Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus

Abstract The ability of Staphylococcus aureus to adapt and thrive in diverse host niches adds to the challenge in combating this ubiquitous pathogen. While extensive research has been pursued on the adaptive mechanisms of methicillin-resistant S. aureus (MRSA) in various infection models, a comprehe...

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Main Authors: JuOae Chang, ChaeYoung Lee, Inseo Kim, Jihyeon Kim, Ji-Hoon Kim, Taegwan Yun, David C. Hooper, Suzanne Walker, Wonsik Lee
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62292-x
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author JuOae Chang
ChaeYoung Lee
Inseo Kim
Jihyeon Kim
Ji-Hoon Kim
Taegwan Yun
David C. Hooper
Suzanne Walker
Wonsik Lee
author_facet JuOae Chang
ChaeYoung Lee
Inseo Kim
Jihyeon Kim
Ji-Hoon Kim
Taegwan Yun
David C. Hooper
Suzanne Walker
Wonsik Lee
author_sort JuOae Chang
collection DOAJ
description Abstract The ability of Staphylococcus aureus to adapt and thrive in diverse host niches adds to the challenge in combating this ubiquitous pathogen. While extensive research has been pursued on the adaptive mechanisms of methicillin-resistant S. aureus (MRSA) in various infection models, a comprehensive analysis of its fitness across different host niches is lacking. In this study, we employ transposon sequencing to analyze the adaptive strategies of MRSA in various infection niches. Our analysis encompasses a cell model that mimics an intracellular niche, human blood, which represents a major extracellular environment as well as a major intermediary route encountered by bacteria during systemic infection, and a male murine sepsis model that recapitulates intra-organ environments. Our findings reveal substantial differences in the genetic determinants essential for bacterial survival in intracellular and blood environments. Moreover, we show that each organ imposes unique growth constraints, thus fostering heterogeneity within the mutant population that can enter and survive in each organ of the mouse. By comparing genes important for survival across all examined host environments, we identify 27 core genes that represent potential therapeutic targets for treating S. aureus infections. Additionally, our findings aid in understanding how bacteria adapt to diverse host environments.
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issn 2041-1723
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spelling doaj-art-2d6d65df48464fcfb8a81d3952506e802025-08-20T03:46:23ZengNature PortfolioNature Communications2041-17232025-07-0116111410.1038/s41467-025-62292-xEnvironmental cues in different host niches shape the survival fitness of Staphylococcus aureusJuOae Chang0ChaeYoung Lee1Inseo Kim2Jihyeon Kim3Ji-Hoon Kim4Taegwan Yun5David C. Hooper6Suzanne Walker7Wonsik Lee8School of Pharmacy, Sungkyunkwan UniversitySchool of Pharmacy, Sungkyunkwan UniversitySchool of Pharmacy, Sungkyunkwan UniversitySchool of Pharmacy, Sungkyunkwan UniversitySchool of Pharmacy, Sungkyunkwan UniversitySchool of Pharmacy, Sungkyunkwan UniversityDivision of Infectious Diseases, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Microbiology, Harvard Medical SchoolSchool of Pharmacy, Sungkyunkwan UniversityAbstract The ability of Staphylococcus aureus to adapt and thrive in diverse host niches adds to the challenge in combating this ubiquitous pathogen. While extensive research has been pursued on the adaptive mechanisms of methicillin-resistant S. aureus (MRSA) in various infection models, a comprehensive analysis of its fitness across different host niches is lacking. In this study, we employ transposon sequencing to analyze the adaptive strategies of MRSA in various infection niches. Our analysis encompasses a cell model that mimics an intracellular niche, human blood, which represents a major extracellular environment as well as a major intermediary route encountered by bacteria during systemic infection, and a male murine sepsis model that recapitulates intra-organ environments. Our findings reveal substantial differences in the genetic determinants essential for bacterial survival in intracellular and blood environments. Moreover, we show that each organ imposes unique growth constraints, thus fostering heterogeneity within the mutant population that can enter and survive in each organ of the mouse. By comparing genes important for survival across all examined host environments, we identify 27 core genes that represent potential therapeutic targets for treating S. aureus infections. Additionally, our findings aid in understanding how bacteria adapt to diverse host environments.https://doi.org/10.1038/s41467-025-62292-x
spellingShingle JuOae Chang
ChaeYoung Lee
Inseo Kim
Jihyeon Kim
Ji-Hoon Kim
Taegwan Yun
David C. Hooper
Suzanne Walker
Wonsik Lee
Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus
Nature Communications
title Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus
title_full Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus
title_fullStr Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus
title_full_unstemmed Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus
title_short Environmental cues in different host niches shape the survival fitness of Staphylococcus aureus
title_sort environmental cues in different host niches shape the survival fitness of staphylococcus aureus
url https://doi.org/10.1038/s41467-025-62292-x
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