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BMC Genomics. 2016 May 11;17:351. doi: 10.1186/s12864-016-2676-4.

Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice.

Author information

1
Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
2
Department of Biostatistics & Medical Informatics, University of Wisconsin, Madison, WI, USA.
3
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel.
4
Infection and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. bragonzi.alessandra@hsr.it.

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.

KEYWORDS:

Candidate genes; Host susceptibility; Linkage analysis; Murine model; P. aeruginosa; Pneumonia; QTL mapping

PMID:
27169516
PMCID:
PMC4866434
DOI:
10.1186/s12864-016-2676-4
[Indexed for MEDLINE]
Free PMC Article

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