10): 934-938, 956.
	WANG Y H , KHAN MUZ , XU X , et al. Research progress on regulatory mechanism of the VirS/VirR system in Clostridium perfringens[J]. Chinese Journal of Zoonoses, 2019, 35 (10): 934-938, 956.
44	王钊, 张万江. 结核分枝杆菌双组分系统MprAB的研究进展[J]. 中国病原生物学杂志, 2014, 9 (6): 577- 580.
	WANG Z , ZHANG W J . Advances in the study of the MprAB two-component system and Mycobacterium tuberculosis[J]. Journal of Pathogen Biology, 2014, 9 (6): 577- 580.
45	PANG X HOWARD S T . Regulation of the α-crystallin gene acr2 by the MprAB two-component system of Mycobacterium tuberculosis[J]. J Bacteriol, 2007, 189 (17): 6213- 6221.
46	关晓雯, 刘萌, 魏莲花. ArlRS双组分系统对金黄色葡萄球菌Ebh蛋白调控作用的研究进展[J]. 中国生物制品学杂志, 2023, 36 (8): 1010-1013, 1020.
	GUAN X W , LIU M , WEI L H . Research progress on regulation of Staphylococcus aureus Ebh protein by ArlRS two-component system[J]. Chinese Journal of Biologicals, 2023, 36 (8): 1010-1013, 1020.
47	LIN I C , HUSSAIN B , HSU B M , et al. Prevalence, genetic diversity, antimicrobial resistance, and toxigenic profile of Vibrio vulnificus isolated from aquatic environments in Taiwan, China[J]. Antibiotics (Basel), 2021, 10 (5): 505.
48	姚宁. 副溶血性弧菌双组分系统EnvZ/OmpR功能鉴定及其调节细菌耐碱机制研究[D]. 杭州: 浙江农林大学, 2022.
	YAO N. Identification of the function of the two-component system EnvZ/OmpR and its role in regulating alkaline stress tolerance in Vibrio parahaemolyticus[D]. Hangzhou: Zhejiang A & F University, 2022. (in Chinese)
49	马世林. 嗜水气单胞菌双组分系统ENVZ/OMPR的功能研究[D]. 武汉: 华中农业大学, 2021.
	MA S L. Functional analysis of two-component systems EnvZ/OmpR in Aeromonas hydrophila[D]. Wuhan: Huazhong Agricultural University, 2021. (in Chinese).
50	DU Z , ZHANG M , QIN Y , et al. The role and mechanisms of the two-component system EnvZ/OmpR on the intracellular survival of Aeromonas hydrophila[J]. J Fish Dis, 2022, 45 (11): 1609- 1621.
51	戴欣珏, 夏文浩, 任雨轩, 等. 钩端螺旋体OmpR家族相关TCS鉴定及功能初探[J]. 中国人兽共患病学报, 2024, 40 (3): 197- 202.
	DAI X J , XIA W H , REN Y X , et al. Identification and functional exploration of OmpR family TCS in Leptospira[J]. Chinese Journal of Zoonoses, 2024, 40 (3): 197- 202.
52	郭骞, 张钰, 方小伟, 等. 双组分系统resE/resD基因缺失对单增李斯特菌抗渗透压应激能力及致病性的影响[J]. 中国畜牧兽医, 2023, 50 (9): 3853- 3860.
	GUO Q , ZHANG Y , FANG X W , et al. Effects of two-component system resE/resD gene deletion on osmotic stress resistance and pathogenicity of Listeria monocytogenes.[J]. China Animal Husbandry & Veterinary Medicine, 2023, 50 (9): 3853- 3860.
53	ZHU Z H , LI H , YU P , et al. SlnR is a positive pathway-specific regulator for salinomycin biosynthesis in Streptomyces albus[J]. Appl Microbiol Biotechnol, 2017, 101 (4): 1547- 1557.
54	YOUNG D L , MIHALIAK C A , WEST S D , et al. Determination of spinosad and its metabolites in food and environmental matrices 3 immunoassay methods[J]. J Agric Food Chem, 2000, 48 (11): 5146- 5153.
