IglE is an outer membrane-associated lipoprotein essential for intracellular survival and murine virulence of type A Francisella tularensis

Gregory T Robertson; Robert Child; Christine Ingle; Jean Celli; Michael V Norgard

doi:10.1128/IAI.00595-13

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IglE is an outer membrane-associated lipoprotein essential for intracellular survival and murine virulence of type A Francisella tularensis

Journal article

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IglE is an outer membrane-associated lipoprotein essential for intracellular survival and murine virulence of type A Francisella tularensis

Gregory T Robertson, Robert Child, Christine Ingle, Jean Celli and Michael V Norgard

Infection and immunity, Vol.81(11), pp.4026-4040

11/2013

DOI: https://doi.org/10.1128/IAI.00595-13

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https://hdl.handle.net/2376/101540

PMCID: PMC3811846

PMID: 23959721

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Abstract

Molecular Weight

Virulence Factors - genetics

Lipoproteins - genetics

Virulence

Francisella tularensis - chemistry

Genetic Complementation Test

Tularemia - microbiology

Tularemia - pathology

Lipoproteins - metabolism

Female

Membrane Proteins - metabolism

Francisella tularensis - genetics

Macrophages - microbiology

Disease Models, Animal

Cell Line

Membrane Proteins - genetics

Mice, Inbred C57BL

Genomic Islands

Lipoproteins - chemistry

Virulence Factors - chemistry

Microbial Viability

Gene Knockout Techniques

Mice, Inbred C3H

Animals

Membrane Proteins - chemistry

Virulence Factors - metabolism

Francisella tularensis - pathogenicity

Mice

IglE is a small, hypothetical protein encoded by the duplicated Francisella pathogenicity island (FPI). Inactivation of both copies of iglE rendered Francisella tularensis subsp. tularensis Schu S4 avirulent and incapable of intracellular replication, owing to an inability to escape the phagosome. This defect was fully reversed following single-copy expression of iglE in trans from attTn7 under the control of the Francisella rpsL promoter, thereby establishing that the loss of iglE, and not polar effects on downstream vgrG gene expression, was responsible for the defect. IglE is exported to the Francisella outer membrane as an ∼13.9-kDa lipoprotein, determined on the basis of a combination of selective Triton X-114 solubilization, radiolabeling with [(3)H]palmitic acid, and sucrose density gradient membrane partitioning studies. Lastly, a genetic screen using the iglE-null live vaccine strain resulted in the identification of key regions in the carboxyl terminus of IglE that are required for intracellular replication of Francisella tularensis in J774A.1 macrophages. Thus, IglE is essential for Francisella tularensis virulence. Our data support a model that likely includes protein-protein interactions at or near the bacterial cell surface that are unknown at present.

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Title: IglE is an outer membrane-associated lipoprotein essential for intracellular survival and murine virulence of type A Francisella tularensis
Creators: Gregory T Robertson - Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Robert Child
Christine Ingle
Jean Celli
Michael V Norgard
Publication Details: Infection and immunity, Vol.81(11), pp.4026-4040
Academic Unit: Paul G. Allen School for Global Animal Health
Publisher: United States
Grant note: U54 AI057156 / NIAID NIH HHS
Identifiers: 99900546550401842
Language: English
Resource Type: Journal article