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

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32 Citations (Scopus)


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
JournalThe Journal of Infectious Diseases
Issue number5
Publication statusPublished - 1 Sept 2016


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

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