Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that the <italic toggle="yes">dlt</italic> Locus Promotes Inflammation and Transmission

ABSTRACT Host-to-host transmission is a necessary but poorly understood aspect of microbial pathogenesis. Herein, we screened a genomic library of mutants of the leading respiratory pathogen Streptococcus pneumoniae generated by mariner transposon mutagenesis (Tn-Seq) to identify genes contributing...

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Autores principales:	M. Ammar Zafar, Alexandria J. Hammond, Shigeto Hamaguchi, Weisheng Wu, Masamitsu Kono, Lili Zhao, Jeffrey N. Weiser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	bacterial transmission Streptococcus pneumoniae host-pathogen interactions inflammation transposon mutagenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b6c89ed1bffe4b75a6bd6fe0635854ad
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spelling	oai:doaj.org-article:b6c89ed1bffe4b75a6bd6fe0635854ad2021-11-15T15:55:25ZIdentification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that the <italic toggle="yes">dlt</italic> Locus Promotes Inflammation and Transmission10.1128/mBio.01032-192150-7511https://doaj.org/article/b6c89ed1bffe4b75a6bd6fe0635854ad2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01032-19https://doaj.org/toc/2150-7511ABSTRACT Host-to-host transmission is a necessary but poorly understood aspect of microbial pathogenesis. Herein, we screened a genomic library of mutants of the leading respiratory pathogen Streptococcus pneumoniae generated by mariner transposon mutagenesis (Tn-Seq) to identify genes contributing to its exit or shedding from the upper respiratory tract (URT), the limiting step in the organism’s transmission in an infant mouse model. Our analysis focused on genes affecting the bacterial surface that directly impact interactions with the host. Among the multiple factors identified was the dlt locus, which adds d-alanine onto lipoteichoic acids (LTA) and thereby increases Toll-like receptor 2-mediated inflammation and resistance to antimicrobial peptides. The more robust proinflammatory response in the presence of d-alanylation promotes secretions that facilitate pneumococcal shedding and allows for transmission. Expression of the dlt locus is controlled by the CiaRH system, which senses cell wall stress in response to antimicrobial activity, including in response to lysozyme, the most abundant antimicrobial along the URT mucosa. Accordingly, in a lysM−/− host, there was no longer an effect of the dlt locus on pneumococcal shedding. Thus, our findings demonstrate how a pathogen senses the URT milieu and then modifies its surface characteristics to take advantage of the host response for transit to another host. IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is a common cause of respiratory tract and invasive infection. The overall effectiveness of immunization with the organism’s capsular polysaccharide depends on its ability to block colonization of the upper respiratory tract and thereby prevent host-to-host transmission. Because of the limited coverage of current pneumococcal vaccines, we carried out an unbiased in vivo transposon mutagenesis screen to identify pneumococcal factors other than its capsular polysaccharide that affect transmission. One such candidate was expressed by the dlt locus, previously shown to add d-alanine onto the pneumococcal lipoteichoic acid present on the bacterial cell surface. This modification protects against host antimicrobials and augments host inflammatory responses. The latter increases secretions and bacterial shedding from the upper respiratory tract to allow for transmission. Thus, this study provides insight into a mechanism employed by the pneumococcus to successfully transit from one host to another.M. Ammar ZafarAlexandria J. HammondShigeto HamaguchiWeisheng WuMasamitsu KonoLili ZhaoJeffrey N. WeiserAmerican Society for Microbiologyarticlebacterial transmissionStreptococcus pneumoniaehost-pathogen interactionsinflammationtransposon mutagenesisMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacterial transmission Streptococcus pneumoniae host-pathogen interactions inflammation transposon mutagenesis Microbiology QR1-502
spellingShingle	bacterial transmission Streptococcus pneumoniae host-pathogen interactions inflammation transposon mutagenesis Microbiology QR1-502 M. Ammar Zafar Alexandria J. Hammond Shigeto Hamaguchi Weisheng Wu Masamitsu Kono Lili Zhao Jeffrey N. Weiser Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that the <italic toggle="yes">dlt</italic> Locus Promotes Inflammation and Transmission
description	ABSTRACT Host-to-host transmission is a necessary but poorly understood aspect of microbial pathogenesis. Herein, we screened a genomic library of mutants of the leading respiratory pathogen Streptococcus pneumoniae generated by mariner transposon mutagenesis (Tn-Seq) to identify genes contributing to its exit or shedding from the upper respiratory tract (URT), the limiting step in the organism’s transmission in an infant mouse model. Our analysis focused on genes affecting the bacterial surface that directly impact interactions with the host. Among the multiple factors identified was the dlt locus, which adds d-alanine onto lipoteichoic acids (LTA) and thereby increases Toll-like receptor 2-mediated inflammation and resistance to antimicrobial peptides. The more robust proinflammatory response in the presence of d-alanylation promotes secretions that facilitate pneumococcal shedding and allows for transmission. Expression of the dlt locus is controlled by the CiaRH system, which senses cell wall stress in response to antimicrobial activity, including in response to lysozyme, the most abundant antimicrobial along the URT mucosa. Accordingly, in a lysM−/− host, there was no longer an effect of the dlt locus on pneumococcal shedding. Thus, our findings demonstrate how a pathogen senses the URT milieu and then modifies its surface characteristics to take advantage of the host response for transit to another host. IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is a common cause of respiratory tract and invasive infection. The overall effectiveness of immunization with the organism’s capsular polysaccharide depends on its ability to block colonization of the upper respiratory tract and thereby prevent host-to-host transmission. Because of the limited coverage of current pneumococcal vaccines, we carried out an unbiased in vivo transposon mutagenesis screen to identify pneumococcal factors other than its capsular polysaccharide that affect transmission. One such candidate was expressed by the dlt locus, previously shown to add d-alanine onto the pneumococcal lipoteichoic acid present on the bacterial cell surface. This modification protects against host antimicrobials and augments host inflammatory responses. The latter increases secretions and bacterial shedding from the upper respiratory tract to allow for transmission. Thus, this study provides insight into a mechanism employed by the pneumococcus to successfully transit from one host to another.
format	article
author	M. Ammar Zafar Alexandria J. Hammond Shigeto Hamaguchi Weisheng Wu Masamitsu Kono Lili Zhao Jeffrey N. Weiser
author_facet	M. Ammar Zafar Alexandria J. Hammond Shigeto Hamaguchi Weisheng Wu Masamitsu Kono Lili Zhao Jeffrey N. Weiser
author_sort	M. Ammar Zafar
title	Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that the <italic toggle="yes">dlt</italic> Locus Promotes Inflammation and Transmission
title_short	Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that the <italic toggle="yes">dlt</italic> Locus Promotes Inflammation and Transmission
title_full	Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that the <italic toggle="yes">dlt</italic> Locus Promotes Inflammation and Transmission
title_fullStr	Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that the <italic toggle="yes">dlt</italic> Locus Promotes Inflammation and Transmission
title_full_unstemmed	Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that the <italic toggle="yes">dlt</italic> Locus Promotes Inflammation and Transmission
title_sort	identification of pneumococcal factors affecting pneumococcal shedding shows that the <italic toggle="yes">dlt</italic> locus promotes inflammation and transmission
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b6c89ed1bffe4b75a6bd6fe0635854ad
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Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that the <italic toggle="yes">dlt</italic> Locus Promotes Inflammation and Transmission

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