Integrative conjugative element ICE-βox confers oxidative stress resistance to Legionella pneumophila in vitro and in macrophages

ABSTRACT Integrative conjugative elements (ICEs) are mobile blocks of DNA that can contribute to bacterial evolution by self-directed transmission of advantageous traits. Here, we analyze the activity of a putative 65-kb ICE harbored by Legionella pneumophila using molecular genetics, conjugation as...

Full description

Saved in:
Bibliographic Details
Published in:mBio 2014-04, Vol.5 (3), p.e01091
Main Authors: Flynn, Kaitlin J, Swanson, Michele S
Format: Article
Language:English
Subjects:
Animals
beta-Lactam Resistance - genetics
DNA Transposable Elements
Female
Gene Order
Genes, Bacterial
Genetic Fitness
Genetic Loci
Legionella pneumophila - physiology
Macrophages - metabolism
Macrophages - microbiology
Mice
Mutagenesis, Insertional
NADPH Oxidases - metabolism
Oxidants - pharmacology
Oxidative Stress - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:ABSTRACT Integrative conjugative elements (ICEs) are mobile blocks of DNA that can contribute to bacterial evolution by self-directed transmission of advantageous traits. Here, we analyze the activity of a putative 65-kb ICE harbored by Legionella pneumophila using molecular genetics, conjugation assays, a phenotype microarray screen, and macrophage infections. The element transferred to a naive L. pneumophila strain, integrated site-specifically, and conferred increased resistance to oxacillin, penicillin, hydrogen peroxide, and bleach. Furthermore, the element increased survival of L. pneumophila within restrictive mouse macrophages. In particular, this ICE protects L. pneumophila from phagocyte oxidase activity, since mutation of the macrophage NADPH oxidase eliminated the fitness difference between strains that carried and those that lacked the mobile element. Renamed ICE-βox (for β-lactam antibiotics and oxidative stress), this transposable element is predicted to contribute to the emergence of L. pneumophila strains that are more fit in natural and engineered water systems and in macrophages. IMPORTANCE Bacteria evolve rapidly by acquiring new traits via horizontal gene transfer. Integrative conjugative elements (ICEs) are mobile blocks of DNA that encode the machinery necessary to spread among bacterial populations. ICEs transfer antibiotic resistance and other bacterial survival factors as cargo genes carried within the element. Here, we show that Legionella pneumophila, the causative agent of Legionnaires' disease, carries ICE-βox, which enhances the resistance of this opportunistic pathogen to bleach and β-lactam antibiotics. Moreover, L. pneumophila strains encoding ICE-βox are more resistant to macrophages that carry phagocyte oxidase. Accordingly, ICE-βox is predicted to increase the fitness of L. pneumophila in natural and engineered waters and in humans. To our knowledge, this is the first description of an ICE that confers oxidative stress resistance to a nosocomial pathogen.
ISSN:2161-2129
2150-7511
DOI:10.1128/mBio.01091-14