<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense

ABSTRACT Pseudomonas aeruginosa, one of the most common pathogens in hospital-acquired infections, is tightly controlled by a multilayered regulatory network, including the quorum sensing system (QS), the type VI secretion system (T6SS), and resistance to host immunity. We found that the P. aerugino...

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Autores principales:	Yingchao Zhang, Chuan-min Zhou, Qinqin Pu, Qun Wu, Shirui Tan, Xiaolong Shao, Weitong Zhang, Yingpeng Xie, Rongpeng Li, Xue-jie Yu, Rui Wang, Liang Zhang, Min Wu, Xin Deng
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	AnvM Pseudomonas aeruginosa anaerobic Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b7fd56fa07ac405aa2139ad307eb9dee
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spelling	oai:doaj.org-article:b7fd56fa07ac405aa2139ad307eb9dee2021-11-15T16:22:09Z<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense10.1128/mBio.01362-192150-7511https://doaj.org/article/b7fd56fa07ac405aa2139ad307eb9dee2019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01362-19https://doaj.org/toc/2150-7511ABSTRACT Pseudomonas aeruginosa, one of the most common pathogens in hospital-acquired infections, is tightly controlled by a multilayered regulatory network, including the quorum sensing system (QS), the type VI secretion system (T6SS), and resistance to host immunity. We found that the P. aeruginosa 3880 (PA3880) gene, which encodes an unknown protein, acts as a regulator of anaerobic metabolism in response to oxidative stress and virulence in P. aeruginosa. More than 30 PA3880 homologs were found in other bacterial genomes, indicating that PA3880 is widely distributed in the Bacteria kingdom as a highly conserved gene. Deletion of the PA3880 gene changed the expression levels of more than 700 genes, including a group of virulence genes, under both aerobic and anaerobic conditions. To further study the mechanisms of PA3880-mediated regulation in virulence, we utilized a bacterial two-hybrid assay and found that the PA3880 protein interacted directly with QS regulator MvfR and anaerobic regulator Anr. Loss of the PA3880 protein significantly blunted the pathogenicity of P. aeruginosa, resulting in increased host survival, decreased bacterial burdens, reduced inflammatory responses, and fewer lung injuries in challenged mice hosts. Mechanistically, we found that Cys44 was a critical site for the full function of PA3880 in influencing alveolar macrophage phagocytosis and bacterial clearance. We also found that AnvM directly interacted with host receptors Toll-like receptor 2 (TLR2) and TLR5, which might lead to activation of the host immune response. Hence, we gave the name AnvM (anaerobic and virulence modulator) to the PA3880 protein. This characterization of AnvM could help to uncover new targets and strategies to treat P. aeruginosa infections. IMPORTANCE Infections by Pseudomonas aeruginosa, one of the most frequently isolated human pathogens, can create huge financial burdens. However, knowledge of the molecular mechanisms involved in the pathogenesis of P. aeruginosa remains elusive. We identified AnvM as a novel regulator of virulence in P. aeruginosa. Deletion of anvM altered the expression levels of more than 700 genes under aerobic and anaerobic conditions, including quorum sensing system genes and oxidative stress resistance genes. AnvM directly interacted with MvfR and Anr, thus regulating their downstream genes. More importantly, AnvM directly bound to TLR2 and TLR5, which turn on the host immune response. These findings provide insights into the significance of AnvM homologs in pathogenic bacteria and suggest a potential drug target against bacterial infection.Yingchao ZhangChuan-min ZhouQinqin PuQun WuShirui TanXiaolong ShaoWeitong ZhangYingpeng XieRongpeng LiXue-jie YuRui WangLiang ZhangMin WuXin DengAmerican Society for MicrobiologyarticleAnvMPseudomonas aeruginosaanaerobicMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	AnvM Pseudomonas aeruginosa anaerobic Microbiology QR1-502
spellingShingle	AnvM Pseudomonas aeruginosa anaerobic Microbiology QR1-502 Yingchao Zhang Chuan-min Zhou Qinqin Pu Qun Wu Shirui Tan Xiaolong Shao Weitong Zhang Yingpeng Xie Rongpeng Li Xue-jie Yu Rui Wang Liang Zhang Min Wu Xin Deng <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense
description	ABSTRACT Pseudomonas aeruginosa, one of the most common pathogens in hospital-acquired infections, is tightly controlled by a multilayered regulatory network, including the quorum sensing system (QS), the type VI secretion system (T6SS), and resistance to host immunity. We found that the P. aeruginosa 3880 (PA3880) gene, which encodes an unknown protein, acts as a regulator of anaerobic metabolism in response to oxidative stress and virulence in P. aeruginosa. More than 30 PA3880 homologs were found in other bacterial genomes, indicating that PA3880 is widely distributed in the Bacteria kingdom as a highly conserved gene. Deletion of the PA3880 gene changed the expression levels of more than 700 genes, including a group of virulence genes, under both aerobic and anaerobic conditions. To further study the mechanisms of PA3880-mediated regulation in virulence, we utilized a bacterial two-hybrid assay and found that the PA3880 protein interacted directly with QS regulator MvfR and anaerobic regulator Anr. Loss of the PA3880 protein significantly blunted the pathogenicity of P. aeruginosa, resulting in increased host survival, decreased bacterial burdens, reduced inflammatory responses, and fewer lung injuries in challenged mice hosts. Mechanistically, we found that Cys44 was a critical site for the full function of PA3880 in influencing alveolar macrophage phagocytosis and bacterial clearance. We also found that AnvM directly interacted with host receptors Toll-like receptor 2 (TLR2) and TLR5, which might lead to activation of the host immune response. Hence, we gave the name AnvM (anaerobic and virulence modulator) to the PA3880 protein. This characterization of AnvM could help to uncover new targets and strategies to treat P. aeruginosa infections. IMPORTANCE Infections by Pseudomonas aeruginosa, one of the most frequently isolated human pathogens, can create huge financial burdens. However, knowledge of the molecular mechanisms involved in the pathogenesis of P. aeruginosa remains elusive. We identified AnvM as a novel regulator of virulence in P. aeruginosa. Deletion of anvM altered the expression levels of more than 700 genes under aerobic and anaerobic conditions, including quorum sensing system genes and oxidative stress resistance genes. AnvM directly interacted with MvfR and Anr, thus regulating their downstream genes. More importantly, AnvM directly bound to TLR2 and TLR5, which turn on the host immune response. These findings provide insights into the significance of AnvM homologs in pathogenic bacteria and suggest a potential drug target against bacterial infection.
format	article
author	Yingchao Zhang Chuan-min Zhou Qinqin Pu Qun Wu Shirui Tan Xiaolong Shao Weitong Zhang Yingpeng Xie Rongpeng Li Xue-jie Yu Rui Wang Liang Zhang Min Wu Xin Deng
author_facet	Yingchao Zhang Chuan-min Zhou Qinqin Pu Qun Wu Shirui Tan Xiaolong Shao Weitong Zhang Yingpeng Xie Rongpeng Li Xue-jie Yu Rui Wang Liang Zhang Min Wu Xin Deng
author_sort	Yingchao Zhang
title	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense
title_short	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense
title_full	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense
title_fullStr	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense
title_full_unstemmed	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense
title_sort	<named-content content-type="genus-species">pseudomonas aeruginosa</named-content> regulatory protein anvm controls pathogenicity in anaerobic environments and impacts host defense
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b7fd56fa07ac405aa2139ad307eb9dee
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<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense

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