Rickettsiosis Caused by Rickettsia parkeri, Mexico

AbstractThe rickettsiae are obligate intracellular alphaproteobacteria that exhibit a complex infectious life cycle in both arthropod and mammalian hosts. As obligate intracellular bacteria,Rickettsiaare highly adapted to living inside a variety of host cells, including vascular endothelial cells during mammalian infection. Although it is assumed that the rickettsiae produce numerous virulence factors that usurp or disrupt various host cell pathways, they have been challenging to genetically manipulate to identify the key bacterial factors that contribute to infection. Motivated to overcome this challenge, we sought to expand the repertoire of available rickettsial loss-of-function mutants, using an improvedmariner-based transposon mutagenesis scheme. Here, we present the isolation of over 100 transposon mutants in the spotted fever group speciesRickettsia parkeri. These mutants targeted genes implicated in a variety of pathways, including bacterial replication and metabolism, hypothetical proteins, the type IV secretion system, as well as factors with previously established roles in host cell interactions and pathogenesis. Given the need to identify critical virulence factors, forward genetic screens such as this will provide an excellent platform to more directly investigate rickettsial biology and pathogenesis.

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A metabolic dependency for host isoprenoids in the obligate intracellular pathogenRickettsia parkeriunderlies a sensitivity for the statin class of host-targeted therapeutics

10.1101/528018 ◽

2019 ◽

Cited By ~ 1

Author(s):

Vida Ahyong ◽

Charles A. Berdan ◽

Daniel K. Nomura ◽

Matthew D. Welch

Keyword(s):

Cell Wall ◽

Host Cell ◽

Bacterial Growth ◽

Spotted Fever ◽

Intracellular Pathogens ◽

Biosynthetic Pathways ◽

Targeted Therapeutics ◽

Rickettsia Parkeri ◽

Obligate Intracellular ◽

Intracellular Parasites

AbstractGram-negative bacteria in the order Rickettsiales are obligate intracellular parasites that cause human diseases such typhus and spotted fever. They have evolved a dependence on essential nutrients and metabolites from the host cell as a consequence of extensive genome streamlining. However, it remains largely unknown which nutrients they require and whether their metabolic dependency can be exploited therapeutically. Here, we describe a genetic rewiring of bacterial isoprenoid biosynthetic pathways in the Rickettsiales that has resulted from reductive genome evolution. We further investigated whether the spotted fever groupRickettsiaspeciesRickettsia parkeriscavenges isoprenoid precursors directly from the host. Using targeted mass spectrometry in uninfected and infected cells, we found decreases in host isoprenoid products and concomitant increases in bacterial isoprenoid metabolites. Additionally, we report that bacterial growth is prohibited by inhibition of the host isoprenoid pathway with the statins class of drugs. We show that growth inhibition correlates with changes in bacterial size and shape that mimic those caused by antibiotics that inhibit peptidoglycan biosynthesis, suggesting statins inhibit cell wall synthesis. Altogether, our results describe an Achilles’ heel of obligate intracellular pathogens that can be exploited with host-targeted therapeutics that interfere with metabolic pathways required for bacterial growth.ImportanceObligate intracellular parasites, which include viruses as well as certain bacteria and eukaryotes, extract essential nutrients and metabolites from their host cell. As a result, these pathogens have often lost essential biosynthetic pathways and are metabolically dependent on the host. In this study, we describe a metabolic dependency of the bacterial pathogenRickettsia parkerion host isoprenoid molecules that are used in the biosynthesis of downstream products including cholesterol, steroid hormones, and heme. Bacteria make products from isoprenoids such as an essential lipid carrier for making the bacterial cell wall. We show that bacterial metabolic dependency can represent an Achilles’ heel, and that inhibiting host isoprenoid biosynthesis with the FDA-approved statin class of drugs inhibits bacterial growth by interfering with the integrity of the cell wall. This work highlights a potential to treat infections by obligate intracellular pathogens through inhibition of host biosynthetic pathways that are susceptible to parasitism.

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Serological evidence of Rickettsia parkeri as the etiological agent of rickettsiosis in Uruguay

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652009000600005 ◽

2009 ◽

Vol 51 (6) ◽

pp. 337-339 ◽

Cited By ~ 25

Author(s):

Ismael A. Conti-Díaz ◽

Jonas Moraes-Filho ◽

Richard C. Pacheco ◽

Marcelo B. Labruna

Keyword(s):

Spotted Fever ◽

Clinical Manifestations ◽

The United States ◽

Immunofluorescence Assay ◽

Etiological Agent ◽

Serological Evidence ◽

Rickettsia Parkeri ◽

Rickettsia Rickettsii ◽

Antibody Absorption ◽

Mild Fever

We report three new rickettsiosis human cases in Uruguay. The three clinical cases presented clinical manifestations similar to previous reported cases of Rickettsia parkeri in the United States; that is mild fever (< 40 ºC), malaise, headache, rash, inoculation eschar at the tick bite site, regional lymphadenopathy, and no lethality. Serological antibody-absorption tests with purified antigens of R. parkeri and Rickettsia rickettsii, associated with immunofluorescence assay indicated that the patients in two cases were infected by R. parkeri. Epidemiological and clinical evidences, coupled with our serological analysis, suggest that R. parkeri is the etiological agent of human cases of spotted fever in Uruguay, a disease that has been recognized in that country as cutaneous-ganglionar rickettsiosis.

