title: Using Quantitative Spectrometry to Understand the Influence of Genetics and Nutritional Perturbations On the Virulence Potential ofStaphylococcus aureus.
abstract: Staphylococcus aureus(Sa) is the leading cause of a variety of bacterial infections ranging from superficial skin infections to invasive and life threatening diseases such as septic bacteremia, necrotizing pneumonia, and endocarditis. The success ofSaas a human pathogen is contributed to its ability to adapt to different environments by changing expression, production, or secretion of virulence factors. AlthoughSaimmune evasion is well-studied, the regulation of virulence factors under different nutrient and growth conditions is still not well understood. Here, we used label-free quantitative mass spectrometry to quantify and compare theSaexoproteins (i.e.exoproteomes) of master regulator mutants or established reference strains. Different environmental conditions were addressed by growing the bacteria in rich or minimal media at different phases of growth. We observed clear differences in the composition of the exoproteomes depending on the genetic background or growth conditions. The relative abundance of cytotoxins determined in our study correlated well with differences in cytotoxicity measured by lysis of human neutrophils. Our findings demonstrate that label-free quantitative mass spectrometry is a versatile tool for predicting the virulence of bacterial strains and highlights the importance of the experimental design forin vitrostudies. Furthermore, the results indicate that label-free proteomics can be used to cluster isolates into groups with similar virulence properties, highlighting the power of label-free quantitative mass spectrometry to distinguishSastrains.
authors.affiliation: From the ‡Proteomics Laboratory.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Chapman
authors.affiliation: §Department of Microbiology.
authors.forename: Divya
authors.initials: D
authors.lastname: Balasubramanian
authors.affiliation: §Department of Microbiology.
authors.forename: Kayan
authors.initials: K
authors.lastname: Tam
authors.affiliation: ¶Biomedical Hosting LLC.
authors.forename: Manor
authors.initials: M
authors.lastname: Askenazi
authors.affiliation: §Department of Microbiology.|‖Department of Medicine.
authors.forename: Richard
authors.initials: R
authors.lastname: Copin
authors.affiliation: §Department of Microbiology.|‖Department of Medicine.
authors.forename: Bo
authors.initials: B
authors.lastname: Shopsin
authors.affiliation: §Department of Microbiology, Beatrix.Ueberheide@nyumc.org Victor.Torres@nyumc.org.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Torres
authors.affiliation: From the ‡Proteomics Laboratory, Beatrix.Ueberheide@nyumc.org Victor.Torres@nyumc.org.|**Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016.
authors.forename: Beatrix M
authors.initials: BM
authors.lastname: Ueberheide
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003603:Cytotoxins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005838:Genotype; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009504:Neutrophils / Q000382:microbiology*; D040901:Proteomics / Q000379:methods; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D003603:Cytotoxins; D037521:Virulence Factors