55	万千千, 罗粤雯, 何昊城, 等. LytSR和PdtaSR双组分系统对须糖多孢菌丁烯基多杀菌素生物合成的影响[J]. 微生物学报, 2022, 62 (3): 1033- 1048.
	WANG Q Q , LUO Y W , HE H C , et al. The effect of LytSR and PdtaSR two-component systems on the biosynthesis of butenyl-spinosyn of Saccharopolyspora pogona[J]. Acta Microbiologica Sinica, 2022, 62 (3): 1033- 1048.
56	王玖清. 沙门氏菌双组分系统QseEF信号转导与Ⅲ型分泌系统底物分选机制探究[D]. 济南: 山东大学, 2022.
	WANG J Q. Study on the signal transduction mechanism of QseEF and substrate sorting mechanism of T3SS in Salmonella[D]. Jinan: Shandong University, 2022. (in Chinese)
57	MOREIRA C G , SPERANDIO V . Interplay between the QseC and QseE bacterial adrenergic sensor kinases in Salmonella enterica serovar Typhimurium pathogenesis[J]. Infect Immun, 2012, 80 (12): 4344- 4353.
58	MA J B , AHMED M A H , SHAO S , et al. The QseE-QseF two-component system: A key mediator of epinephrine-regulated virulence in the marine pathogen Edwardsiella piscicida[J]. Microbiol Res, 2024, 279, 127561.
59	CHOI C H , MUN S , OH M H . Identification and characterization of Acinetobacter nosocomialis BfmRS, two-component regulatory system, essential for biofilm development[J]. Genes Genomics, 2024, 46 (5): 531- 539.
60	PALETHORPE S , FARROW 3RD J M , WELLS G , et al. Acinetobacter baumannii regulates its stress responses via the bfmRS two-component regulatory system[J]. J Bacteriol, 2022, 204 (2): e0049421.
61	周子严, 於亭, 张毓宸, 等. 鲍曼不动杆菌双组分系统bfmR基因缺失株构建及其生物学特性分析[J]. 扬州大学学报(农业与生命科学版), 2024, 45 (4): 11- 19.
	ZHOU Z Y , YU T , ZHANG Y C , et al. Construction of two-component system bfmR gene deletion strain of Acinetobacter baumannii andanalysis of its biological characteristic[J]. Journal of Yangzhou University (Agnicultural and Life Science Edition), 2024, 45 (4): 11- 19.
62	MAJDI C , MEFFRE P , BENFODDA Z . Recent advances in the development of bacterial response regulators inhibitors as antibacterial and/or antibiotic adjuvant agent: A new approach to combat bacterial resistance[J]. Bioorg Chem, 2024, 150, 107606.
63	FIHN C A , LEMBKE H K , GAULIN J , et al. Evaluation of expanded 2-aminobenzothiazole library as inhibitors of a model histidine kinase and virulence suppressors in Pseudomonas aeruginosa[J]. Bioorg Chem, 2024, 153, 107840.
64	BESANT P G , LASKER M V , BUI C D , et al. Inhibition of branched-chain alpha-keto acid dehydrogenase kinase and Sln1 yeast histidine kinase by the antifungal antibiotic radicicol[J]. Mol Pharmacol, 2002, 62 (2): 289- 296.
65	OKADA A , IGARASHI M , OKAJIMA T , et al. Walkmycin B targets WalK (YycG), a histidine kinase essential for bacterial cell growth[J]. J Antibiot (Tokyo), 2010, 63 (2): 89- 94.
66	MACIELAG M J , DEMERS J P , FRAGA-SPANO S A , et al. Substituted salicylanilides as inhibitors of two-component regulatory systems in bacterial[J]. J Med Chem, 1998, 41 (16): 2939- 2945.
67	KUMAGAI Y , CHENG Z H , LIN M Q , et al. Biochemical activities of three pairs of Ehrlichia chaffeensis two-component regulatory system proteins involved in inhibition of lysosomal fusion[J]. Infect Immun, 2006, 74 (9): 5014- 5022.
