Tick-Borne Emerging Infections

Ismail, Nahed; McBride, Jere W.

doi:10.1016/j.cll.2017.01.006

Cited by 157 publications

(155 citation statements)

References 162 publications

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“…However, in our results, although there was positive PCR amplification for the Anaplasmataceae family, there was no positive PCR amplification specifically for the Ehrlichia genus. The most studied species of this genus are Ehrlichia canis and Ehrlichia chaffeensis (83). In studies that, focused on wildlife, Ehrlichia spp.…”

Section: Tick-borne Associated Pathogensmentioning

confidence: 99%

Ticks and Associated Pathogens From Rescued Wild Animals in Rainforest Fragments of Northeastern Brazil

et al. 2020

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The Ixodidae family comprises ticks that are hematophagous ectoparasites and are considered vectors of several hemoparasites from the Anaplasmataceae family and the genus Hepatozoon, Babesia, and Rickettsia. These ectoparasites parasitize domestic and wild animals belonging to several vertebrate groups. Ticks are highly adapted to different biomes and thus possess a wide geographical distribution. In the Brazilian state of Bahia, localized in the Northeast region, there are large rainforest fragments. Studies have rarely been carried out on ticks, and their hemoparasites, that parasitize wild animals in this region. Thus, this study aimed to identify the tick species parasitizing wild animals rescued in rainforest fragments of Bahia and investigate the presence of hemoparasites in tick tissues. During a 2-year period, 238 ticks were collected from 41 wild mammalians, reptiles, and amphibians. These ectoparasites were taxonomically classified according to their morphological characteristics. The ticks identified belonged to five different species from the Ixodidae family: Amblyomma varium, Amblyomma rotundatum, Amblyomma nodosum, Ixodes loricatus, and Rhipicephalus sanguineus. For the first time, an A. rotundatum parasitizing the Mesoclemmys tuberculata turtle was described. PCR assays using DNA extracted from salivary glands or midgut of the ticks were performed to detect specific DNA fragments of hemoparasites from the genus Rickettsia, Ehrlichia, Babesia, Hepatozoon, and from the Anaplasmataceae family. The results showed positive detection of the Rickettsia genus (7.9%), Anaplasmataceae family (15.8%), and Hepatozoon genus (15.8%). Specific DNA from the Ehrlichia and Babesia genera were not detected in these samples. Specific DNA from members of the Anaplasmataceae family was detected in A. varium for the first time. The present Fonseca et al. Ticks in Wild Animals work showed that amphibians, reptiles, and mammals from Bahia's Atlantic Forest areparasitized by different tick species, and that these ectoparasites present pathogens in their tissues that impact both humans and animals due to their zoonotic potential.

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Section: Tick-borne Associated Pathogensmentioning

confidence: 99%

Ticks and Associated Pathogens From Rescued Wild Animals in Rainforest Fragments of Northeastern Brazil

et al. 2020

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“…Ruminants are the main source for C. burnetii, being responsible for zoonotic outbreaks in several countries (Maurin & Raoult, 1999;Georgiev et al, 2013;OIE, 2018). Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophilic granulocytes, causing tick-borne fever in sheep and cattle, and granulocytic anaplasmosis in dogs, horses, cats, and humans (Dumler et al, 2001;Carrade et al, 2004;Atif, 2015;Ismail & McBride, 2017;Lappin, 2018;Saleem et al, 2018). The main vectors are ticks of the Ixodes complex (I. ricinus, I. scapularis, I. pacificus, I. persulcatus, and I. spinipalpis) (Stuen et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Serological occurrence for tick-borne agents in beef cattle in the Brazilian Pantanal

Ramos

Mello

Mendes

et al. 2020

Rev. Bras. Parasitol. Vet.

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This study investigated the seropositivity for five different tick-borne agents, namely Anaplasma marginale, Babesia bovis, Babesia bigemina, Coxiella burnetii, Anaplasma phagocytophilum, and Trypanosoma vivax in beef cattle in the Brazilian Pantanal. The serum samples collected from animals (200 cows; 200 calves) were used in indirect enzyme-linked immunosorbent assays (iELISA) to detect IgG antibodies against A. marginale, B. bovis, B. bigemina, and T. vivax, and Indirect Fluorescent Antibody Test (IFAT) for detecting IgG antibodies against C. burnetii and A. phagocytophilum. No correlation was observed between seropositivity for C. burnetii and A. phagocytophilum with other agents whereas moderate correlation was observed for A. marginalexB. bigemina x B. bovis. Cows were more seropositive for T. vivax whereas calves were more seropositive for B. bovis and B. bigemina. The highest number of seropositive animals by a single agent was observed for T. vivax (15.2%). Co-seropositivity for T. vivax + A. marginale was higher in cows (25.5%) and for T. vivax + B. bovis + B. bigemina + A. marginale was higher in calves (57.5%). The high seropositivity correlation for A. marginale x B. bovis x B. bigemina is probably due to the presence of the tick biological vector, Rhipicephalus microplus, in the studied farms. Common transmission pathways, mediated by hematophagous dipterans and fomites, may explain the high co-seropositivity of cows for A. marginale and T. vivax. Low seropositivity to C. burnetii is probably due to the type of breeding system employed (extensive). Seropositivity for A. phagocytophilum in only one animal suggests the occurrence of a cross-serological reaction with another agent of the genus Anaplasma.

