Mapping Genetic Determinants of Host Susceptibility to Pseudomonas Aeruginosa Lung Infection in Mice

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2016 May 13

PMID 27169516

Citations 9

Authors

Maura De Simone

Lorenza Spagnuolo

Nicola Ivan Lore

Cristina Cigana

Ida De Fino

Karl W Broman

Fuad A Iraqi

Alessandra Bragonzi

Affiliations

Soon will be listed here.

Abstract

Background: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown.

Results: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P . aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes.

Conclusions: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studies.

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