A few thousand years ago, a bacterium that inhabited the guts of rodents and a variety of other mammals transformed its lifestyle. Instead of relying on faecal contamination of food and water to pass from an infected animal to an uninfected one, it found ways to use fleas, which fed on those animals, as an agent for its transmission. The stage was set for a microbe that humanity has feared down the ages — Yersinia pestis , the pathogen that causes plague.
Humans can get plague when bitten by bacteria-laden fleas or by handling infected animals.
In a paper titled ‘Retracing the evolutionary path that led to flea-borne transmission of Yersinia pestis, ’ a team of scientists led by plague researcher B. Joseph Hinnebusch at the U.S. National Institute of Allergy and Infectious Diseases showed how such a transformation could have occurred.
Genetic analyses of Y. pestis strains collected from around the world indicated that the pathogen emerged in central China less than 6,400 years ago. “Remarkably, only four minor changes in the bacterial progenitor, representing one gene gain and three gene losses,” enabled transmission by fleas, they noted in the paper, which was published last week in Cell Host & Microbe .
Y. pestis evolved as a variant of the bacterium Y. pseudotuberculosis . Although the latter lived in the guts of rodents and other mammals, it might enter the bloodstream of those animals in certain circumstances. The bacteria could then be imbibed by fleas that fed on those animals.
When researchers fed Xenopsylla cheopis rat fleas with blood containing Y. pseudotuberculosis , the bacterium grew only in the rear portion of the fleas’ alimentary tract, the hindgut. Y. pestis , on the other hand, colonised the fleas’ midgut as well as proventriculus, a chamber linking the midgut to the oesophagus.
An important step came. Y. pseudotuberculosis picked up the ymt gene from a completely different bacterium.
The scientists showed that when the ymt gene was introduced into Y. pseudotuberculosis , its infectivity then extended to the fleas’ mid-gut. Acquisition of this gene allowed the bacterium to exploit “the abundant resources and scant competition in the flea midgut to reproduce to large numbers,” they pointed out in the paper.
When a flea feeds on an animal infected with Y. pestis , the bacteria it ingests replicate in the mid-gut. Within days, the bacteria begin to form clumps, known as biofilms.
These clumps eventually block the proventriculus. Once that chamber is blocked, the blood sucked in by the hungry flea can no longer enter its midgut. Instead, the blood ends up being regurgitated, taking with it large quantities of bacteria. In this manner, the microbe gets injected into an uninfected animal when the fleas bite it.
In Y. pestis , three genes involving in limiting biofilm development have degenerated and become dysfunctional. When functional versions of these genes were replaced with the ones found in Y. pestis , Y. pseudotuberculosis was able to grow in the proventriculus and block it. Likewise, introducing the ancestral versions of the three genes completely eliminated the ability of Y. pestis to produce proventricular-blocking biofilm in fleas.
The scientists also demonstrated Y. pseudotuberculosis with the four genetic changes — the ymt gene and the Y. pestis form of the three biofilm-related genes — was transmitted by fleas just as well as Y. pestis .
The evolutionary history of Y. pestis provided an example of “how gene loss can be as critical to the evolutionary process as gene acquisition,” they commented.
