CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria

ABSTRACT Contact-dependent growth inhibition (CDI) systems encode CdiA effectors, which bind to specific receptors on neighboring bacteria and deliver C-terminal toxin domains to suppress target cell growth. Two classes of CdiA effectors that bind distinct cell surface receptors have been identified...

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Autores principales:	Zachary C. Ruhe, Josephine Y. Nguyen, Jing Xiong, Sanna Koskiniemi, Christina M. Beck, Basil R. Perkins, David A. Low, Christopher S. Hayes
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	bacterial competition cell-cell adhesion self/nonself discrimination toxin immunity proteins type V secretion system Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6c77590bbaf34ce5bd811392d96d7a98
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spelling	oai:doaj.org-article:6c77590bbaf34ce5bd811392d96d7a982021-11-15T15:51:00ZCdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria10.1128/mBio.00290-172150-7511https://doaj.org/article/6c77590bbaf34ce5bd811392d96d7a982017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00290-17https://doaj.org/toc/2150-7511ABSTRACT Contact-dependent growth inhibition (CDI) systems encode CdiA effectors, which bind to specific receptors on neighboring bacteria and deliver C-terminal toxin domains to suppress target cell growth. Two classes of CdiA effectors that bind distinct cell surface receptors have been identified, but the molecular basis of receptor specificity is not understood. Alignment of BamA-specific CdiAEC93 from Escherichia coli EC93 and OmpC-specific CdiAEC536 from E. coli 536 suggests that the receptor-binding domain resides within a central region that varies between the two effectors. In support of this hypothesis, we find that CdiAEC93 fragments containing residues Arg1358 to Phe1646 bind specifically to purified BamA. Moreover, chimeric CdiAEC93 that carries the corresponding sequence from CdiAEC536 is endowed with OmpC-binding activity, demonstrating that this region dictates receptor specificity. A survey of E. coli CdiA proteins reveals two additional effector classes, which presumably recognize distinct receptors. Using a genetic approach, we identify the outer membrane nucleoside transporter Tsx as the receptor for a third class of CdiA effectors. Thus, CDI systems exploit multiple outer membrane proteins to identify and engage target cells. These results underscore the modularity of CdiA proteins and suggest that novel effectors can be constructed through genetic recombination to interchange different receptor-binding domains and toxic payloads. IMPORTANCE CdiB/CdiA two-partner secretion proteins mediate interbacterial competition through the delivery of polymorphic toxin domains. This process, known as contact-dependent growth inhibition (CDI), requires stable interactions between the CdiA effector protein and specific receptors on the surface of target bacteria. Here, we localize the receptor-binding domain to the central region of E. coli CdiA. Receptor-binding domains vary between CdiA proteins, and E. coli strains collectively encode at least four distinct effector classes. Further, we show that receptor specificity can be altered by exchanging receptor-binding regions, demonstrating the modularity of this domain. We propose that novel CdiA effectors are naturally generated through genetic recombination to interchange different receptor-binding domains and toxin payloads.Zachary C. RuheJosephine Y. NguyenJing XiongSanna KoskiniemiChristina M. BeckBasil R. PerkinsDavid A. LowChristopher S. HayesAmerican Society for Microbiologyarticlebacterial competitioncell-cell adhesionself/nonself discriminationtoxin immunity proteinstype V secretion systemMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacterial competition cell-cell adhesion self/nonself discrimination toxin immunity proteins type V secretion system Microbiology QR1-502
spellingShingle	bacterial competition cell-cell adhesion self/nonself discrimination toxin immunity proteins type V secretion system Microbiology QR1-502 Zachary C. Ruhe Josephine Y. Nguyen Jing Xiong Sanna Koskiniemi Christina M. Beck Basil R. Perkins David A. Low Christopher S. Hayes CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria
description	ABSTRACT Contact-dependent growth inhibition (CDI) systems encode CdiA effectors, which bind to specific receptors on neighboring bacteria and deliver C-terminal toxin domains to suppress target cell growth. Two classes of CdiA effectors that bind distinct cell surface receptors have been identified, but the molecular basis of receptor specificity is not understood. Alignment of BamA-specific CdiAEC93 from Escherichia coli EC93 and OmpC-specific CdiAEC536 from E. coli 536 suggests that the receptor-binding domain resides within a central region that varies between the two effectors. In support of this hypothesis, we find that CdiAEC93 fragments containing residues Arg1358 to Phe1646 bind specifically to purified BamA. Moreover, chimeric CdiAEC93 that carries the corresponding sequence from CdiAEC536 is endowed with OmpC-binding activity, demonstrating that this region dictates receptor specificity. A survey of E. coli CdiA proteins reveals two additional effector classes, which presumably recognize distinct receptors. Using a genetic approach, we identify the outer membrane nucleoside transporter Tsx as the receptor for a third class of CdiA effectors. Thus, CDI systems exploit multiple outer membrane proteins to identify and engage target cells. These results underscore the modularity of CdiA proteins and suggest that novel effectors can be constructed through genetic recombination to interchange different receptor-binding domains and toxic payloads. IMPORTANCE CdiB/CdiA two-partner secretion proteins mediate interbacterial competition through the delivery of polymorphic toxin domains. This process, known as contact-dependent growth inhibition (CDI), requires stable interactions between the CdiA effector protein and specific receptors on the surface of target bacteria. Here, we localize the receptor-binding domain to the central region of E. coli CdiA. Receptor-binding domains vary between CdiA proteins, and E. coli strains collectively encode at least four distinct effector classes. Further, we show that receptor specificity can be altered by exchanging receptor-binding regions, demonstrating the modularity of this domain. We propose that novel CdiA effectors are naturally generated through genetic recombination to interchange different receptor-binding domains and toxin payloads.
format	article
author	Zachary C. Ruhe Josephine Y. Nguyen Jing Xiong Sanna Koskiniemi Christina M. Beck Basil R. Perkins David A. Low Christopher S. Hayes
author_facet	Zachary C. Ruhe Josephine Y. Nguyen Jing Xiong Sanna Koskiniemi Christina M. Beck Basil R. Perkins David A. Low Christopher S. Hayes
author_sort	Zachary C. Ruhe
title	CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria
title_short	CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria
title_full	CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria
title_fullStr	CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria
title_full_unstemmed	CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria
title_sort	cdia effectors use modular receptor-binding domains to recognize target bacteria
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/6c77590bbaf34ce5bd811392d96d7a98
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CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria

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