Force-Induced Strengthening of the Interaction between <italic toggle="yes">Staphylococcus aureus</italic> Clumping Factor B and Loricrin

ABSTRACT Bacterial pathogens that colonize host surfaces are subjected to physical stresses such as fluid flow and cell surface contacts. How bacteria respond to such mechanical cues is an important yet poorly understood issue. Staphylococcus aureus uses a repertoire of surface proteins to resist sh...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Pauline Vitry, Claire Valotteau, Cécile Feuillie, Simon Bernard, David Alsteens, Joan A. Geoghegan, Yves F. Dufrêne
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	atomic force microscopy cell adhesion physical stress skin Staphylococcus aureus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/dd2ed11d1e2847eb979c775c523b0726
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:dd2ed11d1e2847eb979c775c523b0726
record_format	dspace
spelling	oai:doaj.org-article:dd2ed11d1e2847eb979c775c523b07262021-11-15T15:51:56ZForce-Induced Strengthening of the Interaction between <italic toggle="yes">Staphylococcus aureus</italic> Clumping Factor B and Loricrin10.1128/mBio.01748-172150-7511https://doaj.org/article/dd2ed11d1e2847eb979c775c523b07262017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01748-17https://doaj.org/toc/2150-7511ABSTRACT Bacterial pathogens that colonize host surfaces are subjected to physical stresses such as fluid flow and cell surface contacts. How bacteria respond to such mechanical cues is an important yet poorly understood issue. Staphylococcus aureus uses a repertoire of surface proteins to resist shear stress during the colonization of host tissues, but whether their adhesive functions can be modulated by physical forces is not known. Here, we show that the interaction of S. aureus clumping factor B (ClfB) with the squamous epithelial cell envelope protein loricrin is enhanced by mechanical force. We find that ClfB mediates S. aureus adhesion to loricrin through weak and strong molecular interactions both in a laboratory strain and in a clinical isolate. Strong forces (~1,500 pN), among the strongest measured for a receptor-ligand bond, are consistent with a high-affinity “dock, lock, and latch” binding mechanism involving dynamic conformational changes in the adhesin. Notably, we demonstrate that the strength of the ClfB-loricrin bond increases as mechanical force is applied. These findings favor a two-state model whereby bacterial adhesion to loricrin is enhanced through force-induced conformational changes in the ClfB molecule, from a weakly binding folded state to a strongly binding extended state. This force-sensitive mechanism may provide S. aureus with a means to finely tune its adhesive properties during the colonization of host surfaces, helping cells to attach firmly under high shear stress and to detach and spread under low shear stress. IMPORTANCE Staphylococcus aureus colonizes the human skin and the nose and can cause various disorders, including superficial skin lesions and invasive infections. During nasal colonization, the S. aureus surface protein clumping factor B (ClfB) binds to the squamous epithelial cell envelope protein loricrin, but the molecular interactions involved are poorly understood. Here, we unravel the molecular mechanism guiding the ClfB-loricrin interaction. We show that the ClfB-loricrin bond is remarkably strong, consistent with a high-affinity “dock, lock, and latch” binding mechanism. We discover that the ClfB-loricrin interaction is enhanced under tensile loading, thus providing evidence that the function of an S. aureus surface protein can be activated by physical stress.Pauline VitryClaire ValotteauCécile FeuillieSimon BernardDavid AlsteensJoan A. GeogheganYves F. DufrêneAmerican Society for Microbiologyarticleatomic force microscopycell adhesionphysical stressskinStaphylococcus aureusMicrobiologyQR1-502ENmBio, Vol 8, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	atomic force microscopy cell adhesion physical stress skin Staphylococcus aureus Microbiology QR1-502
spellingShingle	atomic force microscopy cell adhesion physical stress skin Staphylococcus aureus Microbiology QR1-502 Pauline Vitry Claire Valotteau Cécile Feuillie Simon Bernard David Alsteens Joan A. Geoghegan Yves F. Dufrêne Force-Induced Strengthening of the Interaction between <italic toggle="yes">Staphylococcus aureus</italic> Clumping Factor B and Loricrin
