Survey of Genomes - Rickettsia prowazekii
What do lice, flying squirrels, and World War I have in common? That weird question is answered by Jake Lininger from the 2019 Hiram College Genetics course as he introduces us to the cause of epidemic typhus - the pathogenic bacterium Rickettsia prowazekii.
During WWI, epidemic typhus infected around 30 million humans (1). R. prowazekii had been discovered previously as a causal agent for typhus, or typhus fever, but how it infects humans was yet to be discovered. In 1928, Dr. Charles Nicolle received a Nobel prize for discovering the vector for this infection; human body louse. Humans that develop typhus are infested with lice that carry R. prowazekii until skin is broken and the bacteria is able to invade the body. R. prowazekii is transmitted via the feces of lice. The bacteria remain infective for months, or in the case of Brill Zinsser Disease, R. prowazekii remains viable for years and may infect when the host’s defenses are down. Without treatment, fatalities were around 30%. Today, antibiotics are used to treat the infection. While infection is rarer today than in the 1900s, lice of the flying squirrel look to be the leading carrier of R. prowazekii in North America.
In 1998, R. prowazekii was the first alpha-proteobacterial, gram-negative genome to be sequenced. The strain used was the Madrid E strain of R. prowazekii, named after a patient who died in 1941 of epidemic typhus. The single circular chromosome of R. Prowazekii has 1,111,523 base pairs. The genome consists of 834 protein-coding genes, averaging in length of 1,005 base pairs. This represents about 75% of the genome leaving the rest to non-coding DNA (1). The large amount of non-coding DNA along with other factors of the genome point to evolutionary ties to mitochondria via horizontal gene transfer.
Since the sequencing of R. prowazekii in 1998, other Rickettsia species have been sequenced (2). Rickettsia conorii, known for causing Mediterranean spotted fever, exhibits 804 of the 834 genes from R. prowazekii. Data suggests a divergence of the genus while they exhibited a near perfect collinearity. Another study discussed R. prowazekii, R. conorii, and R. typhi in having similar sequences revealing the presence of four genes with potential membranolytic activities (3). The same paper also hypothesized and proved that expression in Salmonella of the R. prowazekii gene could lead to host cell infection.
Rickettsia prowazekii is classified as a bioterrorism agent due to its small size, low infectious dose, and high morbidity and mortality. Antibiotic resistant strains of R. prowazekii could be engineered to inflict a lot of damage (3). Regular bathing and laundering can prevent the spread of human lice, reducing the probability of R. prowazekii infection. And, for as cute as having a pet flying squirrel sounds, it is probably best to avoid contact with those little guys. Thanks for tuning in.
1) Andersson, S. G., Zomorodipour, A., Andersson, J. O., Sicheritz-Pontén, T., Alsmark, U. C. M., Podowski, R. M., ... & Kurland, C. G. (1998). The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature, 396(6707), 133.
2) Ogata, H., Audic, S., Renesto-Audiffren, P., Fournier, P. E., Barbe, V., Samson, D., ... & Raoult, D. (2001). Mechanisms of evolution in Rickettsia conorii and R. prowazekii. Science, 293(5537), 2093-2098.
3) Whitworth, T., Popov, V. L., Yu, X. J., Walker, D. H., & Bouyer, D. H. (2005). Expression of the Rickettsia prowazekii pld or tlyC gene in Salmonella enterica serovar Typhimurium mediates phagosomal escape. Infection and immunity, 73(10), 6668-6673.