A genomic analysis of Clostridium difficile infections in blunt trauma patients

Abstract

Background: Evidence demonstrates that susceptibility to Clostridium difficile infection is related to host risk factors as much as bacterial potency. Using blood leukocyte genome-wide expression patterns of severe blunt trauma patients obtained by the National Institute of General Medical Sciences-sponsored Glue Grant Inflammation and the Host Response to Injury, we examined leukocyte genomic profiles of patients with C. difficile infection to determine preinfection and postinfection gene expression changes.

Methods: The genomic responses of 21 severe trauma patients were analyzed (5 C. difficile, 16 controls matched for age and severity of injury). After elimination of probe sets whose expression was below baseline or were unchanged, remaining probe sets underwent hierarchical clustering and principal component analysis. Molecular pathways were generated through Ingenuity Pathways Analysis.

Results: Supervised analysis demonstrated 118 genes whose expression in patients with C. difficile infection varied before and after their infection. Supervised analysis comparing patients with C. difficile infection with matched non-C. difficile patients before infection suggested that the expression of 501 genes were different in the two groups with up to 87% class prediction (p < 0.05). Many of these genes are related to cell-mediated immune responses, signaling, and interaction.

Conclusion: Genomic analysis of severe blunt trauma patients reveals a distinct leukocyte expression profile of C. difficile both before and after infection. We conclude that an association may exist between a severe trauma patient's leukocyte genomic expression profile and subsequent susceptibility to C. difficile infection. Further prospective expression analysis of this C. difficile population may reveal potential therapeutic interventions and allow early identification of C. difficile-susceptible patients.

Level of evidence: Prognostic/diagnostic study, level III.

Figure 1. Dendrograms and Heat Maps of Supervised Analysis (C. diff. cluster outlined in black)

A. 5 Patients before (β) and after (α) infection with C. diff. 118 genes were differentially expressed. B. 5 Patients with CDAD (1) compared to 16 age and ISS matched patients (0) without infection. 47 genes differentiated the groups. C. Comparison of 5 C. diff. patients (1) to 16 age and ISS matched controls (0) prior to infection. 501 genes differentiated the two groups with up to 87% class prediction.

Figure 2. Examples of Molecular Pathways from Ingenuity Analysis of C. diff. Patients Prior to Infection

A. Molecular pathway including genes involved in cell morphology, cellular growth and proliferation as well as cellular development. B. Molecular pathway representing genes in cell-to-cell signaling and interaction, hematological system development and function as well as immune cell trafficking.