title: Methylthioadenosine/S-adenosylhomocysteine nucleosidase (Pfs) of Staphylococcus aureus is essential for the virulence independent of LuxS/AI-2 system.
abstract: Staphylococcus aureus is a major cause of infectious morbidity and mortality in both community and hospital settings. The bacterium continues to cause diverse invasive, life-threatening infections, such as pneumonia, endocarditis, and septicemia. Methylthioadenosine/S-adenosylhomocysteine nucleosidase (Pfs) is predicted to be an important enzyme involved in methylation reactions, polyamine synthesis, vitamin synthesis, and quorum sensing pathways. For the first time, we demonstrate that Pfs is essential for the virulence of S. aureus. The pfs mutant strain, as compared to the isogenic wild type, displayed a decreased production of extracellular proteases, which was correlated with a dramatic decrease in the expression of the sspABC operon and a moderate decrease of aur expression. The mouse model of sepsis and subcutaneous abscesses indicated that the pfs mutant strain displayed highly impaired virulence compared to the isogenic wild type. The decreased virulence of the pfs mutant strain is in correspondence with its decreased proliferation in vivo, indicated with a real-time analysis in the transparent system of zebrafish embryos. These phenotypes of the pfs mutant strain are LuxS/AI-2 independent despite the essential role pfs plays in AI-2 production. Our data suggest that Pfs is a potential novel target for anti-infection therapy.
authors.affiliation: Hefei National Laboratory for Physical Sciences, Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bao
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Li
authors.forename: Qiu
authors.initials: Q
authors.lastname: Jiang
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.forename: Ting
authors.initials: T
authors.lastname: Xue
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.forename: Baolin
authors.initials: B
authors.lastname: Sun
mesh_terms: D000038:Abscess / Q000382:microbiology / Q000473:pathology; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D013437:Carbon-Sulfur Lyases / Q000378:metabolism*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism*; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000382:microbiology / Q000473:pathology; D013207:Staphylococcal Skin Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D001426:Bacterial Proteins; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D037521:Virulence Factors; D006714:Homoserine; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase; D009699:N-Glycosyl Hydrolases; C019606:adenosylhomocysteine nucleosidase; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria