Faculty Collaboration Database

The ModA2 Phasevarion of nontypeable Haemophilus influenzae Regulates Resistance to Oxidative Stress and Killing by Human Neutrophils. Sci Rep 2017 Jun 09;7(1):3161

Date

06/11/2017

Pubmed ID

28600561

Pubmed Central ID

PMC5466613

DOI

10.1038/s41598-017-03552-9

Scopus ID

2-s2.0-85020676207 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

Nontypeable Haemophilus influenzae (NTHI) is the causative agent of multiple respiratory tract infections. Several human pathogens, including NTHI, possess a novel genetic system, termed the phasevarion, which mediates a rapid and reversible change in the expression of many genes throughout the chromosome. This occurs by phase variation of a single gene (modA) that encodes a DNA methyltransferase and results in two phenotypically distinct subpopulations, ON and OFF. NTHI encounters many pressures within the various microenvironments of its human host as the disease course evolves from one of asymptomatic nasopharyngeal carriage to overt disease. These include oxidative stresses, which are present throughout the respiratory tract. To persist in the human nasopharynx and as a pathogen throughout the airways, NTHI must be able to mitigate toxic levels of oxidative stress. Here we show that expression of ModA2, modA2 ON status, resulted in increased sensitivity to oxidative stress. Furthermore, the modA2 ON status resulted in decreased resistance to neutrophil-mediated killing, which resulted in selection for the modA2 OFF subpopulation in an ex vivo survival assay. These findings highlight the importance of the ModA2 phasevarion in adaptation to innate host defences and reveal an additional microenvironmental pressure that selected for a specific ModA2 subpopulation.

Author List

Brockman KL, Branstool MT, Atack JM, Robledo-Avila F, Partida-Sanchez S, Jennings MP, Bakaletz LO

Author

Kenneth Brockman PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Child
Chromosomes, Bacterial
DNA (Cytosine-5-)-Methyltransferases
Gene Expression Regulation, Bacterial
Haemophilus Infections
Haemophilus influenzae
Host-Pathogen Interactions
Humans
Microbial Viability
Nasopharynx
Neutrophils
Oxidative Stress
Phagocytosis
Primary Cell Culture
Reactive Oxygen Species