ModA2 Phasevarion Switching in Nontypeable Haemophilus influenzae Increases the Severity of Experimental Otitis Media. J Infect Dis 2016 Sep 01;214(5):817-24
Date
06/12/2016Pubmed ID
27288538Pubmed Central ID
PMC4978376DOI
10.1093/infdis/jiw243Scopus ID
2-s2.0-84988912794 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
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 support the importance of phasevarion switching in NTHI pathogenesis and the necessity to considered phasevarion regulation when developing methods to treat and prevent infection.
Author List
Brockman KL, Jurcisek JA, Atack JM, Srikhanta YN, Jennings MP, Bakaletz LOAuthor
Kenneth Brockman PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigenic Variation
Antigens, Bacterial
Chinchilla
Cohort Studies
Disease Models, Animal
Haemophilus Infections
Haemophilus influenzae
Otitis Media
Severity of Illness Index