Pseudomonas aeruginosa two-component system CprRS regulates HigBA expression and bacterial cytotoxicity in response to LL-37 stress

被引:10
作者
Song, Yingjie [1 ]
Zhang, Siping [2 ]
Zhao, Ninglin [3 ]
Nong, Cheng [3 ]
He, Yongxing [2 ]
Bao, Rui [3 ]
机构
[1] Sichuan Normal Univ, Coll Life Sci, Chengdu, Peoples R China
[2] Lanzhou Univ, Sch Life Sci, Minist Educ, Key Lab Cell Act & Stress Adaptat, Lanzhou, Peoples R China
[3] Sichuan Univ, West China Hosp, Ctr Infect Dis, Div Infect Dis,State Key Lab Biotherapy, Chengdu, Peoples R China
基金
中国国家自然科学基金;
关键词
CATIONIC ANTIMICROBIAL PEPTIDES; IMMUNE-SYSTEM; POLYMYXIN-B; RESISTANCE; COLISTIN;
D O I
10.1371/journal.ppat.1011946
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Pseudomonas aeruginosa is a highly pathogenic bacterium known for its ability to sense and coordinate the production of virulence factors in response to host immune responses. However, the regulatory mechanisms underlying this process have remained largely elusive. In this study, we investigate the two-component system CprRS in P. aeruginosa and unveil the crucial role of the sensor protein CprS in sensing the human host defense peptide LL-37, thereby modulating bacterial virulence. We demonstrate that CprS acts as a phosphatase in the presence of LL-37, leading to the phosphorylation and activation of the response regulator CprR. The results prove that CprR directly recognizes a specific sequence within the promoter region of the HigBA toxin-antitoxin system, resulting in enhanced expression of the toxin HigB. Importantly, LL-37-induced HigB expression promotes the production of type III secretion system effectors, leading to reduced expression of proinflammatory cytokines and increased cytotoxicity towards macrophages. Moreover, mutations in cprS or cprR significantly impair bacterial survival in both macrophage and insect infection models. This study uncovers the regulatory mechanism of the CprRS system, enabling P. aeruginosa to detect and respond to human innate immune responses while maintaining a balanced virulence gene expression profile. Additionally, this study provides new evidence and insights into the complex regulatory system of T3SS in P. aeruginosa within the host environment, contributing to a better understanding of host-microbe communication and the development of novel strategies to combat bacterial infections.
引用
收藏
页数:25
相关论文
共 58 条
[1]   A tailored phosphoaspartate probe unravels CprR as a response regulator in Pseudomonas aeruginosa interkingdom signaling [J].
Allihn, Patrick W. A. ;
Hackl, Mathias W. ;
Ludwig, Christina ;
Hacker, Stephan M. ;
Sieber, Stephan A. .
CHEMICAL SCIENCE, 2021, 12 (13) :4763-4770
[2]   Host Antimicrobial Peptides: The Promise of New Treatment Strategies against Tuberculosis [J].
Arranz-Trullen, Javier ;
Lu, Lu ;
Pulido, David ;
Bhakta, Sanjib ;
Boix, Ester .
FRONTIERS IN IMMUNOLOGY, 2017, 8
[3]  
Ashby M, 2014, CURR OPIN INFECT DIS, V27, P258, DOI [10.1097/QCO.0000000000000066, 10.1097/QCO.0000000000000057]
[4]   Inactivation of the arn operon and loss of aminoarabinose on lipopolysaccharide as the cause of susceptibility to colistin in an atypical clinical isolate of proteus vulgaris [J].
Baron, Sophie ;
Leulmi, Zineb ;
Villard, Claude ;
Olaitan, Abiola Olumuyiwa ;
Telke, Amar A. ;
Rolain, Jean-Marc .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2018, 51 (03) :450-457
[5]   Antimicrobial Peptides: Mechanisms of Action and Resistance [J].
Bechinger, B. ;
Gorr, S. -U. .
JOURNAL OF DENTAL RESEARCH, 2017, 96 (03) :254-260
[6]   The role of the immune system in governing host-microbe interactions in the intestine [J].
Brown, Eric M. ;
Sadarangani, Manish ;
Finlay, B. Brett .
NATURE IMMUNOLOGY, 2013, 14 (07) :660-667
[7]   Polymyxin B versus colistin: an update [J].
Cai, Yiying ;
Lee, Winnie ;
Kwa, Andrea L. .
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, 2015, 13 (12) :1481-1497
[8]   Bacterial Evasion of Host Antimicrobial Peptide Defenses [J].
Cole, Jason N. ;
Nizet, Victor .
MICROBIOLOGY SPECTRUM, 2016, 4 (01)
[9]   Edwardsiella ictaluri T3SS Effector EseN Modulates Expression of Host Genes Involved in the Immune Response [J].
Dubytska, Lidiya P. ;
Koirala, Ranjan ;
Sanchez, Azhia ;
Thune, Ronald .
MICROORGANISMS, 2022, 10 (07)
[10]   The Two-Component System CprRS Senses Cationic Peptides and Triggers Adaptive Resistance in Pseudomonas aeruginosa Independently of ParRS [J].
Fernandez, Luca ;
Jenssen, Havard ;
Bains, Manjeet ;
Wiegand, Irith ;
Gooderham, W. James ;
Hancock, Robert E. W. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2012, 56 (12) :6212-6222