Identification of Key Determinants of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Vaginal Colonization

ABSTRACT Staphylococcus aureus is an important pathogen responsible for nosocomial and community-acquired infections in humans, and methicillin-resistant S. aureus (MRSA) infections have continued to increase despite widespread preventative measures. S. aureus can colonize the female vaginal tract,...

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Autores principales:	Liwen Deng, Katrin Schilcher, Lindsey R. Burcham, Jakub M. Kwiecinski, Paige M. Johnson, Steven R. Head, David E. Heinrichs, Alexander R. Horswill, Kelly S. Doran
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	MRSA RNA sequencing Staphylococcus aureus fibrinogen iron vaginal colonization Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2a15eb7826e34c0287e69b7d39b3d578
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spelling	oai:doaj.org-article:2a15eb7826e34c0287e69b7d39b3d5782021-11-15T15:54:46ZIdentification of Key Determinants of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Vaginal Colonization10.1128/mBio.02321-192150-7511https://doaj.org/article/2a15eb7826e34c0287e69b7d39b3d5782019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02321-19https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus is an important pathogen responsible for nosocomial and community-acquired infections in humans, and methicillin-resistant S. aureus (MRSA) infections have continued to increase despite widespread preventative measures. S. aureus can colonize the female vaginal tract, and reports have suggested an increase in MRSA infections in pregnant and postpartum women as well as outbreaks in newborn nurseries. Currently, little is known about specific factors that promote MRSA vaginal colonization and subsequent infection. To study S. aureus colonization of the female reproductive tract in a mammalian system, we developed a mouse model of S. aureus vaginal carriage and demonstrated that both hospital-associated and community-associated MRSA isolates can colonize the murine vaginal tract. Immunohistochemical analysis revealed an increase in neutrophils in the vaginal lumen during MRSA colonization. Additionally, we observed that a mutant lacking fibrinogen binding adhesins exhibited decreased persistence within the mouse vagina. To further identify novel factors that promote vaginal colonization, we performed RNA sequencing to determine the transcriptome of MRSA growing in vivo during vaginal carriage at 5 h, 1 day, and 3 days postinoculation. Over 25% of the bacterial genes were differentially regulated at all time points during colonization compared to laboratory cultures. The most highly induced genes were those involved in iron acquisition, including the Isd system and siderophore transport systems. Mutants deficient in these pathways did not persist as well during in vivo colonization. These results reveal that fibrinogen binding and the capacity to overcome host nutritional limitation are important determinants of MRSA vaginal colonization. IMPORTANCE Staphylococcus aureus is an opportunistic pathogen able to cause a wide variety of infections in humans. Recent reports have suggested an increasing prevalence of MRSA in pregnant and postpartum women, coinciding with the increased incidence of MRSA infections in neonatal intensive care units (NICUs) and newborn nurseries. Vertical transmission from mothers to infants at delivery is a likely route of MRSA acquisition by the newborn; however, essentially nothing is known about host and bacterial factors that influence MRSA carriage in the vagina. Here, we established a mouse model of vaginal colonization and observed that multiple MRSA strains can persist in the vaginal tract. Additionally, we determined that MRSA interactions with fibrinogen and iron uptake can promote vaginal persistence. This study is the first to identify molecular mechanisms which govern vaginal colonization by MRSA, the critical initial step preceding infection and neonatal transmission.Liwen DengKatrin SchilcherLindsey R. BurchamJakub M. KwiecinskiPaige M. JohnsonSteven R. HeadDavid E. HeinrichsAlexander R. HorswillKelly S. DoranAmerican Society for MicrobiologyarticleMRSARNA sequencingStaphylococcus aureusfibrinogenironvaginal colonizationMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	MRSA RNA sequencing Staphylococcus aureus fibrinogen iron vaginal colonization Microbiology QR1-502
spellingShingle	MRSA RNA sequencing Staphylococcus aureus fibrinogen iron vaginal colonization Microbiology QR1-502 Liwen Deng Katrin Schilcher Lindsey R. Burcham Jakub M. Kwiecinski Paige M. Johnson Steven R. Head David E. Heinrichs Alexander R. Horswill Kelly S. Doran Identification of Key Determinants of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Vaginal Colonization
description	ABSTRACT Staphylococcus aureus is an important pathogen responsible for nosocomial and community-acquired infections in humans, and methicillin-resistant S. aureus (MRSA) infections have continued to increase despite widespread preventative measures. S. aureus can colonize the female vaginal tract, and reports have suggested an increase in MRSA infections in pregnant and postpartum women as well as outbreaks in newborn nurseries. Currently, little is known about specific factors that promote MRSA vaginal colonization and subsequent infection. To study S. aureus colonization of the female reproductive tract in a mammalian system, we developed a mouse model of S. aureus vaginal carriage and demonstrated that both hospital-associated and community-associated MRSA isolates can colonize the murine vaginal tract. Immunohistochemical analysis revealed an increase in neutrophils in the vaginal lumen during MRSA colonization. Additionally, we observed that a mutant lacking fibrinogen binding adhesins exhibited decreased persistence within the mouse vagina. To further identify novel factors that promote vaginal colonization, we performed RNA sequencing to determine the transcriptome of MRSA growing in vivo during vaginal carriage at 5 h, 1 day, and 3 days postinoculation. Over 25% of the bacterial genes were differentially regulated at all time points during colonization compared to laboratory cultures. The most highly induced genes were those involved in iron acquisition, including the Isd system and siderophore transport systems. Mutants deficient in these pathways did not persist as well during in vivo colonization. These results reveal that fibrinogen binding and the capacity to overcome host nutritional limitation are important determinants of MRSA vaginal colonization. IMPORTANCE Staphylococcus aureus is an opportunistic pathogen able to cause a wide variety of infections in humans. Recent reports have suggested an increasing prevalence of MRSA in pregnant and postpartum women, coinciding with the increased incidence of MRSA infections in neonatal intensive care units (NICUs) and newborn nurseries. Vertical transmission from mothers to infants at delivery is a likely route of MRSA acquisition by the newborn; however, essentially nothing is known about host and bacterial factors that influence MRSA carriage in the vagina. Here, we established a mouse model of vaginal colonization and observed that multiple MRSA strains can persist in the vaginal tract. Additionally, we determined that MRSA interactions with fibrinogen and iron uptake can promote vaginal persistence. This study is the first to identify molecular mechanisms which govern vaginal colonization by MRSA, the critical initial step preceding infection and neonatal transmission.
format	article
author	Liwen Deng Katrin Schilcher Lindsey R. Burcham Jakub M. Kwiecinski Paige M. Johnson Steven R. Head David E. Heinrichs Alexander R. Horswill Kelly S. Doran
author_facet	Liwen Deng Katrin Schilcher Lindsey R. Burcham Jakub M. Kwiecinski Paige M. Johnson Steven R. Head David E. Heinrichs Alexander R. Horswill Kelly S. Doran
author_sort	Liwen Deng
title	Identification of Key Determinants of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Vaginal Colonization
title_short	Identification of Key Determinants of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Vaginal Colonization
title_full	Identification of Key Determinants of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Vaginal Colonization
title_fullStr	Identification of Key Determinants of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Vaginal Colonization
title_full_unstemmed	Identification of Key Determinants of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Vaginal Colonization
title_sort	identification of key determinants of <named-content content-type="genus-species">staphylococcus aureus</named-content> vaginal colonization
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/2a15eb7826e34c0287e69b7d39b3d578
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Identification of Key Determinants of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Vaginal Colonization

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