Ecology and Evolution of Chromosomal Gene Transfer between Environmental Microorganisms and Pathogens

Evolutionary trajectories of bacterial pathogens. (A) The process of speciation of a pathogen (larger circles) such as Y. pestis. This process usually begins with the acquisition, by HGT, of a set of genes (red circle) that allow the shift of the pathogen’s habitat from the environment to an infected host ( 1 ). If the rate of transmission is high enough, the newborn pathogen will disseminate among different individuals ( 2 ) and evolve by different mechanisms that include mutation and eventually genome reduction ( 4 ). These evolutionary processes might cause the deadaptation of the pathogen to its original habitat, in which case the chances of the microorganism recolonizing natural ecosystems will be low ( 3 ). Once the organism is a pathogen, it can change host specificity by acquiring novel genes ( 5 ) and eventually by losing of determinants unneeded in the novel host ( 6 ). In all cases, the integration of the acquired elements into the preformed bacterial metabolic and regulatory networks will be tuned by mutation. (B) The process of short-sighted evolution of opportunistic pathogens with an environmental origin, like P. aeruginosa. These microorganisms infect patients, presenting a basal disease, using virulence determinants already encoded in their genomes ( 7 ). During chronic infection, the infective strain evolves mainly by mutation and genome rearrangements ( 8 ). However, since it only infects people with a basal disease, transmission rates are usually low, which precludes clonal expansion and further diversification. Since adaptation to the new host is of no value for colonizing the environmental habitat ( 9 ), this is a dead-end evolutionary process. (C) The evolution of pathogens such as V. cholerae that present virulence determinants with a dual role in the environment and for infections, in which case the colonization of one of these two habitats does not severely compromise the colonization of the other ( 10 ). Reproduced with permission from reference 8 .

Evolution of Y. pestis. The process of Y. pestis speciation from an environmental, nonpathogenic ancestor is a good example of the evolutionary steps that are involved in the emergence of bacterial pathogens. This process began with the acquisition of the plasmid pCD1 by environmental Yersinia. This plasmid harbors genes encoding virulence determinants such as type III secretion systems and effector Yop proteins. From this ancestor of virulent Yersinia species, two branches have evolved. One diverged through the acquisition of the Yersinia stable toxin (Yst) and led to the speciation of Y. enterocolitica. This species has further evolved through acquisition and loss of genes (not shown in this figure). The other branch diverged through the acquisition of the high pathogenicity island (HPI*), which encodes an iron-uptake system and is present as well in different Enterobacteriaceae, and by the incorporation of insecticidal genes. Y. pestis is a successful clone that emerged recently from Y. pseudotuberculosis through the acquisition of the plasmids pCP1, which encodes the plasminogen activator gene, and pMT1, which allows colonization of the gut of fleas. The loss of insect toxins is an important event for the persistence of Y. pestis in its insect vectors. The acquisition of insertion sequences is the basis of the genome rearrangements and gene loss of Y. pestis. Finally, the entire process of adaptation to a new host is modulated by the mutation-driven optimization of the regulatory and metabolic networks of the pathogen. This evolutionary process is described in more detail in references 33 , 37 , and 105 . Reproduced with permission from reference 8 .

Exaptation and gene decontextualization in the evolution of antibiotic resistance. Antibiotic resistance genes (r) have evolved for millions of years located in the chromosomes of their original hosts (a). During this evolution, the expression of these determinants (R) from their promoters (P) has been finely tuned to respond to several signals that might include the response to environmental and metabolic changes (blue arrows). Besides, the determinants encoded by these genes are integrated in physiological networks, where they can play a role as metabolic enzymes. S1 to S3 represent metabolites of the same pathway, and A1 and B1 metabolites of other interconnected pathways. When these genes are integrated in gene capture (for instance, an integron) and transfer units (for instance, a plasmid), they can be transferred to a new host and submitted to strong antibiotic selective pressure (b), and they can be constitutively expressed from a strong promoter (P) present in the capture unit and therefore lack the regulatory and physiological network encountered in the original host (gene decontextualization). Under these circumstances, the only function these determinants can play is antibiotic resistance, in such a way that this functional shift is not the consequence of adaptive changes in the determinants but rather of changes in their environment (exaptation). Reproduced with permission from reference 127 .