title: Susceptibility to Klebsiella pneumonaie infection in collaborative cross mice is a complex trait controlled by at least three loci acting at different time points.
abstract: BACKGROUND
  Klebsiella pneumoniae (Kp) is a bacterium causing severe pneumonia in immunocompromised hosts and is often associated with sepsis. With the rise of antibiotic resistant bacteria, there is a need for new effective and affordable control methods; understanding the genetic architecture of susceptibility to Kp will help in their development. We performed the first quantitative trait locus (QTL) mapping study of host susceptibility to Kp infection in immunocompetent Collaborative Cross mice (CC). We challenged 328 mice from 73 CC lines intraperitoneally with 104 colony forming units of Kp strain K2. Survival and body weight were monitored for 15 days post challenge. 48 of the CC lines were genotyped with 170,000 SNPs, with which we mapped QTLs.
  
  
  RESULTS
  CC lines differed significantly (P < 0.05) in mean survival time, between 1 to 15 days post infection, and broad sense heritability was 0.45. Distinct QTL were mapped at specific time points during the challenge. A QTL on chromosome 4 was found only on day 2 post infection, and QTL on chromosomes 8 and 18, only on day 8. By using the sequence variations of the eight inbred strain founders of the CC to refine QTL localization we identify several candidate genes.
  
  
  CONCLUSIONS
  Host susceptibility to Kp is a complex trait, controlled by multiple genetic factors that act sequentially during the course of infection.
authors.forename: Karin
authors.initials: K
authors.lastname: Vered
authors.forename: Caroline
authors.initials: C
authors.lastname: Durrant
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. fuadi@post.tau.ac.il.
authors.forename: Fuad A
authors.initials: FA
authors.lastname: Iraqi
mesh_terms: D000818:Animals; D033481:Chromosomes, Mammalian; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D007710:Klebsiella Infections / Q000235:genetics* / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci