title: Influenza promotes pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source.
abstract: Much of the mortality attributed to influenza virus is due to secondary bacterial pneumonia, particularly from Streptococcus pneumoniae. However, mechanisms underlying this coinfection are incompletely understood. We find that prior influenza infection enhances pneumococcal colonization of the murine nasopharynx, which in turn promotes bacterial spread to the lungs. Influenza accelerates bacterial replication in vivo, and sialic acid, a major component of airway glycoconjugates, is identified as the host-derived metabolite that stimulates pneumococcal proliferation. Influenza infection increases sialic acid and sialylated mucin availability and enhances desialylation of host glycoconjugates. Pneumococcal genes for sialic acid catabolism are required for influenza to promote bacterial growth. Decreasing sialic acid availability in vivo by genetic deletion of the major airway mucin Muc5ac or mucolytic treatment limits influenza-induced pneumococcal replication. Our findings suggest that higher rates of disease during coinfection could stem from influenza-provided sialic acid, which increases pneumococcal proliferation, colonization, and aspiration.
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Siegel
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Roche
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: weiser@mail.med.upenn.edu.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
mesh_terms: D000818:Animals; D060085:Coinfection / Q000382:microbiology / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D005502:Food; D008168:Lung / Q000382:microbiology; D051379:Mice; D056265:Microbial Interactions; D009305:Nasopharynx / Q000382:microbiology; D009975:Orthomyxoviridae / Q000254:growth & development*; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D012794:Sialic Acids / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000254:growth & development* / Q000378:metabolism
chemical_list: D012794:Sialic Acids