Black holes, antivirulence genes, and gene inactivation in the evolution of bacterial pathogens

Abstract

The evolution of bacterial pathogens from nonpathogenic ancestors is marked principally by the acquisition of virulence gene clusters on plasmids and pathogenicity islands via horizontal gene transfer. The flip side of this evolutionary force is the equally important adaptation of the newly minted pathogen to its new host niche. Pathoadaptive mutations take the form of modification of gene expression such that the pathogen is better fit to survive within the new niche. This mini-review describes the concept of pathoadaptation by loss of gene function. In this process, genes that are no longer compatible with the novel lifestyle of the pathogen are selectively inactivated either by point mutation, insertion, or deletion. These genes are called 'antivirulence genes'. Selective pressure sometimes leads to the deletion of large regions of the genome that contain antivirulence genes generating 'black holes' in the pathogen genome. Inactivation of antivirulence genes leads to a pathogen that is highly adapted to its host niche. Identification of antivirulence genes for a particular pathogen can lead to a better understanding of how it became a pathogen and the types of genetic traits that need to be silenced in order for the pathogen to colonize its new host niche successfully.

Loss of a Biofilm-Inhibiting Glycosyl Hydrolase during the Emergence of Yersinia pestis

“…By increasing the stability of the Y. pestis biofilm ECM in the flea, the loss of glycosyl hydrolase activity may have been an incremental step in the evolution of vector-borne transmission. Thus, like the recently described gene rcsA (46a), nghA may represent an antitransmission factor, analogous to antivirulence genes that enhance bacterial fitness in mammalian hosts (38), and its inactivation in Y. pestis may be an example of selective gene loss that contributed to the emergence of fleaborne transmission.…”

The influence of the accessory genome on bacterial pathogen evolution

“…12 It is well established that plasmids in a variety of prokaryotes carry and distribute a plethora of genes conferring adaptation, such as resistance to antibacterial compounds against human, animal and plant pathogens, virulence genes, ultraviolet resistance genes, detoxifying enzymes, bacteriocins and enzymes for secondary metabolism. 2,[13][14][15][16][17][18] A remarkable aspect of plasmids as MGEs is that they can hold and transfer large amounts of DNA, allowing for quantum leap 19,20 evolution and the acquisition of very complex phenotypes, including the transformation of nonpathogenic or low virulence bacteria into devastating pathogens of plants and animals. For example, the enterobacterium Pantoea agglomerans (syn.…”

Genetics and Virulence Association of the Shigella flexneri Sit Iron Transport System

“…Some of the insertions, termed pathogenicity islands (PAI), are quite large and include genes that increase virulence or fitness. Deletions in the chromosome may also affect pathogenicity; for example, the deletion of lysine decarboxylase genes in S. flexneri is associated with increased virulence (25,26).…”