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Anatomical Site-Specific Carbohydrate Availability Impacts Streptococcus pneumoniae Virulence and Fitness during Colonization and Disease.
Im, Hansol; Kruckow, Katherine L; D'Mello, Adonis; Ganaie, Feroze; Martinez, Eriel; Luck, Jennifer N; Cichos, Kyle H; Riegler, Ashleigh N; Song, Xiuhong; Ghanem, Elie; Saad, Jamil S; Nahm, Moon H; Tettelin, Hervé; Orihuela, Carlos J.
Afiliação
  • Im H; Department of Microbiology, School of Medicine, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Kruckow KL; Department of Microbiology, School of Medicine, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • D'Mello A; Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Ganaie F; Department of Medicine, Division of Pulmonary/Allergy/Critical Care, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Martinez E; Department of Microbiology, School of Medicine, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Luck JN; Department of Microbiology, School of Medicine, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Cichos KH; Department of Orthopaedic Surgery Arthroplasty Section, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Riegler AN; Department of Microbiology, School of Medicine, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Song X; Department of Microbiology, School of Medicine, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Ghanem E; Department of Orthopaedic Surgery Arthroplasty Section, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Saad JS; Department of Microbiology, School of Medicine, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Nahm MH; Department of Medicine, Division of Pulmonary/Allergy/Critical Care, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
  • Tettelin H; Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Orihuela CJ; Department of Microbiology, School of Medicine, The University of Alabama at Birminghamgrid.265892.2, Birmingham, Alabama, USA.
Infect Immun ; 90(1): e0045121, 2022 01 25.
Article em En | MEDLINE | ID: mdl-34748366
Streptococcus pneumoniae colonizes the nasopharynx asymptomatically but can also cause severe life-threatening disease. Importantly, stark differences in carbohydrate availability exist between the nasopharynx and invasive disease sites, such as the bloodstream, which most likely impact S. pneumoniae's behavior. Herein, using chemically defined medium (CDM) supplemented with physiological levels of carbohydrates, we examined how anatomical site-specific carbohydrate availability impacted S. pneumoniae physiology and virulence. S. pneumoniae cells grown in CDM modeling the nasopharynx (CDM-N) had reduced metabolic activity and a lower growth rate, demonstrated mixed acid fermentation with marked H2O2 production, and were in a carbon-catabolite repression (CCR)-derepressed state versus S. pneumoniae cells grown in CDM modeling blood (CDM-B). Using transcriptome sequencing (RNA-seq), we determined the transcriptome for the S. pneumoniae wild-type (WT) strain and its isogenic CCR-deficient mutant in CDM-N and CDM-B. Genes with altered expression as a result of changes in carbohydrate availability or catabolite control protein deficiency, respectively, were primarily involved in carbohydrate metabolism, but also encoded established virulence determinants, such as polysaccharide capsule and surface adhesins. We confirmed that anatomical site-specific carbohydrate availability directly influenced established S. pneumoniae virulence traits. S. pneumoniae cells grown in CDM-B formed shorter chains, produced more capsule, were less adhesive, and were more resistant to macrophage killing in an opsonophagocytosis assay. Moreover, growth of S. pneumoniae in CDM-N or CDM-B prior to the challenge of mice impacted relative fitness in a colonization model and invasive disease model, respectively. Thus, anatomical site-specific carbohydrate availability alters S. pneumoniae physiology and virulence, in turn promoting anatomical site-specific fitness.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções Pneumocócicas / Streptococcus pneumoniae / Adaptação Fisiológica / Metabolismo dos Carboidratos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Infect Immun Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções Pneumocócicas / Streptococcus pneumoniae / Adaptação Fisiológica / Metabolismo dos Carboidratos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Infect Immun Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos