Black Holes and Antivirulence Genes: Selection for Gene Loss as Part of the Evolution of Bacterial Pathogens

Abstract

This chapter discusses the concept of gene loss in the evolution of bacterial pathogens from commensals as a mechanism of fine-tuning pathogen genomes for maximal fitness in new host environments. It describes the nature of antivirulence genes and the pressures that drive selection for gene inactivation, and examines how this process complements the mechanisms of pathogen evolution through gene acquisition. Pathoadaptive mutation via gene loss complements bacterial pathogen evolution by gene acquisition. The evolutionary model of antagonistic pleiotrophy predicts that genes required for fitness in one niche may actually inhibit fitness in another environment that presents new selective pressures. “Black holes” in pathogen genomes are formed by inactivation or loss of ancestral genes that are incompatible with, and even antagonistic to, the pathogenic lifestyle. These incompatible genes are defined as antivirulence genes. Shigella serves as a model for pathoadaptive mutation by gene loss and gene inactivation. Converse Koch’s postulates are proposed as criteria for identification of antivirulence genes. New techniques such as phenotypic arrays, comparative genomic hybridization, and transposon site hybridization will improve the ability to identify pathoadaptive mutations in an organism. Pathoadaptive mutations played a critical role in Bacillus anthracis evolution and provide further evidence of the important contribution of the evolutionary pathway in niche adaptation and the generation of maximally fit pathogen clones.