68	KANOJIA R M , MURRAY W , BERNSTEIN J , et al. 6-Oxa isosteres of anacardic acids as potent inhibitors of bacterial histidine protein kinase(HPK)-mediated two-component regulatory systems[J]. Bioorg Med Chem Lett, 1999, 9 (20): 2947- 2952.
69	LOBERTTI C A , CABEZUDO I , GIZZI F O , et al. An allosteric inhibitor of the PhoQ histidine kinase with therapeutic potential against Salmonella infection[J]. J Antimicrob Chemother, 2024, 79 (8): 1820- 1830.
70	HO Y H , SUNG T C , CHEN C S . Lactoferricin B inhibits the phosphorylation of the two-component system response regulators BasR and CreB[J]. Mol Cell Proteomics, 2012, 11 (4): M111.014720.
71	ROYCHOUDHURY S , ZIELINSKI N A , NINFA A J , et al. Inhibitors of two-component signal transduction systems: Inhibition of alginate gene activation in Pseudomonas aeruginosa[J]. Proc Natl Acad Sci U S A, 1993, 90 (3): 965- 969.
72	TIWARI S , DA COSTA MP , ALMEIDA S , et al. C.pseudotuberculosis Phop confers virulence and may be targeted by natural compounds[J]. Integr Biol (Camb), 2014, 6 (11): 1088- 1099.
73	TAN S , CHO K , NODWELL J R . A defect in cell wall recycling confers antibiotic resistance and sensitivity in Staphylococcus aureus[J]. J Biol Chem, 2022, 298 (10): 102473.
74	HIRAKAWA H , KURUSHIMA J , HASHIMOTO Y , et al. Progress overview of bacterial two-Component regulatory systems as potential targets for antimicrobial Chemotherapy[J]. Antibiotics (Basel), 2020, 9 (10): 635.
75	郎晨晓, 罗欣, 朱立贤, 等. 双组分调控系统及其对细菌诱导性耐酸响应调控机理的研究进展[J]. 食品科学, 2019, 40 (15): 359- 366.
	LANG C X , LUO X , ZHU L X , et al. Two-component regulatory system and its mechanism of action in regulating bacterial acid tolerance response: a review[J]. Food Science, 2019, 40 (15): 359- 366.
76	LIU F , YAO Q HUANG J , et al. The two-component system CpxA/CpxR is critical for full virulence in Actinobacillus pleuropneumoniae[J]. Front Microbiol, 2022, 13, 1029426.
77	FU Y , LI J , WANG J , et al. Development of a two component system based biosensor with high sensitivity for the detection of copper ions[J]. Commun Biol, 2024, 7 (1): 1407.

抑制剂 Inhibitors	作用部位 Region of action	抑制效应 Inhibition effect
传感器激酶抑制剂 Sensor kinase inhibitors
不饱和脂肪酸 Unsaturated fatty acids	KinA	自磷酸化 Auto-phosphorylation
卤代苯基噻唑 Halogenated phenylthiazole	AlgR2、VanS、CheA、NtrB	自磷酸化/磷酸转移 Auto-phosphorylation/phosphotransfer
水杨酰苯胺类 Salicylanilides, etc.	许多传感器激酶 Many sensor kinases	蛋白质聚集 Protein aggregation
噻吩并吡啶化合物 TEP	AlgR2	自磷酸化 Auto-phosphorylation
walkmycin B	WalKR	自磷酸化 Auto-phosphorylation
酪胺衍生物 Tyramine derivatives	VanSR	自磷酸化 Auto-phosphorylation
苯并恶唑嗪酮类 Benzoxazinones	许多传感器激酶 Many sensor kinases	自磷酸化 Auto-phosphorylation
RR抑制剂 Response regulator inhibitors
乳铁蛋白B Lactoferricin B	BasR、CreB	磷酸化 Phosphorylation
大黄酸 Rhein	PhoP	磷酸化 Phosphorylation
烷基咪唑衍生物 Alkyl imidazole derivatives	AlgR1	与靶DNA结合 Binding to target DNA
walrycin A walrycin B	AlgR1	与靶DNA结合 Binding to target DNA

[1]	李茜, 高欢, 符爽, 锁卓, 代悦, 陈晨, 李荣天, 冷静. 消化道厌氧真菌及与其他微生物的互作关系[J]. 畜牧兽医学报, 2025, 56(7): 3096-3106.