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The rice rat Euryoryzomys russatus, a competent amplifying host of Rickettsia parkeri strain Atlantic rainforest for the tick Amblyomma ovale

Ticks and Tick-borne Diseases ◽

10.1016/j.ttbdis.2018.04.013 ◽

2018 ◽

Vol 9 (5) ◽

pp. 1133-1136 ◽

Cited By ~ 4

Author(s):

Felipe S. Krawczak ◽

Marcelo B. Labruna

Keyword(s):

Atlantic Rainforest ◽

Rickettsia Parkeri ◽

Amblyomma Ovale

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What Is Going on With the Genus Dermacentor? Hybridizations, Introgressions, Oh My!

Journal of Medical Entomology ◽

10.1093/jme/tjz219 ◽

2019 ◽

Vol 57 (3) ◽

pp. 653-656 ◽

Cited By ~ 2

Author(s):

Jerome Goddard ◽

Michelle Allerdice ◽

J Santos Portugal ◽

Gail M Moraru ◽

Christopher D Paddock ◽

...

Keyword(s):

Genetic Material ◽

Single Species ◽

Dermacentor Variabilis ◽

Species Concepts ◽

Rickettsia Parkeri ◽

Public Health Perspective ◽

Dermacentor Andersoni ◽

Rickettsia Rickettsii ◽

Close Relationship ◽

Specific Species

Abstract In the 1930s, R. A. Cooley noted that Dermacentor occidentalis (Acarina: Ixodidae) and Dermacentor andersoni were closely related and could hybridize. Decades later, James Oliver discovered that crosses of Dermacentor variabilis, D. andersoni, and D. occidentalis could, on occasion, produce hybrids. A recent molecular analysis (both mtDNA and nDNA) in our laboratory revealed that certain specimens of Dermacentor andersoni nested with Dermacentor parumapertus. Does this close relationship, along with the mito-nuclear discordance we have observed, mean D. andersoni and D. parumapertus are a single species? By contemporary taxonomic criteria, this seems improbable based on their distinctly different morphologies, host associations, and ecologies. This paper explores ideas related to mito-nuclear discordance, hybridization, and introgression (primarily) not only in these two species but also other members of the genus Dermacentor. Both D. andersoni and D. parumapertus can be found on the same hosts and have sympatric distributions, so introgression of genetic material by occasional cross-mating between these two species is possible. Further, the difficulty in applying specific species concepts in ticks has been recently pointed out and a unified agreement on an integrative species concepts could clearly be useful in this situation. With the discovery of D. parumapertus as a potential vector of Rickettsia parkeri and the historically recognized role of D. andersoni in transmission of Rickettsia rickettsii, understanding the specific status of each lineage of these species (and others in the genus) is extremely important from a public health perspective.

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Infección por rickettsia en capibaras (Hydrochoerus hydrochaeris) de São Paulo, Brasil: evidencia serológica de infección por Rickettsia bellii y Rickettsia parkeri

Biomédica ◽

10.7705/biomedica.v27i3.199 ◽

2007 ◽

Vol 27 (3) ◽

pp. 364 ◽

Cited By ~ 37

Author(s):

Richard C. Pacheco ◽

Mauricio C. Horta ◽

Jonas Moraes-Filho ◽

Alexandre C. Ataliba ◽

Adriano Pinter ◽

...

Keyword(s):

Sao Paulo ◽

São Paulo ◽

Rickettsia Parkeri ◽

Hydrochoerus Hydrochaeris ◽

Rickettsia Bellii

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Comparative Evaluation of Infected and NoninfectedAmblyomma tristeTicks withRickettsia parkeri, the Agent of an Emerging Rickettsiosis in the New World

BioMed Research International ◽

10.1155/2013/402737 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

F. A. Nieri-Bastos ◽

M. P. J. Szabó ◽

R. C. Pacheco ◽

J. F. Soares ◽

H. S. Soares ◽

...

Keyword(s):

Infected Group ◽

Control Group ◽

Control Groups ◽

Rickettsia Parkeri ◽

Amblyomma Triste ◽

Vertebrate Hosts ◽

Domestic Rabbits ◽

And Control ◽

Term Maintenance

The distribution ofRickettsia parkeriin South America has been associated withAmblyomma tristeticks. The present study evaluated under laboratory conditions two colonies ofA. triste: one started from engorged females that were naturally infected byR. parkeri(designated as infected group); the other started from noninfected females (designated as control group). Both colonies were reared in parallel for five consecutive generations. Tick-naïve domestic rabbits were used for feeding of each tick stage and generation.R. parkeriwas preserved by transstadial maintenance and transovarial transmission inA. tristeticks for five consecutive generations, because all tested larvae, nymphs, and adults from the infected group were shown by PCR to contain rickettsial DNA. All rabbits infested by larvae, nymphs, and adults from the infected group seroconverted, indicating that these tick stages were all vector competent forR. parkeri. Expressive differences in mortality rates were observed between engorged nymphs from the infected and control groups, as indicated by 65.9% and 92.4% molting success, respectively. Our results indicate thatA. tristecan act as a natural reservoir forR. parkeri. However, due to deleterious effect caused byR. parkerion engorged nymphs, amplifier vertebrate hosts might be necessary for natural long-term maintenance ofR. parkeriinA. triste.

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