A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host

ABSTRACT Most pathogenic bacteria deliver virulence factors into host cytosol through type III secretion systems (T3SS) to perturb host immune responses. The expression of T3SS is often repressed in rich medium but is specifically induced in the host environment. The molecular mechanisms underlying...

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Autores principales:	Xiaofeng Zhou, Doron Teper, Maxuel O. Andrade, Tong Zhang, Sixue Chen, Wen-Yuan Song, Nian Wang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Lon protease type III secretion system Xanthomonas Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/51193f49435a45b9934095c428138cd0
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spelling	oai:doaj.org-article:51193f49435a45b9934095c428138cd02021-11-15T15:53:25ZA Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host10.1128/mBio.02146-172150-7511https://doaj.org/article/51193f49435a45b9934095c428138cd02018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02146-17https://doaj.org/toc/2150-7511ABSTRACT Most pathogenic bacteria deliver virulence factors into host cytosol through type III secretion systems (T3SS) to perturb host immune responses. The expression of T3SS is often repressed in rich medium but is specifically induced in the host environment. The molecular mechanisms underlying host-specific induction of T3SS expression is not completely understood. Here we demonstrate in Xanthomonas citri that host-induced phosphorylation of the ATP-dependent protease Lon stabilizes HrpG, the master regulator of T3SS, conferring bacterial virulence. Ser/Thr/Tyr phosphoproteome analysis revealed that phosphorylation of Lon at serine 654 occurs in the citrus host. In rich medium, Lon represses T3SS by degradation of HrpG via recognition of its N terminus. Genetic and biochemical data indicate that phosphorylation at serine 654 deactivates Lon proteolytic activity and attenuates HrpG proteolysis. Substitution of alanine for Lon serine 654 resulted in repression of T3SS gene expression in the citrus host through robust degradation of HrpG and reduced bacterial virulence. Our work reveals a novel mechanism for distinct regulation of bacterial T3SS in different environments. Additionally, our data provide new insight into the role of protein posttranslational modification in the regulation of bacterial virulence. IMPORTANCE Type III secretion systems (T3SS) are an essential virulence trait of many bacterial pathogens because of their indispensable role in the delivery of virulence factors. However, expression of T3SS in the noninfection stage is energy consuming. Here, we established a model to explain the differential regulation of T3SS in host and nonhost environments. When Xanthomonas cells are grown in rich medium, the T3SS regulator HrpG is targeted by Lon protease for proteolysis. The degradation of HrpG leads to downregulated expression of HrpX and the hrp/hrc genes. When Xanthomonas cells infect the host, specific plant stimuli can be perceived and induce Lon phosphorylation at serine 654. Phosphorylation on Lon attenuates its proteolytic activity and protects HrpG from degradation. Consequently, enhanced stability of HrpG activates HrpX and turns on bacterial T3SS in the host. Our work provides a novel molecular mechanism underlying host-dependent activation of bacterial T3SS.Xiaofeng ZhouDoron TeperMaxuel O. AndradeTong ZhangSixue ChenWen-Yuan SongNian WangAmerican Society for MicrobiologyarticleLon proteasetype III secretion systemXanthomonasMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lon protease type III secretion system Xanthomonas Microbiology QR1-502
spellingShingle	Lon protease type III secretion system Xanthomonas Microbiology QR1-502 Xiaofeng Zhou Doron Teper Maxuel O. Andrade Tong Zhang Sixue Chen Wen-Yuan Song Nian Wang A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host
description	ABSTRACT Most pathogenic bacteria deliver virulence factors into host cytosol through type III secretion systems (T3SS) to perturb host immune responses. The expression of T3SS is often repressed in rich medium but is specifically induced in the host environment. The molecular mechanisms underlying host-specific induction of T3SS expression is not completely understood. Here we demonstrate in Xanthomonas citri that host-induced phosphorylation of the ATP-dependent protease Lon stabilizes HrpG, the master regulator of T3SS, conferring bacterial virulence. Ser/Thr/Tyr phosphoproteome analysis revealed that phosphorylation of Lon at serine 654 occurs in the citrus host. In rich medium, Lon represses T3SS by degradation of HrpG via recognition of its N terminus. Genetic and biochemical data indicate that phosphorylation at serine 654 deactivates Lon proteolytic activity and attenuates HrpG proteolysis. Substitution of alanine for Lon serine 654 resulted in repression of T3SS gene expression in the citrus host through robust degradation of HrpG and reduced bacterial virulence. Our work reveals a novel mechanism for distinct regulation of bacterial T3SS in different environments. Additionally, our data provide new insight into the role of protein posttranslational modification in the regulation of bacterial virulence. IMPORTANCE Type III secretion systems (T3SS) are an essential virulence trait of many bacterial pathogens because of their indispensable role in the delivery of virulence factors. However, expression of T3SS in the noninfection stage is energy consuming. Here, we established a model to explain the differential regulation of T3SS in host and nonhost environments. When Xanthomonas cells are grown in rich medium, the T3SS regulator HrpG is targeted by Lon protease for proteolysis. The degradation of HrpG leads to downregulated expression of HrpX and the hrp/hrc genes. When Xanthomonas cells infect the host, specific plant stimuli can be perceived and induce Lon phosphorylation at serine 654. Phosphorylation on Lon attenuates its proteolytic activity and protects HrpG from degradation. Consequently, enhanced stability of HrpG activates HrpX and turns on bacterial T3SS in the host. Our work provides a novel molecular mechanism underlying host-dependent activation of bacterial T3SS.
format	article
author	Xiaofeng Zhou Doron Teper Maxuel O. Andrade Tong Zhang Sixue Chen Wen-Yuan Song Nian Wang
author_facet	Xiaofeng Zhou Doron Teper Maxuel O. Andrade Tong Zhang Sixue Chen Wen-Yuan Song Nian Wang
author_sort	Xiaofeng Zhou
title	A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host
title_short	A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host
title_full	A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host
title_fullStr	A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host
title_full_unstemmed	A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host
title_sort	phosphorylation switch on lon protease regulates bacterial type iii secretion system in host
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/51193f49435a45b9934095c428138cd0
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A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host

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