Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/103801
Title: Microscopy-based phenotypic profiling of infection by Staphylococcus aureus clinical isolates reveals intracellular lifestyle as a prevalent feature
Authors: Lopes, Ines Rodrigues
Alcantara, Laura Maria
Silva, Ricardo Jorge 
Josse, Jerome
Vega, Elena Pedrero
Cabrerizo, Ana Marina
Bonhomme, Melanie
Lopez, Daniel
Laurent, Frederic
Vandenesch, Francois
Mano, Miguel 
Eulálio, Ana 
Issue Date: 22-Nov-2022
Publisher: Nature
Project: info:eu-repo/grantAgreement/FCT/POR_CENTRO/PD/BD/146464/2019/PT/Deciphering host cell factors required for staphylococcus aureus infection 
info:eu-repo/grantAgreement/FCT/POR_CENTRO/PD/BD/129294/2017/PT/Identification of novel regulators of cardiac ischemia-reperfussion injury using genome-wide CRISPR/Cas9 functional screening 
info:eu-repo/grantAgreement/EC/H2020/893942/EU/Functional high-throughput analysis of the role of microRNAs in regulating Staphylococcus aureus infection 
info:eu-repo/grantAgreement/FCT/3599-PPCDT/Infect-ERA/0001/2015/PT/Intracellular Staphylococcus aureus: deciphering bacterial and cellular factors involved in host cell invasion by clinically relevant strains to define new therapeutic approaches 
info:eu-repo/grantAgreement/POCI‐01‐0145‐FEDER-007440/PT 
info:eu-repo/grantAgreement/POCI-01-0145-FEDER-029999/PT 
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04539/2020/PT 
Serial title, monograph or event: Nature Communications
Volume: 13
Issue: 1
Abstract: Staphylococcus aureus is increasingly recognized as a facultative intracellular pathogen, although the significance and pervasiveness of its intracellular lifestyle remain controversial. Here, we applied fluorescence microscopy-based infection assays and automated image analysis to profile the interaction of 191 S. aureus isolates from patients with bone/joint infections, bacteremia, and infective endocarditis, with four host cell types, at five times post-infection. This multiparametric analysis revealed that almost all isolates are internalized and that a large fraction replicate and persist within host cells, presenting distinct infection profiles in non-professional vs. professional phagocytes. Phenotypic clustering highlighted interesting sub-groups, including one comprising isolates exhibiting high intracellular replication and inducing delayed host death in vitro and in vivo. These isolates are deficient for the cysteine protease staphopain A. This study establishes S. aureus intracellular lifestyle as a prevalent feature of infection, with potential implications for the effective treatment of staphylococcal infections.
URI: https://hdl.handle.net/10316/103801
ISSN: 2041-1723
DOI: 10.1038/s41467-022-34790-9
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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