Neuraminidase A-Exposed Galactose Promotes Streptococcus pneumoniae Biofilm Formation during Colonization

  • Krystle A. Blanchette
    Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  • Anukul T. Shenoy
    Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  • Jeffrey Milner
    Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  • Ryan P. Gilley
    Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  • Erin McClure
    Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
  • Cecilia A. Hinojosa
    Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  • Nikhil Kumar
    Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
  • Sean C. Daugherty
    Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
  • Luke J. Tallon
    Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
  • Sandra Ott
    Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
  • Samantha J. King
    Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
  • Daniela M. Ferreira
    Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
  • Stephen B. Gordon
    Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
  • Hervé Tettelin
    Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
  • Carlos J. Orihuela
    Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

説明

<jats:title>ABSTRACT</jats:title> <jats:p> <jats:named-content content-type="genus-species">Streptococcus pneumoniae</jats:named-content> is an opportunistic pathogen that colonizes the nasopharynx. Herein we show that carbon availability is distinct between the nasopharynx and bloodstream of adult humans: glucose is absent from the nasopharynx, whereas galactose is abundant. We demonstrate that pneumococcal neuraminidase A (NanA), which cleaves terminal sialic acid residues from host glycoproteins, exposed galactose on the surface of septal epithelial cells, thereby increasing its availability during colonization. We observed that <jats:named-content content-type="genus-species">S. pneumoniae</jats:named-content> mutants deficient in NanA and β-galactosidase A (BgaA) failed to form biofilms <jats:italic>in vivo</jats:italic> despite normal biofilm-forming abilities <jats:italic>in vitro</jats:italic> . Subsequently, we observed that glucose, sucrose, and fructose were inhibitory for biofilm formation, whereas galactose, lactose, and low concentrations of sialic acid were permissive. Together these findings suggested that the genes involved in biofilm formation were under some form of carbon catabolite repression (CCR), a regulatory network in which genes involved in the uptake and metabolism of less-preferred sugars are silenced during growth with preferred sugars. Supporting this notion, we observed that a mutant deficient in pyruvate oxidase, which converts pyruvate to acetyl-phosphate under non-CCR-inducing growth conditions, was unable to form biofilms. Subsequent comparative transcriptome sequencing (RNA-seq) analyses of planktonic and biofilm-grown pneumococci showed that metabolic pathways involving the conversion of pyruvate to acetyl-phosphate and subsequently leading to fatty acid biosynthesis were consistently upregulated during diverse biofilm growth conditions. We conclude that carbon availability in the nasopharynx impacts pneumococcal biofilm formation <jats:italic>in vivo</jats:italic> . Additionally, biofilm formation involves metabolic pathways not previously appreciated to play an important role. </jats:p>

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