ModA2 Phasevarion Switching in Nontypeable Haemophilus influenzae Increases the Severity of Experimental Otitis Media.
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.
Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital The Ohio State University College of Medicine, Columbus, Ohio.
Kenneth L
KL
Brockman
Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital The Ohio State University College of Medicine, Columbus, Ohio.
Joseph A
JA
Jurcisek
Institute for Glycomics, Griffith University, Gold Coast, Australia.
John M
JM
Atack
Institute for Glycomics, Griffith University, Gold Coast, Australia.
Yogitha N
YN
Srikhanta
Institute for Glycomics, Griffith University, Gold Coast, Australia.
Michael P
MP
Jennings
Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital The Ohio State University College of Medicine, Columbus, Ohio.
Lauren O
LO
Bakaletz
D000818:Animals; D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D002682:Chinchilla; D015331:Cohort Studies; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000382:microbiology* / Q000473:pathology*; D006193:Haemophilus influenzae / Q000472:pathogenicity*; D010033:Otitis Media / Q000382:microbiology* / Q000473:pathology*; D012720:Severity of Illness Index
D000942:Antigens, Bacterial
animal models; biofilms; chinchilla; epigenetics; phase variation