Direct interactions with influenza promote bacterial adherence during respiratory infections

Nat Microbiol. 2019 Aug;4(8):1328-1336. doi: 10.1038/s41564-019-0447-0. Epub 2019 May 20.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • A549 Cells
  • Animals
  • Bacteria
  • Bacterial Adhesion / physiology*
  • Bacterial Infections / complications
  • Bacterial Infections / microbiology
  • Bacterial Infections / virology
  • Coinfection*
  • Disease Models, Animal
  • Female
  • Humans
  • Influenza, Human
  • Mice
  • Mice, Inbred BALB C
  • Microbial Interactions / physiology*
  • Orthomyxoviridae Infections / complications
  • Respiratory Tract Infections / complications
  • Respiratory Tract Infections / microbiology*
  • Respiratory Tract Infections / virology*
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / microbiology*
  • Staphylococcal Infections / virology*
  • Staphylococcus aureus
  • Streptococcus pneumoniae