<named-content content-type="genus-species">Kingella kingae</named-content> Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing

ABSTRACT Bacterial pathogens have evolved strategies that enable them to evade neutrophil-mediated killing. The Gram-negative coccobacillus Kingella kingae is an emerging pediatric pathogen and is increasingly recognized as a common etiological agent of osteoarticular infections and bacteremia in yo...

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Autores principales:	Vanessa L. Muñoz, Eric A. Porsch, Joseph W. St. Geme
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Kingella kingae capsule exopolysaccharide immune evasion neutrophils Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/30f4401359d54c7583d0ee695ebaffd2
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spelling	oai:doaj.org-article:30f4401359d54c7583d0ee695ebaffd22021-11-15T15:55:24Z<named-content content-type="genus-species">Kingella kingae</named-content> Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing10.1128/mBio.00631-192150-7511https://doaj.org/article/30f4401359d54c7583d0ee695ebaffd22019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00631-19https://doaj.org/toc/2150-7511ABSTRACT Bacterial pathogens have evolved strategies that enable them to evade neutrophil-mediated killing. The Gram-negative coccobacillus Kingella kingae is an emerging pediatric pathogen and is increasingly recognized as a common etiological agent of osteoarticular infections and bacteremia in young children. K. kingae produces a polysaccharide capsule and an exopolysaccharide, both of which are important for protection against complement-mediated lysis and are required for full virulence in an infant rat model of infection. In this study, we examined the role of the K. kingae polysaccharide capsule and exopolysaccharide in protection against neutrophil killing. In experiments with primary human neutrophils, we found that the capsule interfered with the neutrophil oxidative burst response and prevented neutrophil binding of K. kingae but had no effect on neutrophil internalization of K. kingae. In contrast, the exopolysaccharide resisted the bactericidal effects of antimicrobial peptides and efficiently blocked neutrophil phagocytosis of K. kingae. This work demonstrates that the K. kingae polysaccharide capsule and exopolysaccharide promote evasion of neutrophil-mediated killing through distinct yet complementary mechanisms, providing additional support for the K. kingae surface polysaccharides as potential vaccine antigens. In addition, these studies highlight a novel interplay between a bacterial capsule and a bacterial exopolysaccharide and reveal new properties for a bacterial exopolysaccharide, with potential applicability to other bacterial pathogens. IMPORTANCE Kingella kingae is a Gram-negative commensal in the oropharynx and represents a leading cause of joint and bone infections in young children. The mechanisms by which K. kingae evades host innate immunity during pathogenesis of disease remain poorly understood. In this study, we established that the K. kingae polysaccharide capsule and exopolysaccharide function independently to protect K. kingae against reactive oxygen species (ROS) production, neutrophil phagocytosis, and antimicrobial peptides. These results demonstrate the intricacies of K. kingae innate immune evasion and provide valuable information that may facilitate development of a polysaccharide-based vaccine against K. kingae.Vanessa L. MuñozEric A. PorschJoseph W. St. GemeAmerican Society for MicrobiologyarticleKingella kingaecapsuleexopolysaccharideimmune evasionneutrophilsMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Kingella kingae capsule exopolysaccharide immune evasion neutrophils Microbiology QR1-502
spellingShingle	Kingella kingae capsule exopolysaccharide immune evasion neutrophils Microbiology QR1-502 Vanessa L. Muñoz Eric A. Porsch Joseph W. St. Geme <named-content content-type="genus-species">Kingella kingae</named-content> Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing
description	ABSTRACT Bacterial pathogens have evolved strategies that enable them to evade neutrophil-mediated killing. The Gram-negative coccobacillus Kingella kingae is an emerging pediatric pathogen and is increasingly recognized as a common etiological agent of osteoarticular infections and bacteremia in young children. K. kingae produces a polysaccharide capsule and an exopolysaccharide, both of which are important for protection against complement-mediated lysis and are required for full virulence in an infant rat model of infection. In this study, we examined the role of the K. kingae polysaccharide capsule and exopolysaccharide in protection against neutrophil killing. In experiments with primary human neutrophils, we found that the capsule interfered with the neutrophil oxidative burst response and prevented neutrophil binding of K. kingae but had no effect on neutrophil internalization of K. kingae. In contrast, the exopolysaccharide resisted the bactericidal effects of antimicrobial peptides and efficiently blocked neutrophil phagocytosis of K. kingae. This work demonstrates that the K. kingae polysaccharide capsule and exopolysaccharide promote evasion of neutrophil-mediated killing through distinct yet complementary mechanisms, providing additional support for the K. kingae surface polysaccharides as potential vaccine antigens. In addition, these studies highlight a novel interplay between a bacterial capsule and a bacterial exopolysaccharide and reveal new properties for a bacterial exopolysaccharide, with potential applicability to other bacterial pathogens. IMPORTANCE Kingella kingae is a Gram-negative commensal in the oropharynx and represents a leading cause of joint and bone infections in young children. The mechanisms by which K. kingae evades host innate immunity during pathogenesis of disease remain poorly understood. In this study, we established that the K. kingae polysaccharide capsule and exopolysaccharide function independently to protect K. kingae against reactive oxygen species (ROS) production, neutrophil phagocytosis, and antimicrobial peptides. These results demonstrate the intricacies of K. kingae innate immune evasion and provide valuable information that may facilitate development of a polysaccharide-based vaccine against K. kingae.
format	article
author	Vanessa L. Muñoz Eric A. Porsch Joseph W. St. Geme
author_facet	Vanessa L. Muñoz Eric A. Porsch Joseph W. St. Geme
author_sort	Vanessa L. Muñoz
title	<named-content content-type="genus-species">Kingella kingae</named-content> Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing
title_short	<named-content content-type="genus-species">Kingella kingae</named-content> Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing
title_full	<named-content content-type="genus-species">Kingella kingae</named-content> Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing
title_fullStr	<named-content content-type="genus-species">Kingella kingae</named-content> Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing
title_full_unstemmed	<named-content content-type="genus-species">Kingella kingae</named-content> Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing
title_sort	<named-content content-type="genus-species">kingella kingae</named-content> surface polysaccharides promote resistance to neutrophil phagocytosis and killing
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/30f4401359d54c7583d0ee695ebaffd2
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<named-content content-type="genus-species">Kingella kingae</named-content> Surface Polysaccharides Promote Resistance to Neutrophil Phagocytosis and Killing

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