Flying Squirrel–associated Typhus, United States

Reynolds, Mary G.; Krebs, John W.; Comer, James A.; Sumner, John W.; Rushton, Thomas; López, Carlos E.; Nicholson, William L.; Rooney, Jane; Lance-Parker, Susan; McQuiston, Jennifer H.; Paddock, Christopher D.; Childs, James E.

doi:10.3201/eid0910.030278

Cited by 54 publications

(28 citation statements)

References 12 publications

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“…Infection with R. prowazekii continues to be sporadically reported in the United States in association with exposure to flying squirrels [5,6]. Although no fatal cases have been reported to date in association with sylvatic typhus, severe cases requiring hospitalization and intensive care have occurred, and it is presumed that these infections carry the potential for fatal outcome if not recognized and promptly treated.…”

Section: Table 3 Clinical Signs and Symptoms Associated With Selectementioning

confidence: 97%

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Brill‐Zinsser Disease in a Patient Following Infection with Sylvatic Epidemic Typhus Associated with Flying Squirrels

et al. 2010

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Section: Table 3 Clinical Signs and Symptoms Associated With Selectementioning

confidence: 97%

“…There have been at least 47 cases documented in humans since 1976 (Centers for Disease Control and Prevention, unpublished data) [5,6]. Most of these cases had reported contact prior to illness onset with the southern flying squirrel, Glaucomys volans, which serves as a zoonotic reservoir for a sylvatic cycle of infection [5,6].…”

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confidence: 97%

Brill‐Zinsser Disease in a Patient Following Infection with Sylvatic Epidemic Typhus Associated with Flying Squirrels

et al. 2010

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“…Epidemic typhus flourishes in areas with overcrowding or poor hygiene, such as jails or refugee camps. Although louse control has succeeded in suppressing typhus in the modern era, recent outbreaks in the USA (Reynolds et al, 2003), Africa (Mokrani et al, 2004) and Europe (Tarasevich et al, 1998) have re-established R. prowazekii as a re-emerging disease threat; its potential use in bioterrorism (Radulovic & Azad, 2002) places it in category B of the Biodefense Category A, B and C Priority Pathogens of the National Institute of Allergy and Infectious Diseases.…”

Section: Introductionmentioning

confidence: 99%

Structure of 3-ketoacyl-(acyl-carrier-protein) reductase fromRickettsia prowazekiiat 2.25 Å resolution

et al. 2011

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Rickettsia prowazekii, a parasitic Gram‐negative bacterium, is in the second‐highest biodefense category of pathogens of the National Institute of Allergy and Infectious Diseases, but only a handful of structures have been deposited in the PDB for this bacterium; to date, all of these have been solved by the SSGCID. Owing to its small genome (about 800 protein‐coding genes), it relies on the host for many basic biosynthetic processes, hindering the identification of potential antipathogenic drug targets. However, like many bacteria and plants, its metabolism does depend upon the type II fatty‐acid synthesis (FAS) pathway for lipogenesis, whereas the predominant form of fatty‐acid biosynthesis in humans is via the type I pathway. Here, the structure of the third enzyme in the FAS pathway, 3‐ketoacyl‐(acyl‐carrier‐protein) reductase, is reported at a resolution of 2.25 Å. Its fold is highly similar to those of the existing structures from some well characterized pathogens, such as Mycobacterium tuberculosis and Burkholderia pseudomallei, but differs significantly from the analogous mammalian structure. Hence, drugs known to target the enzymes of pathogenic bacteria may serve as potential leads against Rickettsia, which is responsible for spotted fever and typhus and is found throughout the world.

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“…Recent outbreaks of epidemic typhus underscore the continued menace that this disease maintains (11,12,18). In the United States, R. prowazekii infection of humans has been associated with the existence of a zoonotic reservoir, the flying squirrel (4,16), and serological surveys have identified individuals with antibodies reactive with R. prowazekii in the homeless population in Houston, Texas (14). In addition, R. prowazekii has been designated a category B select agent, raising additional concerns regarding its use as an agent of bioterrorism.…”

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confidence: 99%

Directed Mutagenesis of the Rickettsia prowazekii pld Gene Encoding Phospholipase D

Driskell

Zhang

et al. 2009

Infect Immun

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Rickettsia prowazekii, the causative agent of epidemic typhus, is an obligately intracytoplasmic bacterium, a lifestyle that imposes significant barriers to genetic manipulation. The key to understanding how this unique bacterium evades host immunity is the mutagenesis of selected genes hypothesized to be involved in virulence. The R. prowazekii pld gene, encoding a protein with phospholipase D activity, has been associated with phagosomal escape. To demonstrate the feasibility of site-directed knockout mutagenesis of rickettsial genes and to generate a nonrevertible vaccine strain, we utilized homologous recombination to generate a pld mutant of the virulent R. prowazekii strain Madrid Evir. Using linear DNA for transformation, a double-crossover event resulted in the replacement of the rickettsial wild-type gene with a partially deleted pld gene. Linear DNA was used to prevent potentially revertible single-crossover events resulting in plasmid insertion. Southern blot and PCR analyses were used to confirm the presence of the desired mutation and to demonstrate clonality. While no phenotypic differences were observed between the mutant and wild-type strains when grown in tissue culture, the pld mutant exhibited attenuated virulence in the guinea pig model. In addition, animals immunized with the mutant strain were protected against subsequent challenge with the virulent Breinl strain, suggesting that this transformant could serve as a nonrevertible, attenuated vaccine strain. This study demonstrates the feasibility of generating site-directed rickettsial gene mutants, providing a new tool for understanding rickettsial biology and furthering advances in the prevention of epidemic typhus.

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Flying Squirrel–associated Typhus, United States

Cited by 54 publications

References 12 publications

Brill‐Zinsser Disease in a Patient Following Infection with Sylvatic Epidemic Typhus Associated with Flying Squirrels

Brill‐Zinsser Disease in a Patient Following Infection with Sylvatic Epidemic Typhus Associated with Flying Squirrels

Structure of 3-ketoacyl-(acyl-carrier-protein) reductase fromRickettsia prowazekiiat 2.25 Å resolution

Directed Mutagenesis of the Rickettsia prowazekii pld Gene Encoding Phospholipase D

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