Yersinia pestis, the causative agent of the “Black Death” or “Bubonic” plague, has been a scourge of human civilization. One of the most virulent bacterial pathogens known, killing nearly 90% of those infected, Y. pestis was responsible for three historic pandemics that shattered whole societies. And plague is still with us. In Madagascar, a naturally antibiotic-resistant strain of plague erupted in the 1990s. In western North America, Y. pestis lurks in wild rodent populations. Throughout the world, there is new fear of Y. pestis as a bioterror agent.
Now a new and revealing portrait of this old nemesis is emerging from Lawrence Livermore National Laboratory. Scientists using advanced robotic high-throughput technologies have completed what is believed to be one of the most comprehensive and rapid studies ever of how growth conditions affect the virulence of a deadly bacterium. Ann E. Holtz who works in the laboratory of Sandra McCutchen-Maloney used a battery of phenotype array machines, pre-loaded 96-well plates, and robotic observers to chart the effects of 2,000 nutrients and chemicals, including about 240 different antibiotics, on the viability of Y. pestis under four separate, physiologically relevant growth conditions. Traditional studies of pathogens examined one to two dozen parameters under one or two growth conditions. In contrast the new technologies allowed Livermore researchers, in effect, to conduct 8,000 experiments in about a week.
The picture drawn by Holtz from her high-throughput data shows Y. pestis to be even tougher than suspected under conditions that mimic its life outside the human host, and possibly less vulnerable under human infection conditions to antibiotics currently used to treat plague, such as kanamycin, doxycycline and tetracycline. The researchers caution that these results are preliminary and will require further tests.