ModA2 phasevarion switching in nontypeable haemophilus influenzae increases the severity of experimental otitis media

Kenneth L Brockman, Joseph A Jurcisek, John M Atack, Yogitha N. Srikhanta, Michael P Jennings, Lauren O Bakaletz

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

Several human-adapted bacterial pathogens use a phasevarion (ie, a phase-variable regulon) to rapidly and reversibly regulate the expression of many genes, which include known virulence factors, yet the influence of phasevarion-mediated regulation in pathogenesis remains poorly understood. Here we examine the impact of the nontypeable Haemophilus influenzae (NTHI) ModA2 phasevarion on pathogenesis and disease severity in a chinchilla model of experimental otitis media. Chinchillas were challenged with NTHI variant populations that were either inoculated ON and remained ON, inoculated OFF and shifted ON, or inoculated OFF and remained OFF, within the middle ear. We show that populations that shift from OFF to ON within the middle ear induce significantly greater disease severity than populations that are unable to shift. These observations port the importance of phasevarion switching in NTHI pathogenesis and the necessity to considered phasevarion regulation when developing methods to treat and prevent infection.

Original languageEnglish
Pages (from-to)817-824
Number of pages8
JournalJournal of Infectious Diseases
Volume214
Issue number5
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • Animal models
  • Biofilms
  • Chinchilla
  • Epigenetics
  • Phase variation

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