title: Polyamine transporter in Streptococcus pneumoniae is essential for evading early innate immune responses in pneumococcal pneumonia.
abstract: Streptococcus pneumoniae is the most common bacterial etiology of pneumococcal pneumonia in adults worldwide. Genomic plasticity, antibiotic resistance and extreme capsular antigenic variation complicates the design of effective therapeutic strategies. Polyamines are ubiquitous small cationic molecules necessary for full expression of pneumococcal virulence. Polyamine transport system is an attractive therapeutic target as it is highly conserved across pneumococcal serotypes. In this study, we compared an isogenic deletion strain of S. pneumoniae TIGR4 in polyamine transport operon (ΔpotABCD) with the wild type in a mouse model of pneumococcal pneumonia. Our results show that the wild type persists in mouse lung 24 h post infection while the mutant strain is cleared by host defense mechanisms. We show that intact potABCD is required for survival in the host by providing resistance to neutrophil killing. Comparative proteomics analysis of murine lungs infected with wild type and ΔpotABCD pneumococci identified expression of proteins that could confer protection to wild type strain and help establish infection. We identified ERM complex, PGLYRP1, PTPRC/CD45 and POSTN as new players in the pathogenesis of pneumococcal pneumonia. Additionally, we found that deficiency of polyamine transport leads to up regulation of the polyamine synthesis genes speE and cad in vitro.
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
authors.forename: Aswathy N
authors.initials: AN
authors.lastname: Rai
authors.affiliation: Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Thornton
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
authors.forename: John
authors.initials: J
authors.lastname: Stokes
authors.affiliation: Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Imran
authors.initials: I
authors.lastname: Sunesara
authors.affiliation: Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Swiatlo
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
authors.forename: Bindu
authors.initials: B
authors.lastname: Nanduri
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D057131:Immune Evasion; D007113:Immunity, Innate; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D009876:Operon; D011018:Pneumonia, Pneumococcal / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D011073:Polyamines / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; C113582:Pglyrp1 protein, mouse; D011073:Polyamines; C082838:Postn protein, mouse; D014157:Transcription Factors; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse