Host-microbe interaction systems biology: lifecycle transcriptomics and comparative genomics

Abstract

The use of microarray and comparative genomic technologies for the analysis of host-pathogen interactions has led to a greater understanding of the biological systems involved in infectious disease processes. Transcriptome analysis of intracellular pathogens at single or multiple time points during infection offers insight into the pathogen intracellular lifecycle. Host-pathogen transcriptome analysis in vivo, over time, enables characterization of both the pathogen and the host during the dynamic, multicellular host response. Comparative genomics using hybridization microarray-based comparative whole-genome resequencing or de novo whole-genome sequencing can identify the genetic factors responsible for pathogen evolutionary divergence, emergence, reemergence or the genetic basis for different pathogenic phenotypes. Together, microarray and comparative genomic technologies will continue to advance our understanding of pathogen evolution and assist in combating human infectious disease.

Figure 1. Principal components analysis plot representing the whole-genome, differential expression profile of Coxiella burnetii under different growth conditions

Each sphere in the figure is an individual biological replicate and represents all the data from one microarray chip. The orange spheres labeled ‘infected vero’ represent mRNA isolated from C. burnetii infected Vero cells following 5 days of intracellular infection. The red spheres labeled ‘CCM’ represent mRNA isolated from C. burnetii incubated in CCM for 24 h. The blue spheres labeled ‘carry over’ represent mRNA extracted from the original inoculum of C. burnetii cells that were made by purifying the pathogen from 7-day-infected Vero cells. Therefore, ‘carry over’ represents the mRNA content carried over initially into the new 5-day Vero cell-infected environment and the 24 h CCM environment. Principal components analysis plots allow rapid data visualization of groupings of biological replicates within their particular treatment, relative to the separation or distance between the different treatment groups. The tighter the groupings and the greater the distance between groups, the greater the list of genes demonstrating significant differential expression changes between treatments. CCM: Complex Coxiella medium; PC: Principal component.