Influenza Promotes Pneumococcal Growth during Coinfection by Providing Host Sialylated Substrates as a Nutrient Source

• Published in: Cell host & microbe 2014-07, Vol.16 (1), p.55-67
• Main Authors: Siegel, Steven J., Roche, Aoife M., Weiser, Jeffrey N.
• Format: Article
• Language: English
• Subjects: Animals; Coinfection - microbiology; Coinfection - pathology; Coinfection - virology; Disease Models, Animal; Food; Lung - microbiology; Mice; Microbial Interactions; Nasopharynx - microbiology; Orthomyxoviridae - growth & development; Orthomyxoviridae Infections - complications; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; Pneumonia, Pneumococcal - complications; Pneumonia, Pneumococcal - microbiology; Pneumonia, Pneumococcal - pathology; Sialic Acids - metabolism; Streptococcus pneumoniae - growth & development; Streptococcus pneumoniae - metabolism
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2014.06.005

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. [Display omitted] •Prior influenza infection increases pneumococcal colonization, replication, and aspiration•Pneumococcal growth during coinfection depends on host-derived sialic acid utilization•Sialylated airway mucin Muc5ac is required for influenza-mediated pneumococcal growth•Viral and bacterial neuraminidases release sialic acid from host cells in vivo Pneumonia caused by Streptococcus pneumoniae commonly follows influenza infection. Siegel, et al. determine that influenza stimulates host secretion of mucins decorated with sialic acid, a carbohydrate that pneumococci can exploit. Pneumococci obtain and catabolize sialic acid from these influenza-induced host mucins, promoting pneumococcal replication, colonization, and aspiration.