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

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

Cite this

Brockman, Kenneth L ; Jurcisek, Joseph A ; Atack, John M ; Srikhanta, Yogitha N. ; Jennings, Michael P ; Bakaletz, Lauren O. / ModA2 phasevarion switching in nontypeable haemophilus influenzae increases the severity of experimental otitis media. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 5. pp. 817-824.
@article{6aabc86c90004259a94283ae84118e66,
title = "ModA2 phasevarion switching in nontypeable haemophilus influenzae increases the severity of experimental otitis media",
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.",
keywords = "Animal models, Biofilms, Chinchilla, Epigenetics, Phase variation",
author = "Brockman, {Kenneth L} and Jurcisek, {Joseph A} and Atack, {John M} and Srikhanta, {Yogitha N.} and Jennings, {Michael P} and Bakaletz, {Lauren O}",
year = "2016",
month = "9",
day = "1",
doi = "10.1093/infdis/jiw243",
language = "English",
volume = "214",
pages = "817--824",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "5",

}

ModA2 phasevarion switching in nontypeable haemophilus influenzae increases the severity of experimental otitis media. / Brockman, Kenneth L; Jurcisek, Joseph A; Atack, John M; Srikhanta, Yogitha N.; Jennings, Michael P; Bakaletz, Lauren O.

In: Journal of Infectious Diseases, Vol. 214, No. 5, 01.09.2016, p. 817-824.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - ModA2 phasevarion switching in nontypeable haemophilus influenzae increases the severity of experimental otitis media

AU - Brockman, Kenneth L

AU - Jurcisek, Joseph A

AU - Atack, John M

AU - Srikhanta, Yogitha N.

AU - Jennings, Michael P

AU - Bakaletz, Lauren O

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

KW - Animal models

KW - Biofilms

KW - Chinchilla

KW - Epigenetics

KW - Phase variation

UR - http://www.scopus.com/inward/record.url?scp=84988912794&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiw243

DO - 10.1093/infdis/jiw243

M3 - Article

VL - 214

SP - 817

EP - 824

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 5

ER -