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“…Mechanistic insights yielded by such studies can benefit the development of novel strategies for treating and preventing infection. Anaplasma phagocytophilum is an Ixodes species ticktransmitted obligate intracellular bacterium that infects neutrophils to cause the emerging zoonosis known as granulocytic anaplasmosis in humans and some domestic animals (1,2). Human granulocytic anaplasmosis (HGA) can also be transmitted perinatally, via blood transfusion, and possibly, by exposure to infected blood (3)(4)(5)(6)(7)(8).…”

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confidence: 99%

“…HGA manifestations include fever, chills, headache, malaise, leukopenia, thrombocytopenia, and elevated serum levels of liver enzymes. Complications can include seizures, pneumonitis, rhabdomyolysis, hemorrhage, shock, increased susceptibility to secondary infections, and death (1,2). HGA occurs predominantly in northeastern and upper Midwestern states, although its geographic range is expanding (9).…”

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confidence: 99%

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Binding of Host Cell Surface Protein Disulfide Isomerase by Anaplasma phagocytophilum Asp14 Enables Pathogen Infection

Green

Naimi

Oliver

et al. 2020

mBio

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Diverse intracellular pathogens rely on eukaryotic cell surface disulfide reductases to invade host cells. Pharmacologic inhibition of these enzymes is cytotoxic, making it impractical for treatment. Identifying and mechanistically dissecting microbial proteins that co-opt surface reductases could reveal novel targets for disrupting this common infection strategy. Anaplasma phagocytophilum invades neutrophils by an incompletely defined mechanism to cause the potentially fatal disease granulocytic anaplasmosis. The bacterium’s adhesin, Asp14, contributes to invasion by virtue of its C terminus engaging an unknown receptor. Yeast-two hybrid analysis identified protein disulfide isomerase (PDI) as an Asp14 binding partner. Coimmunoprecipitation confirmed the interaction and validated it to be Asp14 C terminus dependent. PDI knockdown and antibody-mediated inhibition of PDI reductase activity impaired A. phagocytophilum infection of but not binding to host cells. Infection during PDI inhibition was rescued when the bacterial but not host cell surface disulfide bonds were chemically reduced with tris(2-carboxyethyl)phosphine-HCl (TCEP). TCEP also restored bacterial infectivity in the presence of an Asp14 C terminus blocking antibody that otherwise inhibits infection. A. phagocytophilum failed to productively infect myeloid-specific-PDI conditional-knockout mice, marking the first demonstration of in vivo microbial dependency on PDI for infection. Mutational analyses identified the Asp14 C-terminal residues that are critical for binding PDI. Thus, Asp14 binds and brings PDI proximal to A. phagocytophilum surface disulfide bonds that it reduces, which enables cellular and in vivo infection. IMPORTANCE Anaplasma phagocytophilum infects neutrophils to cause granulocytic anaplasmosis, an emerging potentially fatal disease and the second-most common tick-borne illness in the United States. Treatment options are limited, and no vaccine exists. Due to the bacterium’s obligatory intracellular lifestyle, A. phagocytophilum survival and pathogenesis are predicated on its ability to enter host cells. Understanding its invasion mechanism will yield new targets for preventing bacterial entry and, hence, disease. We report a novel entry pathway in which the A. phagocytophilum outer membrane protein Asp14 binds host cell surface protein disulfide isomerase via specific C-terminal residues to promote reduction of bacterial surface disulfide bonds, which is critical for cellular invasion and productive infection in vivo. Targeting the Asp14 C terminus could be used to prevent/treat granulocytic anaplasmosis. Our findings have broad implications, as a thematically similar approach could be applied to block infection by other intracellular microbes that exploit cell surface reductases.

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Tick-Borne Emerging Infections

Cited by 157 publications

References 162 publications

Ticks and Associated Pathogens From Rescued Wild Animals in Rainforest Fragments of Northeastern Brazil

Ticks and Associated Pathogens From Rescued Wild Animals in Rainforest Fragments of Northeastern Brazil

Serological occurrence for tick-borne agents in beef cattle in the Brazilian Pantanal

Binding of Host Cell Surface Protein Disulfide Isomerase by Anaplasma phagocytophilum Asp14 Enables Pathogen Infection

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