title: The Spl Serine Proteases ModulateStaphylococcus aureusProtein Production and Virulence in a Rabbit Model of Pneumonia.
abstract: The Spl proteases are a group of six serine proteases that are encoded on the νSaβ pathogenicity island and are unique toStaphylococcus aureus. Despite their interesting biochemistry, their biological substrates and functions in virulence have been difficult to elucidate. We found that ansploperon mutant of the community-associated methicillin-resistantS. aureusUSA300 strain LAC induced localized lung damage in a rabbit model of pneumonia, characterized by bronchopneumonia observed histologically. Disease in the mutant-infected rabbits was restricted in distribution compared to that in wild-type USA300-infected rabbits. We also found that SplA is able to cleave the mucin 16 glycoprotein from the surface of the CalU-3 lung cell line, suggesting a possible mechanism for wild-type USA300 spreading pneumonia to both lungs. Investigation of the secreted and surface proteomes of wild-type USA300 and thesplmutant revealed multiple alterations in metabolic proteins and virulence factors. This study demonstrates that the Spls modulateS. aureusphysiology and virulence, identifies a human target of SplA, and suggests potentialS. aureustargets of the Spl proteases.IMPORTANCEStaphylococcus aureusis a versatile human pathogen that produces an array of virulence factors, including several proteases. Of these, six proteases called the Spls are the least characterized. Previous evidence suggests that the Spls are expressed during human infection; however, their function is unknown. Our study shows that the Spls are required forS. aureusto cause disseminated lung damage during pneumonia. Further, we present the first example of a human protein cut by an Spl protease. Although the Spls were predicted not to cut staphylococcal proteins, we also show that ansplmutant has altered abundance of both secreted and surface-associated proteins. This work provides novel insight into the function of Spls during infection and their potential ability to degrade both staphylococcal and human proteins.
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Alexandra E
authors.identifier: 0000-0003-4743-0406
authors.initials: AE
authors.lastname: Paharik
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Wilmara
authors.initials: W
authors.lastname: Salgado-Pabon
authors.affiliation: Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Meyerholz
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: White
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Schlievert
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Horswill
keywords: Spl; Staphylococcus aureus; mucin; pneumonia; proteases; virulence factors