Epidemiological observations and animal models have long shown synergy between influenza virus infections and bacterial infections. Influenza virus infection leads to an increase in both the susceptibility to secondary bacterial infections and the severity of the bacterial infections, primarily pneumonias caused by Streptococcus pneumoniae or Staphylococcus aureus. We show that, in addition to the widely described immune modulation and tissue-remodelling mechanisms of bacterial–viral synergy, the virus interacts directly with the bacterial surface. Similar to the recent observation of direct interactions between enteric bacteria and enteric viruses, we observed a direct interaction between influenza virus on the surface of Gram-positive, S. pneumoniae and S. aureus, and Gram-negative, Moraxella catarrhalis and non-typeable Haemophilus influenzae, bacterial colonizers and pathogens in the respiratory tract. Pre-incubation of influenza virus with bacteria, followed by the removal of unbound virus, increased bacterial adherence to respiratory epithelial cells in culture. This result was recapitulated in vivo, with higher bacterial burdens in murine tissues when infected with pneumococci pre-incubated with influenza virus versus control bacteria without virus. These observations support an additional mechanism of bacteria–influenza virus synergy at the earliest steps of pathogenesis.
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The data that support these findings are available from J. Rosch on request.
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J.W.R. is supported by the National Institutes of Allergic and Infectious Diseases (NIAID) (grant nos. 1U01AI124302 and 1RO1AI110618). S.S.-C. is supported by the NIAID (grant no. HHSN272201400006C). J.W.R. and S.S.-C. are funded by the ALSAC. Images were acquired in the Cell and Tissue Imaging Center, which is supported by St. Jude and NCI P30 CA021765.
The authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Figures 1–3 and Supplementary Video legends.
3D rendering and rotation of SIM image of mRuby2–PR8 (red) on surface of S. pneumoniae stained with AF488-WGA (green). Representative from at least 10 bacterial–viral complexes.
3D rendering and rotation, and Z-stack slices of SIM image of mRuby2–PR8 (red) on surface of S. aureus stained with AF488-WGA (green). Representative from at least 10 bacterial-viral complexes.
3D rendering and rotation of SIM image of mRuby2–PR8 (red) on surface of M. catarrhalis stained with AF488-WGA (green). Representative from at least 10 bacterial–viral complexes.
3D rendering and rotation of SIM image of mRuby2–PR8 (red) on surface of H. influenzae stained with stained with MitoTracker DeepRed (false coloured to green). Representative from at least 10 bacterial–viral complexes.