Exploring the Evolution of Virulence Factors through Bioinformatic Data Mining

Abstract

The molecular evolution of virulence factors is a central theme in our understanding of bacterial pathogenesis and host-microbe interactions. Using bioinformatics and genome data mining, recent studies have shed light on the evolution of important virulence factor families and the mechanisms by which they have adapted and diversified in function. This perspective highlights three complementary approaches useful for studying the molecular evolution of virulence factors: identification and analysis of virulence factor homologs, detection of adaptations or functional shifts, and computational prediction of novel virulence factor families. Each of these research directions is associated with distinct questions, approaches, and challenges for future work. Moving forward, bioinformatics will continue to play a critical role in exploring the evolution of virulence factors, including those that target humans. By reconstructing past processes and events, we will be able to better interpret newly sequenced microbial genomes and detect future pathoadaptations.

Keywords: bioinformatics; microbial genomics; molecular evolution; pathogens; virulence factors.

FIG 1

Bioinformatically identified toxins provide insights into the evolutionary origins of major toxin families. (a and b) General overviews of the phylogenies of botulinum neurotoxin (BoNT) and diphtheria toxin (DT), including recently discovered homologs. (c) General model depicting the hypothetical evolution of an ancestral toxin that diversifies over time in terms of host, cell type, and substrate specificity. Changes in the catalytic domain (blue) are associated with alterations in substrate specificity, while changes in the binding domain (purple or red) are associated with alterations in host specificity and cell/tissue type (e.g., from the gut to the central nervous system [CNS]). This model is one potential explanation for observed sequence patterns in these toxin families.