Survey of Genomes - Yersinia pestis strain KIM

In this episode from the survey of genomes, Alexis Polcawich from the 2019 Hiram College Genetics course talks about Yersinia pestis, the microbe behind one of the deadliest diseases in human history - the Black Plague.

Welcome to Genomics Revolution. My name is Alexis Polcawich from the 2019 Hiram College Genetics course hosting this episode on the genome called Yersinia Pestis. This is a gram negative, nonmotile, rod-shaped coccobacillus bacteria that does not form spores and is a facultative anaerobe. This bacterium was discovered in 1894 by Alexandre Yersin in Hong Kong. Yersin was able to isolate the bacterium in culture and identified it via microscope. Jean-Paul Simond was Yersin’s inspiration to do so as in 1898 he discovered that bacteria was transferred from rodents by flea bites, and Yersin thought it would be beneficial to learn more about such bacteria. You can probably guess where this is going… By doing so, he discovered that Yersinia pestis was responsible for causing the plague in humans. This podcast is going to discuss the Yersinia pestis KIMstrain which is responsible for the both the bubonic and pneumonic plagues. The KIM strain is believed to be the first strain discovered as the Yersinia pestis bacteria was found while researchers were looking into the underlying causes of the bubonic plague.

Yersinia pestis is claimed to be a potential weapon of bioterrorism because it can effectively evade it’s host’s immune system and otherwise go unnoticed until it is too late and the symptoms become too severe for the body to fight them off. This tiny bacterium is responsible for drastically high mortalities throughout the course of history, some people today still become infected by it. However, it is now treatable with present day antibiotics and does not always result in death unless the case is very severe. 

The genome of Yersinia pestis contains one circular chromosome of 4,600,755 bp with an average G+C content of 47.64%. This genome encompasses 4,198 open reading framesand contains three different plasmids called pPCP1, pMT1, and pCD1. 

One key finding was in a study done in 2011 that looked at developing a possible vaccine for the plaque by constructing a mutant strain of Yersinia pestis that expressed lpxL from the chromosome which resulted in almost all of the lipid A in the cell being hexa-acylated. This means that The lpxL gene is not a gene that normal wild type Yersinia pestis carry. The absence of this protein leads to the production of tetra-acylated lipid A which does not bind to the host receptor, therefore failing to simulate the inflammatory response normally induced by lipid A. By making these hexa-acylated, this allows the inflammation process to happen and the body can start to effectively fight off the bacteria. 

A second key finding is now that the genome of this bacterium is sequenced, researches can now trace potentialoutbreaks and analyze the evolution of the bacteria. The differences in certain regions such as the number of inverted/rearranged segments in the different strains of Yersinia pestis in different regions of the world shows how quickly certain strains are mutating compared to others. This can help researches and epidemiologists predict what to expect from a certain strain over a particular period of time and keep up with effective medications/treatments. 
A third key finding is that researches can use the sequenced genome and compare it to other sequenced bacterium genomes to identify close relatives of Yersinia pestis. This is very important because if there happens to be a certain bacteria that is very similar to Yersinia pestis and there is already an effective medication found to treat that bacteria, then maybe that medication can be used to treat Yersinia pestis as well. In the study done in 2002 on the genome sequence of Yersinia pestisKIM, the genome was continuously compared to E. Coli K-12. The origin, terminus, and most recent genes encoding DNA replication proteins are very similar to those of E. Coli. Being able to relate Yersinia pestis to a bacteria that is already well known provides researchers with the means to answer a lot of previously unanswerable questions and can even inspire further experiments to test new hypotheses evolving from current knowledge of similar bacterial strains. 

Who knew such a tiny organism could be so deadly that it is responsible for billions of deaths throughout history. Without geneticists and epidemiologists (even though they weren’t called such back in the 18-1900’s) the human population could have been completely wiped out by now. 
References
(1) Auerbach et al., 2007. Plos one 2(8): e770. Yersinia pestis Evolution on a Small Timescale: Comparison of Whole Genome Sequences from North America. https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000770&type=printable
(2) Butler et al., 2014. Clinical Microbiology and Infection 20: 202-09. Plague history: Yersin’s discovery of the causative bacterium in 1894 enabled, in the subsequent century, scientific progress in understanding the disease and the development of treatments and vaccines. https://www.sciencedirect.com/science/article/pii/S1198743X14608582?via%3Dihub
(3) Losada et al., 2011. Plos One 6(4): e19054. Genome Sequencing and Analysis of Yersinia pestis KIM D27, and Avirulent Strain Exempt from Select Agent Regulation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084740/pdf/pone.0019054.pdf
(4) Deng et al., 2002. American Society for Microbiology184: 4601-11. Genome Sequence of Yersinia pestis KIM.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC135232/
(5) Sun et al., 2011. Vaccine 29(16): 2986-98. A live attenuated strain of Yersinia pestis KIM as a vaccine against the plague. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073832/
(6) Ziets et al., 2004. International Journal of Hygiene and Environmental Health 207: 165-178. The history of the plague and the research on the causative agent Yersinia pestis.https://www.sciencedirect.com/science/article/pii/S1438463904702771