description	ABSTRACT Bacterial pathogens that colonize host surfaces are subjected to physical stresses such as fluid flow and cell surface contacts. How bacteria respond to such mechanical cues is an important yet poorly understood issue. Staphylococcus aureus uses a repertoire of surface proteins to resist shear stress during the colonization of host tissues, but whether their adhesive functions can be modulated by physical forces is not known. Here, we show that the interaction of S. aureus clumping factor B (ClfB) with the squamous epithelial cell envelope protein loricrin is enhanced by mechanical force. We find that ClfB mediates S. aureus adhesion to loricrin through weak and strong molecular interactions both in a laboratory strain and in a clinical isolate. Strong forces (~1,500 pN), among the strongest measured for a receptor-ligand bond, are consistent with a high-affinity “dock, lock, and latch” binding mechanism involving dynamic conformational changes in the adhesin. Notably, we demonstrate that the strength of the ClfB-loricrin bond increases as mechanical force is applied. These findings favor a two-state model whereby bacterial adhesion to loricrin is enhanced through force-induced conformational changes in the ClfB molecule, from a weakly binding folded state to a strongly binding extended state. This force-sensitive mechanism may provide S. aureus with a means to finely tune its adhesive properties during the colonization of host surfaces, helping cells to attach firmly under high shear stress and to detach and spread under low shear stress. IMPORTANCE Staphylococcus aureus colonizes the human skin and the nose and can cause various disorders, including superficial skin lesions and invasive infections. During nasal colonization, the S. aureus surface protein clumping factor B (ClfB) binds to the squamous epithelial cell envelope protein loricrin, but the molecular interactions involved are poorly understood. Here, we unravel the molecular mechanism guiding the ClfB-loricrin interaction. We show that the ClfB-loricrin bond is remarkably strong, consistent with a high-affinity “dock, lock, and latch” binding mechanism. We discover that the ClfB-loricrin interaction is enhanced under tensile loading, thus providing evidence that the function of an S. aureus surface protein can be activated by physical stress.
format	article
author	Pauline Vitry Claire Valotteau Cécile Feuillie Simon Bernard David Alsteens Joan A. Geoghegan Yves F. Dufrêne
author_facet	Pauline Vitry Claire Valotteau Cécile Feuillie Simon Bernard David Alsteens Joan A. Geoghegan Yves F. Dufrêne
author_sort	Pauline Vitry
title	Force-Induced Strengthening of the Interaction between <italic toggle="yes">Staphylococcus aureus</italic> Clumping Factor B and Loricrin
title_short	Force-Induced Strengthening of the Interaction between <italic toggle="yes">Staphylococcus aureus</italic> Clumping Factor B and Loricrin
title_full	Force-Induced Strengthening of the Interaction between <italic toggle="yes">Staphylococcus aureus</italic> Clumping Factor B and Loricrin
title_fullStr	Force-Induced Strengthening of the Interaction between <italic toggle="yes">Staphylococcus aureus</italic> Clumping Factor B and Loricrin
title_full_unstemmed	Force-Induced Strengthening of the Interaction between <italic toggle="yes">Staphylococcus aureus</italic> Clumping Factor B and Loricrin
title_sort	force-induced strengthening of the interaction between <italic toggle="yes">staphylococcus aureus</italic> clumping factor b and loricrin
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/dd2ed11d1e2847eb979c775c523b0726
work_keys_str_mv	AT paulinevitry forceinducedstrengtheningoftheinteractionbetweenitalictoggleyesstaphylococcusaureusitalicclumpingfactorbandloricrin AT clairevalotteau forceinducedstrengtheningoftheinteractionbetweenitalictoggleyesstaphylococcusaureusitalicclumpingfactorbandloricrin AT cecilefeuillie forceinducedstrengtheningoftheinteractionbetweenitalictoggleyesstaphylococcusaureusitalicclumpingfactorbandloricrin AT simonbernard forceinducedstrengtheningoftheinteractionbetweenitalictoggleyesstaphylococcusaureusitalicclumpingfactorbandloricrin AT davidalsteens forceinducedstrengtheningoftheinteractionbetweenitalictoggleyesstaphylococcusaureusitalicclumpingfactorbandloricrin AT joanageoghegan forceinducedstrengtheningoftheinteractionbetweenitalictoggleyesstaphylococcusaureusitalicclumpingfactorbandloricrin AT yvesfdufrene forceinducedstrengtheningoftheinteractionbetweenitalictoggleyesstaphylococcusaureusitalicclumpingfactorbandloricrin
_version_	1718427309642350592

Force-Induced Strengthening of the Interaction between <italic toggle="yes">Staphylococcus aureus</italic> Clumping Factor B and Loricrin

Ejemplares similares