[2]	张嘉良, 黄畅, 杨永林, 杨华, 白文林, 马月辉, 赵倩君. 基于50K液相芯片的中国绵羊群体遗传结构与羊毛性状选择信号分析[J]. 畜牧兽医学报, 2025, 56(7): 3164-3176.
[3]	孔祥鹤, 苏欣雨, 钟一铭, 卢赵梓暄, 廖献茂, 张哲, 张旭, 高萌萌, 周玉龙, 樊祜卿. 黑龙江省地区犊牛腹泻源致病性大肠杆菌流行情况调查、毒力基因及耐药性分析[J]. 畜牧兽医学报, 2025, 56(7): 3390-3398.
[4]	潘华, 孙磊, 张军, 刘莉莉, 马文刚, 曹爱智, 吕明斌. 胆汁酸抑菌机制及结构改性的研究进展[J]. 畜牧兽医学报, 2025, 56(6): 2546-2554.
[5]	李文超, 李维俏, 李欣, 王家庆, 张雅为, 李俊平. 动物源细菌耐药性及中药消减耐药性的研究进展[J]. 畜牧兽医学报, 2025, 56(6): 2555-2576.
[6]	董娇娇, 丁虹, 张寅梁, 张冉, 刘华格, 臧素敏, 张振红, 周荣艳, 李兰会. 鸡白痢沙门菌感染太行鸡盲肠菌群的差异及功能分析[J]. 畜牧兽医学报, 2025, 56(6): 2741-2751.
[7]	陈云龙, 樊港, 樊心怡, 郭永超, 张鑫淼, 王妍, 张仕强. 一株具有多位点核苷酸替换的新型猪圆环病毒2d亚型毒株的分离与鉴定[J]. 畜牧兽医学报, 2025, 56(6): 3032-3040.
[8]	王勤倩, 高振东, 陆颖, 马若珊, 邓卫东, 和晓明. 全基因组重测序在中国地方黄牛上的研究进展[J]. 畜牧兽医学报, 2025, 56(5): 2026-2037.
[9]	秦小霞, 甘海清, 佘高进, 刘勇, 黄兴国, 陈丽蓉, 杨玲媛. 油茶籽粕的活性成分、生物学功能及其在畜禽生产中的应用研究进展[J]. 畜牧兽医学报, 2025, 56(5): 2070-2081.
[10]	王亚楠, 郭雅茹, 姜艳平, 崔文, 李佳璇, 李一经, 王丽. 猪轮状病毒的分离鉴定及其致病性分析[J]. 畜牧兽医学报, 2025, 56(5): 2259-2269.
[11]	王锦祥, 苏进博, 付环茹, 孙世坤, 高承芳, 陈冬金, 桑雷, 谢喜平. 兔源A型多杀性巴氏杆菌Pm3和Pm6的致病性和基因组特征分析[J]. 畜牧兽医学报, 2025, 56(5): 2340-2352.
[12]	石金川, 孙淼, 孟令浩, 王永强, 耿超, 齐朝鲁蒙, 陈亨利, 王梓, 刘锴. 赛鸽源大肠杆菌耐药性检测及多重耐药菌株的全基因组测序分析[J]. 畜牧兽医学报, 2025, 56(5): 2372-2382.
[13]	陈婷, 崔亚东, 兰伟, 孔祥峰. 氨基葡萄糖的功能及其在动物生产中的应用[J]. 畜牧兽医学报, 2025, 56(4): 1518-1526.
[14]	吴俊杰, 吕世明, 龙小霞, 王忠, 王立琦. 中药及活性成分抗耐药菌作用及其机制研究进展[J]. 畜牧兽医学报, 2025, 56(4): 1632-1647.
[15]	朱云, 王钰明, 孙晓晓, 陈辉, 赵峰, 解竞静, 陈一凡, 萨仁娜. 低蛋白多元化饲粮添加玉米蛋白粉对白羽肉鸡生长性能和消化特性的影响[J]. 畜牧兽医学报, 2025, 56(4): 1802-1812.