Systematic identification of bacterial factors driving Staphylococcus aureus intracellular lifestyle in non-professional phagocytes
Year: 2025
Type: article
Abstract: Staphylococcus aureus is a major human pathogen responsible for severe infections. While traditionally described as extracellular, increasing evidence establishes S. aureus as a facultative intracellular pathogen. Intracellularity contributes to immune evasion, dissemination, and antibiotic failure. To identify bacterial factors critical for S. aureus invasion, intracellular replication, persistence, and host cytotoxicity, we screened a comprehensive collection of 1920 S. aureus mutants (Nebraska Transposon Mutant Library) in epithelial cells across five timepoints (0.5 to 48 hours post-infection). We identified 73 bacterial factors strongly modulating S. aureus intracellularity, including mutants displaying multiple phenotypes. Most of these factors have not been linked to intracellular lifestyle. Among these, we characterized the nicotinamidase PncA as a novel regulator of the agr system via redox state modulation, strongly impacting virulence. This study provides a systematic analysis of S. aureus factors critical for intracellular lifestyle, with implications for the development of antimicrobial strategies targeting this resilient bacterial population.
Source: Nature Communications
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Imperial College London, European Commission, Bundesministerium für Bildung und Forschung, Universidade de Coimbra, Hospices Civils de Lyon, Agência Nacional de Inovação, Julius-Maximilians-Universität Würzburg, Programa Operacional Regional do Centro, Fundação para a Ciência e a Tecnologia, European Regional Development Fund
Awards: G1167214205, G1297482482, G137578274, G1577006909, G1578237752, G1893869327, G1919449872, Centro de Inovação em Biomedicina e Biotecnologia, G2120309575, G2198755072, G37688986, G3891694003, Staphylococcus aureus intracelular: identificação de factores bacterianos e celulares envolvidos na invasão do hospedeiro por estirpes clinicamente relevantes para definição de novas abordagens terapêuticas, G4705738886, G4810541173, G491858407, G5642561709, Centro de Inovação em Biomedicina e Biotecnologia, G6725904030, Centro de Inovação em Biomedicina e Biotecnologia - Laboratório Associado, G7331859268, G781477293, G810402943
OpenAlex ID: W4417185553