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Susceptibility to Klebsiella pneumonaie infection in collaborative cross mice is a complex trait controlled by at least three loci acting at different time points.

Vered K, Durrant C, Mott R, Iraqi FA - BMC Genomics (2014)

Bottom Line: 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.Distinct QTL were mapped at specific time points during the challenge.By using the sequence variations of the eight inbred strain founders of the CC to refine QTL localization we identify several candidate genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. fuadi@post.tau.ac.il.

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.

Conclusion: Host susceptibility to Kp is a complex trait, controlled by multiple genetic factors that act sequentially during the course of infection.

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Survival curves of representative collaborative cross lines after intraperitoneal infection withKlebsiella pneumoniae.
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Fig1: Survival curves of representative collaborative cross lines after intraperitoneal infection withKlebsiella pneumoniae.

Mentions: The 328 CC mice also responded variably with mean survival time between 1 to 12 days. Differences in survival between the 73 CC lines were highly significant (P < 0.0001). Figure 1 shows the percentage survival of a representative selection of susceptible, intermediate and resistant lines, Figure 2 shows the mean survival time (days) and standard deviation (s.d) of the representative selection CC lines and Additional file2: Table S2 summarize the mean survival time (days) and standard deviation (s.d) of the entire studied CC lines. Although the variation between lines was highly significant, indicating that the response to infection was heritable, there was also considerable variability within some lines. Mice that survived past the seventh day of infection tended to survive to the end of the experiment, suggesting this was a critical point in the disease progression.Figure 1


Susceptibility to Klebsiella pneumonaie infection in collaborative cross mice is a complex trait controlled by at least three loci acting at different time points.

Vered K, Durrant C, Mott R, Iraqi FA - BMC Genomics (2014)

Survival curves of representative collaborative cross lines after intraperitoneal infection withKlebsiella pneumoniae.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4201739&req=5

Fig1: Survival curves of representative collaborative cross lines after intraperitoneal infection withKlebsiella pneumoniae.
Mentions: The 328 CC mice also responded variably with mean survival time between 1 to 12 days. Differences in survival between the 73 CC lines were highly significant (P < 0.0001). Figure 1 shows the percentage survival of a representative selection of susceptible, intermediate and resistant lines, Figure 2 shows the mean survival time (days) and standard deviation (s.d) of the representative selection CC lines and Additional file2: Table S2 summarize the mean survival time (days) and standard deviation (s.d) of the entire studied CC lines. Although the variation between lines was highly significant, indicating that the response to infection was heritable, there was also considerable variability within some lines. Mice that survived past the seventh day of infection tended to survive to the end of the experiment, suggesting this was a critical point in the disease progression.Figure 1

Bottom Line: 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.Distinct QTL were mapped at specific time points during the challenge.By using the sequence variations of the eight inbred strain founders of the CC to refine QTL localization we identify several candidate genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. fuadi@post.tau.ac.il.

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.

Conclusion: Host susceptibility to Kp is a complex trait, controlled by multiple genetic factors that act sequentially during the course of infection.

Show MeSH
Related in: MedlinePlus