Retracing the Evolutionary Path that Led to Flea-Borne Transmission of Yersinia pestis

Abstract

Summary Yersinia pestis is an arthropod-borne bacterial pathogen that evolved recently from Yersinia pseudotuberculosis, an enteric pathogen transmitted via the fecal-oral route. This radical ecological transition can be attributed to a few discrete genetic changes from a still-extant recent ancestor, thus providing a tractable case study in pathogen evolution and emergence. Here, we determined the precise genetic and mechanistic basis of the evolutionary adaptation of Y. pestis to flea-borne transmission. Remarkably, only four minor changes in the bacterial progenitor, representing one gene gain and three gene losses, enabled transmission by flea vectors. All three loss-of-function mutations enhanced c-di-GMP-mediated bacterial biofilm formation in the flea foregut that greatly increased transmissibility. Our results suggest a step-wise evolutionary model in which Y. pestis emerged as a flea-borne clone, with each genetic change incrementally reinforcing the transmission cycle. The model conforms well to the ecological theory of adaptive radiation.

Ecological Opportunity, Evolution, and the Emergence of Flea-Borne Plague

“…In these fleas, the infection is restricted primarily to the flea hindgut. The midgut is only transiently infected, the proventriculus never is, and there is no evidence of biofilm formation in the flea digestive tract (41,42). Consistent with this picture and with earlier reports, no transmission of Y. pseudotuberculosis by infected fleas has ever been detected (42,43).…”

“…The midgut is only transiently infected, the proventriculus never is, and there is no evidence of biofilm formation in the flea digestive tract (41,42). Consistent with this picture and with earlier reports, no transmission of Y. pseudotuberculosis by infected fleas has ever been detected (42,43). In contrast, blood meals containing Y. pestis are completely nontoxic to fleas-no initial morbidity or mortality is seen, just as in fleas that feed on sterile blood.…”

“…Thus, the original function of all three pseudogenes (rcsA and the two PDE genes that function to degrade c-di-GMP) involve pathways predicted to suppress biofilm development, suggestive that their loss would have been beneficial to the biofilm-dependent mechanism by which fleas transmit Y. pestis. Support for this hypothesis came from experiments showing that allelic exchange replacement of each of the three pseudogenes with the functional ortholog from Y. pseudotuberculosis resulted in attenuation of the Y. pestis in vitro biofilm phenotype (42). However, biofilm formation is highly dependent on environmental conditions, and biofilm regulation is different in the flea digestive tract than in vitro (57).…”

“…Y. pestis never colonizes the flea hindgut but, instead, grows in the form of large multicellular biofilmlike aggregates in the midgut and proventriculus. Efficient transmission via fleabite occurs throughout the month following the infectious blood meal (42).…”

Transmission in the Origins of Bacterial Diversity, From Ecotypes to Phyla

“…For example, Yersinia pseudotuberculosis is a gut pathogen transmitted by the fecal-oral route, but it has the capacity to be lethal when it (rarely) invades the lungs or blood (176). The plague bacterium, Yersinia pestis, which is derived from Y. pseudotuberculosis, inherited its ancestor's capacity for systemic infection, but it evolved to reside primarily in the hosts' blood through transmission by fleas (177). Similarly, ecotypes within Streptococcus pyogenes are differentiated to infect the throat, causing strep throat, versus the skin, causing impetigo (178).…”