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
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机构:
Sichuan Normal Univ, Coll Life Sci, Chengdu, Peoples R ChinaSichuan Normal Univ, Coll Life Sci, Chengdu, Peoples R China
Song, Yingjie
[1
]
Zhang, Siping
论文数: 0引用数: 0
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机构:
Lanzhou Univ, Sch Life Sci, Minist Educ, Key Lab Cell Act & Stress Adaptat, Lanzhou, Peoples R ChinaSichuan Normal Univ, Coll Life Sci, Chengdu, Peoples R China
Zhang, Siping
[2
]
Zhao, Ninglin
论文数: 0引用数: 0
h-index: 0
机构:
Sichuan Univ, West China Hosp, Ctr Infect Dis, Div Infect Dis,State Key Lab Biotherapy, Chengdu, Peoples R ChinaSichuan Normal Univ, Coll Life Sci, Chengdu, Peoples R China
Zhao, Ninglin
[3
]
Nong, Cheng
论文数: 0引用数: 0
h-index: 0
机构:
Sichuan Univ, West China Hosp, Ctr Infect Dis, Div Infect Dis,State Key Lab Biotherapy, Chengdu, Peoples R ChinaSichuan Normal Univ, Coll Life Sci, Chengdu, Peoples R China
Nong, Cheng
[3
]
He, Yongxing
论文数: 0引用数: 0
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机构:
Lanzhou Univ, Sch Life Sci, Minist Educ, Key Lab Cell Act & Stress Adaptat, Lanzhou, Peoples R ChinaSichuan Normal Univ, Coll Life Sci, Chengdu, Peoples R China
He, Yongxing
[2
]
Bao, Rui
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机构:
Sichuan Univ, West China Hosp, Ctr Infect Dis, Div Infect Dis,State Key Lab Biotherapy, Chengdu, Peoples R ChinaSichuan Normal Univ, Coll Life Sci, Chengdu, Peoples R China
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
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.
机构:
Univ Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Birkbeck Univ London, Mycobacteria Res Lab, Dept Biol Sci, Inst Struct & Mol Biol, London, EnglandUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Arranz-Trullen, Javier
;
Lu, Lu
论文数: 0引用数: 0
h-index: 0
机构:
Univ Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, SpainUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Lu, Lu
;
Pulido, David
论文数: 0引用数: 0
h-index: 0
机构:
Univ Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Univ Oxford, Nuffield Dept Med, Oxford, EnglandUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Pulido, David
;
Bhakta, Sanjib
论文数: 0引用数: 0
h-index: 0
机构:
Birkbeck Univ London, Mycobacteria Res Lab, Dept Biol Sci, Inst Struct & Mol Biol, London, EnglandUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Bhakta, Sanjib
;
Boix, Ester
论文数: 0引用数: 0
h-index: 0
机构:
Univ Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, SpainUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
机构:
Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, CanadaUniv British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
Brown, Eric M.
;
Sadarangani, Manish
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada
British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada
Univ Oxford, Dept Pediat, Oxford, EnglandUniv British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
Sadarangani, Manish
;
Finlay, B. Brett
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, CanadaUniv British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
机构:
Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Qld 4072, Australia
Univ Queensland, Australian Infect Dis Res Ctr, St Lucia, Qld 4072, AustraliaUniv Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
Cole, Jason N.
;
Nizet, Victor
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
Univ Calif San Diego, Ctr Immun Infect & Inflammat, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
机构:
Univ Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Birkbeck Univ London, Mycobacteria Res Lab, Dept Biol Sci, Inst Struct & Mol Biol, London, EnglandUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Arranz-Trullen, Javier
;
Lu, Lu
论文数: 0引用数: 0
h-index: 0
机构:
Univ Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, SpainUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Lu, Lu
;
Pulido, David
论文数: 0引用数: 0
h-index: 0
机构:
Univ Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Univ Oxford, Nuffield Dept Med, Oxford, EnglandUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Pulido, David
;
Bhakta, Sanjib
论文数: 0引用数: 0
h-index: 0
机构:
Birkbeck Univ London, Mycobacteria Res Lab, Dept Biol Sci, Inst Struct & Mol Biol, London, EnglandUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
Bhakta, Sanjib
;
Boix, Ester
论文数: 0引用数: 0
h-index: 0
机构:
Univ Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, SpainUniv Autonoma Barcelona, Fac Biosci, Dept Biochem & Mol Biol, Cerdanyola Del Valles, Spain
机构:
Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, CanadaUniv British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
Brown, Eric M.
;
Sadarangani, Manish
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada
British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada
Univ Oxford, Dept Pediat, Oxford, EnglandUniv British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
Sadarangani, Manish
;
Finlay, B. Brett
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, CanadaUniv British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada
机构:
Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Qld 4072, Australia
Univ Queensland, Australian Infect Dis Res Ctr, St Lucia, Qld 4072, AustraliaUniv Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
Cole, Jason N.
;
Nizet, Victor
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
Univ Calif San Diego, Ctr Immun Infect & Inflammat, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA