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1.
J Proteomics ; 254: 104476, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34990822

RESUMO

Over the last 20 years, advances in sequencing technologies paired with biochemical and structural studies have shed light on the unique pharmacological arsenal produced by the salivary glands of hematophagous arthropods that can target host hemostasis and immune response, favoring blood acquisition and, in several cases, enhancing pathogen transmission. Here we provide a deeper insight into Xenopsylla cheopis salivary gland contents pairing transcriptomic and proteomic approaches. Sequencing of 99 pairs of salivary glands from adult female X. cheopis yielded a total of 7432 coding sequences functionally classified into 25 classes, of which the secreted protein class was the largest. The translated transcripts also served as a reference database for the proteomic study, which identified peptides from 610 different proteins. Both approaches revealed that the acid phosphatase family is the most abundant salivary protein group from X. cheopis. Additionally, we report here novel sequences similar to the FS-H family, apyrases, odorant and hormone-binding proteins, antigen 5-like proteins, adenosine deaminases, peptidase inhibitors from different subfamilies, proteins rich in Glu, Gly, and Pro residues, and several potential secreted proteins with unknown function. SIGNIFICANCE: The rat flea X. cheopis is the main vector of Yersinia pestis, the etiological agent of the bubonic plague responsible for three major pandemics that marked human history and remains a burden to human health. In addition to Y. pestis fleas can also transmit other medically relevant pathogens including Rickettsia spp. and Bartonella spp. The studies of salivary proteins from other hematophagous vectors highlighted the importance of such molecules for blood acquisition and pathogen transmission. However, despite the historical and clinical importance of X. cheopis little is known regarding their salivary gland contents and potential activities. Here we provide a comprehensive analysis of X. cheopis salivary composition using next generation sequencing methods paired with LC-MS/MS analysis, revealing its unique composition compared to the sialomes of other blood-feeding arthropods, and highlighting the different pathways taken during the evolution of salivary gland concoctions. In the absence of the X. cheopis genome sequence, this work serves as an extended reference for the identification of potential pharmacological proteins and peptides present in flea saliva.


Assuntos
Sifonápteros , Xenopsylla , Animais , Cromatografia Líquida , Feminino , Insetos Vetores , Proteômica , Ratos , Sifonápteros/microbiologia , Sifonápteros/fisiologia , Espectrometria de Massas em Tandem , Xenopsylla/genética , Xenopsylla/microbiologia
2.
Insect Sci ; 29(2): 567-580, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34048132

RESUMO

We investigated the performance trade-offs of fleas (Siphonaptera) while adapting to a novel host using two host generalists (Xenopsylla conformis and Xenopsylla ramesis) and one host specialist (Parapulex chephrenis) maintained on their principal hosts (Meriones crassus for Xenopsylla and Acomys cahirinus for P. chephrenis). We asked whether, over generations, (i) a host generalist may become a specialist by evolving the ability to exploit a novel host and losing the ability to exploit an original host and (ii) a host specialist can become a generalist by evolving the ability to exploit a novel host without losing the ability to exploit an original host. We established an experimental line of each species on a novel host (Acomys russatus for Xenopsylla and M. crassus for P. chephrenis) and maintained this line on this host during 23 generations. We compared reproductive performance of progenitors of each line and their descendants when they exploited either original or novel host in terms of egg number and size, hatching success, offspring production, and offspring size. We found changes in performance over generations in female offspring size only. Xenopsylla conformis demonstrated a tendency to become a host specialist (increased performance on the novel host with a concomitant decreased performance on the original host), whereas P. chephrenis demonstrated a tendency to become a host generalist (increased performance on the novel host without a concomitant decreased performance on the original host). We conclude that the probability of generalist to specialist transition, and vice versa, is context-dependent and varies between species.


Assuntos
Infestações por Pulgas , Doenças dos Roedores , Sifonápteros , Xenopsylla , Animais , Feminino , Infestações por Pulgas/parasitologia , Infestações por Pulgas/veterinária , Gerbillinae/parasitologia , Interações Hospedeiro-Parasita
3.
J Biol Chem ; 298(1): 101497, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34919963

RESUMO

The Kv1.3 channel has been widely demonstrated to play crucial roles in the activation and proliferation of T cells, which suggests that selective blockers could serve as potential therapeutics for autoimmune diseases mediated by T cells. We previously described that the toxin mimic FS48 from salivary gland of Xenopsylla cheopis downregulates the secretion of proinflammatory factors by Raw 264.7 cells by blocking the Kv1.3 channel and the subsequent inactivation of the proinflammatory MAPK/NF-κB pathways. However, the effects of FS48 on human T cells and autoimmune diseases are unclear. Here, we described its immunomodulatory effects on human T cells derived from suppression of Kv1.3 channel. Kv1.3 currents in Jurkat T cells were recorded by whole-cell patch-clamp, and Ca2+ influx, cell proliferation, and TNF-α and IL-2 secretion were measured using Fluo-4, CCK-8, and ELISA assays, respectively. The in vivo immunosuppressive activity of FS48 was evaluated with a rat DTH model. We found that FS48 reduced Kv1.3 currents in Jurkat T cells in a concentration-dependent manner with an IC50 value of about 1.42 µM. FS48 also significantly suppressed Kv1.3 protein expression, Ca2+ influx, MAPK/NF-κB/NFATc1 pathway activation, and TNF-α and IL-2 production in activated Jurkat T cells. Finally, we show that FS48 relieved the DTH response in rats. We therefore conclude that FS48 can block the Kv1.3 channel and inhibit human T cell activation, which most likely contributes to its immunomodulatory actions and highlights the great potential of this evolutionary-guided peptide as a drug template in future studies.


Assuntos
Doenças Autoimunes , Canal de Potássio Kv1.3 , Venenos de Escorpião , Linfócitos T , Xenopsylla , Adjuvantes Imunológicos/farmacologia , Animais , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Humanos , Fatores Imunológicos/farmacologia , Interleucina-2/metabolismo , Canal de Potássio Kv1.3/imunologia , Ativação Linfocitária/efeitos dos fármacos , NF-kappa B/metabolismo , Bloqueadores dos Canais de Potássio/imunologia , Ratos , Glândulas Salivares/química , Venenos de Escorpião/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/imunologia , Xenopsylla/química
4.
J Biol Chem ; 297(5): 101322, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34688666

RESUMO

The salivary glands of the flea Xenopsylla cheopis, a vector of the plague bacterium, Yersinia pestis, express proteins and peptides thought to target the hemostatic and inflammatory systems of its mammalian hosts. Past transcriptomic analyses of salivary gland tissue revealed the presence of two similar peptides (XC-42 and XC-43) having no extensive similarities to any other deposited sequences. Here we show that these peptides specifically inhibit coagulation of plasma and the amidolytic activity of α-thrombin. XC-43, the smaller of the two peptides, is a fast, tight-binding inhibitor of thrombin with a dissociation constant of less than 10 pM. XC-42 exhibits similar selectivity as well as kinetic and binding properties. The crystal structure of XC-43 in complex with thrombin shows that despite its substrate-like binding mode, XC-43 is not detectably cleaved by thrombin and that it interacts with the thrombin surface from the enzyme catalytic site through the fibrinogen-binding exosite I. The low rate of hydrolysis was verified in solution experiments with XC-43, which show the substrate to be largely intact after 2 h of incubation with thrombin at 37 °C. The low rate of XC-43 cleavage by thrombin may be attributable to specific changes in the catalytic triad observable in the crystal structure of the complex or to extensive interactions in the prime sites that may stabilize the binding of cleavage products. Based on the increased arterial occlusion time, tail bleeding time, and blood coagulation parameters in rat models of thrombosis XC-43 could be valuable as an anticoagulant.


Assuntos
Anticoagulantes/química , Antitrombinas/química , Proteínas de Insetos/química , Glândulas Salivares/química , Proteínas e Peptídeos Salivares/química , Trombina , Xenopsylla/química , Animais , Humanos , Ratos , Trombina/antagonistas & inibidores , Trombina/química , Xenopsylla/metabolismo
5.
ACS Infect Dis ; 7(8): 2536-2545, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34319069

RESUMO

Fleas are major vectors of Yersinia pestis, the causative agent of plague. It has been proposed that Y. pestis has developed the ability to overcome the innate immune responses of fleas. Despite the fact that they transmit a number of bacterial infections, very little is known about the immune responses in fleas. In this study, we describe the antimicrobial activities of a cecropin from Xenopsylla cheopis (cheopin), an efficient vector for Y. pestis in the wild. This is the first cecropin-class antimicrobial peptide described from Siphonaptera insects. Cheopin showed potent activity against Gram-negative bacteria but little activity against wild-type Y. pestis KIM6+. Deletion of the aminoarabinose operon, which is responsible for the 4-amino-4-deoxy-l-arabinose (Ara4N) modification of LPS, rendered Y. pestis highly susceptible to cheopin. Confocal microscopy and whole cell binding assays indicated that Ara4N modification reduces the affinity of cheopin for Y. pestis. Further, cheopin only permeabilized bacterial membranes in the absence of Ara4N-modified LPS, which was correlated with bacterial killing. This study provides insights into innate immunity of the flea and evidence for the crucial role of Ara4N modification of Y. pestis LPS in conferring resistance against flea antimicrobial peptides.


Assuntos
Cecropinas , Xenopsylla , Yersinia pestis , Animais , Insetos Vetores , Lipopolissacarídeos , Yersinia pestis/genética
6.
J Parasitol ; 107(2): 289-294, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33844840

RESUMO

Members of the flea family Pulicidae have been the focus of many studies due to their significance as diseases vectors of medical and veterinary importance and their cosmopolitan distribution. They often exhibit variation in morphological features that can make correct species identification and management challenging. This may also apply to Xenopsylla brasiliensis (Baker, 1904), an important plague vector. In the current study, we aimed to provide genetic tools for reliable species identification using a DNA barcoding approach. A total of 73 flea specimens was collected from a native host (Namaqua rock mouse, Micaelamys namaquensis) in South Africa and identified morphologically. In addition, we took measurements of 7 morphological characteristics. Subsequently, we successfully generated barcodes of the mitochondrial cytochrome c oxidase subunit I (COI) gene for X. brasiliensis. We validated this approach by comparing our data to COI sequences from Rwandan X. brasiliensis. While sequences from both regions suggested a close relationship between the 2 X. brasiliensis populations, both haplotype and nucleotide diversity were substantially larger for the South African specimens. This may be attributed to human-assisted spread, differences in habitat, and/or host species sampled and merits further study in the future.


Assuntos
Insetos Vetores/anatomia & histologia , Insetos Vetores/genética , Peste/transmissão , Xenopsylla/anatomia & histologia , Xenopsylla/genética , Animais , Código de Barras de DNA Taxonômico , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Infestações por Pulgas/parasitologia , Infestações por Pulgas/veterinária , Variação Genética , Haplótipos , Masculino , Mitocôndrias/enzimologia , Murinae/parasitologia , África do Sul
7.
J Biol Chem ; 296: 100670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33864815

RESUMO

The voltage-gated potassium (Kv) 1.3 channel plays a crucial role in the immune responsiveness of T-lymphocytes and macrophages, presenting a potential target for treatment of immune- and inflammation related-diseases. FS48, a protein from the rodent flea Xenopsylla cheopis, shares the three disulfide bond feature of scorpion toxins. However, its three-dimensional structure and biological function are still unclear. In the present study, the structure of FS48 was evaluated by circular dichroism and homology modeling. We also described its in vitro ion channel activity using patch clamp recording and investigated its anti-inflammatory activity in LPS-induced Raw 264.7 macrophage cells and carrageenan-induced paw edema in mice. FS48 was found to adopt a common αßß structure and contain an atypical dyad motif. It dose-dependently exhibited the Kv1.3 channel in Raw 264.7 and HEK 293T cells, and its ability to block the channel pore was demonstrated by the kinetics of activation and competition binding with tetraethylammonium. FS48 also downregulated the secretion of proinflammatory molecules NO, IL-1ß, TNF-α, and IL-6 by Raw 264.7 cells in a manner dependent on Kv1.3 channel blockage and the subsequent inactivation of the MAPK/NF-κB pathways. Finally, we observed that FS48 inhibited the paw edema formation, tissue myeloperoxidase activity, and inflammatory cell infiltrations in carrageenan-treated mice. We therefore conclude that FS48 identified from the flea saliva is a novel potassium channel inhibitor displaying anti-inflammatory activity. This discovery will promote understanding of the bloodsucking mechanism of the flea and provide a new template molecule for the design of Kv1.3 channel blockers.


Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Canal de Potássio Kv1.3/antagonistas & inibidores , Macrófagos/efeitos dos fármacos , Glândulas Salivares/metabolismo , Venenos de Escorpião/química , Animais , Edema/imunologia , Edema/metabolismo , Edema/patologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , NF-kappa B/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Xenopsylla
8.
PLoS Negl Trop Dis ; 15(2): e0009029, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33600454

RESUMO

Murine typhus is a flea-borne zoonotic disease that has been recently reported on Reunion Island, an oceanic volcanic island located in the Indian Ocean. Five years of survey implemented by the regional public health services have highlighted a strong temporal and spatial structure of the disease in humans, with cases mainly reported during the humid season and restricted to the dry southern and western portions of the island. We explored the environmental component of this zoonosis in an attempt to decipher the drivers of disease transmission. To do so, we used data from a previously published study (599 small mammals and 175 Xenopsylla fleas from 29 sampling sites) in order to model the spatial distribution of rat fleas throughout the island. In addition, we carried out a longitudinal sampling of rats and their ectoparasites over a 12 months period in six study sites (564 rats and 496 Xenopsylla fleas) in order to model the temporal dynamics of flea infestation of rats. Generalized Linear Models and Support Vector Machine classifiers were developed to model the Xenopsylla Genus Flea Index (GFI) from climatic and environmental variables. Results showed that the spatial distribution and the temporal dynamics of fleas, estimated through the GFI variations, are both strongly controlled by abiotic factors: rainfall, temperature and land cover. The models allowed linking flea abundance trends with murine typhus incidence rates. Flea infestation in rats peaked at the end of the dry season, corresponding to hot and dry conditions, before dropping sharply. This peak of maximal flea abundance preceded the annual peak of human murine typhus cases by a few weeks. Altogether, presented data raise novel questions regarding the ecology of rat fleas while developed models contribute to the design of control measures adapted to each micro region of the island with the aim of lowering the incidence of flea-borne diseases.


Assuntos
Infestações por Pulgas/veterinária , Ratos/parasitologia , Tifo Endêmico Transmitido por Pulgas/epidemiologia , Xenopsylla , Animais , Ecossistema , Infestações por Pulgas/epidemiologia , Humanos , Incidência , Mamíferos/parasitologia , Reunião/epidemiologia , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/parasitologia , Estações do Ano , Análise Espaço-Temporal , Tifo Endêmico Transmitido por Pulgas/transmissão
9.
Parasit Vectors ; 14(1): 24, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407807

RESUMO

BACKGROUND: The endemic rodent family of Bathyergidae in Africa, particularly South Africa, are understudied as reservoirs of diseases of significant medical importance. Considering the diversity and wide distribution of African mole-rats in South Africa, many of these bathyergids could act as carriers of zoonoses. METHODS: The present study assessed the ectoparasite community of the Mahali mole-rat (Cryptomys hottentotus mahali). We aimed to identify possible parasitic arthropods that may infest this mole-rat species and explore host preference, contributions of seasonality, host sex and body mass as well as social class and colony size on ectoparasite assemblage prevalence and abundance. RESULTS: A limited number of ectoparasite species were found on C. h. mahali belonging to two significant taxa: mites (Acari) and fleas, with mites being the most prevalent and abundant. We recorded the presence of X. philoxera, a flea well known as the principal reservoir of plague in the southern African region on the Mahali mole-rats. Only three mite species were collected: Androlaelaps scapularis, Androlaelaps capensis and Laelaps liberiensis. Seasonal peaks in prevalence and abundance of X. philoxera and A. scapularis were observed during summer. Xenopsylla philoxera abundance and A. scapularis loads significantly increased on reproductive mole-rat individuals in comparison to non-reproductive individuals. CONCLUSION: Despite the wide distribution of the subterranean African mole-rats, studies investigating their parasitic fauna remain limited and scarce. This dearth in knowledge raises the concern regarding their potential role as an endemic reservoir for zoonotic diseases. Consequently, additional sampling of their ectoparasitic community throughout their distributional range and research addressing their role as a reservoir for zoonotic diseases in southern Africa are urgently needed.


Assuntos
Ectoparasitoses/parasitologia , Ratos-Toupeira/parasitologia , África Austral/epidemiologia , Animais , Vetores Artrópodes , Artrópodes , Vetores de Doenças , Ectoparasitoses/transmissão , Ácaros , Ftirápteros , Peste/transmissão , Prevalência , Doenças dos Roedores/parasitologia , Doenças dos Roedores/transmissão , Estações do Ano , Sifonápteros/microbiologia , Xenopsylla/microbiologia , Zoonoses
10.
Parasitol Res ; 120(2): 451-459, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33447886

RESUMO

We studied the success of fleas, Synosternus cleopatrae and Xenopsylla ramesis, in switching to a novel host by establishing experimental lines maintained on different hosts for 18 generations. Fleas fed on principal (P-line) or novel hosts, either sympatric with (S-line) or allopatric to (A-line) a flea and its principal host, then we assessed their reproductive performance via the number and size of eggs. We compared reproductive performance between hosts within a line and between lines within a host asking: (a) whether fleas adapt to a novel host species after multiple generations; (b) if yes, whether the pattern of adaptation differs between novel host species sympatric with or allopatric to a flea and its principal host; and (c) adaptation to a novel host is accompanied with a loss of success in exploitation of an original host. Fleas from the S- and A-lines increased their egg production on a novel host (except X. ramesis from the S-line). S. cleopatrae from the S-line but not the A-line increased egg size on a novel host, whereas X. ramesis from the A-line but not the S-line produced larger eggs from a novel host. We found no indication of a loss of reproductive performance on the original host while adapting to a novel host. We conclude that fleas are able to switch rapidly to a new host with the pattern of a switch to either sympatric or an allopatric host depending on the identities of both flea and host species.


Assuntos
Infestações por Pulgas/parasitologia , Sifonápteros/fisiologia , Animais , Feminino , Especificidade de Hospedeiro , Interações Hospedeiro-Parasita , Masculino , Óvulo/citologia , Óvulo/fisiologia , Reprodução/fisiologia , Sifonápteros/classificação , Xenopsylla/fisiologia
11.
J Vector Ecol ; 45(2): 333-355, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33207051

RESUMO

Rattus rattus was first reported from the West Nile Region of Uganda in 1961, an event that preceded the appearance of the first documented human plague outbreak in 1970. We investigated how invasive R. rattus and native small mammal populations, as well as their fleas, have changed in recent decades. Over an 18-month period, a total of 2,959 small mammals were captured, sampled, and examined for fleas, resulting in the identification of 20 small mammal taxa that were hosts to 5,109 fleas (nine species). Over three-fourths (75.8%) of captured mammals belonged to four taxa: R. rattus, which predominated inside huts, and Arvicanthis niloticus, Mastomys sp., and Crocidura sp., which were more common outside huts. These mammals were hosts for 85.8% of fleas collected, including the efficient plague vectors Xenopsylla cheopis and X. brasiliensis, as well as likely enzootic vectors, Dinopsyllus lypusus and Ctenophthalmus bacopus. Flea loads on small mammals were higher in certain environments in villages with a recent history of plague compared to those that lacked such a history. The significance of these results is discussed in relation to historical data, the initial spread of plague in the WNR and the continuing threat posed by the disease.


Assuntos
Insetos Vetores , Murinae/parasitologia , Peste/transmissão , Musaranhos/parasitologia , Xenopsylla , Animais , Infestações por Pulgas , Humanos , Ratos , Uganda
12.
J Vector Ecol ; 45(2): 254-261, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33207054

RESUMO

Because isolated ecosystems contribute to species variability, especially oceanic island ecosystems, the present work focused on the study of the Bartonella species and haplotypes in Lanzarote and El Hierro, two Canary islands with evident bioclimatic differences between them. A total of 123 rodents and 110 fleas from two islands were screened for the presence of Bartonella by PCR analysis of the gltA and nuoG genes. The overall prevalence was 5.7% in rodents and 20.4% in fleas. A total of seven gltA-haplotypes was found in both rodents and fleas, belonging to the species Bartonella mastomydis and Bartonella tribocorum in Lanzarote, and to Bartonella rochalimae and Bartonella elizabethae in El Hierro, as well as recently described species Bartonella kosoyi in both islands. Besides, potential co-infections were detected based on the nuoG analysis. Further, Xenopsylla cheopis was the only flea species identified. Our study shows that isolated ecosystems such as the Canary Islands lead to the appearance of new Bartonella haplotypes along different biotopes, with diverse flea species involved in the spreading of the pathogen being of great relevance due to the zoonotic potential of the species found.


Assuntos
Bartonella/genética , Bartonella/isolamento & purificação , Camundongos/parasitologia , Ratos/parasitologia , Xenopsylla/microbiologia , Animais , Haplótipos , Insetos Vetores , Filogenia , Espanha
13.
J Vector Ecol ; 45(2): 241-253, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33207059

RESUMO

The objective of this study was to investigate evidence of emerging anaplasmosis and bartonellosis in rodents from endemic areas of Nakhon Ratchasima, Thailand. Rodent trapping was undertaken in 13 sub-districts of Muang District. The live-capture traps were set up in three locations of selected scrub typhus patient houses for three consecutive nights. Wild-caught rodent whole blood samples and associated ticks and fleas were collected and tested for Anaplasma spp. and Bartonella spp. In addition, heat maps using GIS software were used to determine the density of infection of positive wild-caught rodents. A total of 347 wild-caught rodents of nine species was captured. Rattus rattus (38.6%) was the dominant species. A total of 1,518 Heamaphysalis bandicota ticks and 57 Xenopsylla cheopis fleas was removed. Twenty-two of the 347 tested blood samples (6.3%) were Anaplasma bovis-positive and 121 blood samples and five out of 27 pools of X. cheopis fleas were Bartonella queenslandensis-positive. Of these infected rodents, dual-infections between A. bovis and B. queenslandensis were found in three B. indica rodents. Our results offer new information concerning the infections of A. bovis and B. queenslandensis in both rodents and their ectoparasites collected in high-risk areas of rodent-borne diseases in Thailand.


Assuntos
Anaplasma/isolamento & purificação , Bartonella/isolamento & purificação , Ixodidae/microbiologia , Murinae/parasitologia , Xenopsylla/microbiologia , Anaplasmose/transmissão , Animais , Infecções por Bartonella/transmissão , Insetos Vetores/microbiologia
14.
Cutis ; 106(3): 124-126, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33104121

RESUMO

The oriental rat flea (Xenopsylla cheopis) is an ectoparasite of small mammals and a vector of many diseases for which humans are incidental hosts. This species of flea is most widely known for carrying Yersinia pestis and Rickettsia typhi, the causative agents of the plague and murine typhus, respectively. Public health issues related to X cheopis may increase in the future as global warming expands the geographic area in which the fleas can survive. A bioterrorist attack of plague also remains a threat. Extensive research is ongoing regarding X cheopis and its interaction with the bacteria it transmits to find better ways of reducing related morbidity and mortality. Traditional control measures include extermination of small mammal hosts, insecticide use to eliminate the flea itself, and use of antibiotics to control the associated diseases. The future may include targeted insecticide usage to prevent the continued development of resistance as well as new methods of reducing transmission of flea-borne diseases that could eliminate the need for chemical insecticides all together.


Assuntos
Peste , Sifonápteros , Xenopsylla , Yersinia pestis , Animais , Humanos , Insetos Vetores , Camundongos , Peste/epidemiologia , Peste/prevenção & controle , Peste/transmissão , Ratos
15.
PLoS Negl Trop Dis ; 14(9): e0008688, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32946437

RESUMO

Yersinia pestis, the causative agent of plague, is a highly lethal pathogen transmitted by the bite of infected fleas. Once ingested by a flea, Y. pestis establish a replicative niche in the gut and produce a biofilm that promotes foregut colonization and transmission. The rat flea Xenopsylla cheopis is an important vector to several zoonotic bacterial pathogens including Y. pestis. Some fleas naturally clear themselves of infection; however, the physiological and immunological mechanisms by which this occurs are largely uncharacterized. To address this, RNA was extracted, sequenced, and distinct transcript profiles were assembled de novo from X. cheopis digestive tracts isolated from fleas that were either: 1) not fed for 5 days; 2) fed sterile blood; or 3) fed blood containing ~5x108 CFU/ml Y. pestis KIM6+. Analysis and comparison of the transcript profiles resulted in identification of 23 annotated (and 11 unknown or uncharacterized) digestive tract transcripts that comprise the early transcriptional response of the rat flea gut to infection with Y. pestis. The data indicate that production of antimicrobial peptides regulated by the immune-deficiency pathway (IMD) is the primary flea immune response to infection with Y. pestis. The remaining infection-responsive transcripts, not obviously associated with the immune response, were involved in at least one of 3 physiological themes: 1) alterations to chemosensation and gut peristalsis; 2) modification of digestion and metabolism; and 3) production of chitin-binding proteins (peritrophins). Despite producing several peritrophin transcripts shortly after feeding, including a subset that were infection-responsive, no thick peritrophic membrane was detectable by histochemistry or electron microscopy of rat flea guts for the first 24 hours following blood-feeding. Here we discuss the physiological implications of rat flea infection-responsive transcripts, the function of X. cheopis peritrophins, and the mechanisms by which Y. pestis may be cleared from the flea gut.


Assuntos
Trato Gastrointestinal/microbiologia , Transcriptoma , Xenopsylla/microbiologia , Yersinia pestis/genética , Yersinia pestis/metabolismo , Animais , Biofilmes , Epitélio/microbiologia , Epitélio/patologia , Feminino , Trato Gastrointestinal/patologia , Perfilação da Expressão Gênica , Insetos Vetores/microbiologia , Peste/microbiologia , Peste/veterinária , Ratos , Análise de Sequência de RNA , Yersinia pestis/crescimento & desenvolvimento , Yersinia pestis/isolamento & purificação
16.
Parasit Vectors ; 13(1): 335, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611387

RESUMO

BACKGROUND: Yersinia pestis is the flea-transmitted etiological agent of bubonic plague. Sylvatic plague consists of complex tripartite interactions between diverse flea and wild rodent species, and pathogen strains. Transmission by flea bite occurs primarily by the Y. pestis biofilm-mediated foregut blockage and regurgitation mechanism, which has been largely detailed by studies in the model interaction between Y. pestis KIM6+ and Xenopsylla cheopis. Here, we test if pathogen-specific traits influence this interaction by determining the dynamics of foregut blockage development in X. cheopis fleas among extant avirulent pCD1-Y. pestis strains, KIM6+ and CO92, belonging to distinct biovars, and a non-circulating mutant CO92 strain (CO92gly), restored for glycerol fermentation; a key biochemical difference between the two biovars. METHODS: Separate flea cohorts infected with distinct strains were evaluated for (i) blockage development, bacterial burdens and flea foregut blockage pathology, and (ii) for the number of bacteria transmitted by regurgitation during membrane feeding. Strain burdens per flea was determined for fleas co-infected with CO92 and KIM6+ strains at a ratio of 1:1. RESULTS: Strains KIM6+ and CO92 developed foregut blockage at similar rates and peak temporal incidences, but the CO92gly strain showed significantly greater blockage rates that peak earlier post-infection. The KIM6+ strain, however, exhibited a distinctive foregut pathology wherein bacterial colonization extended the length of the esophagus up to the feeding mouthparts in ~65% of blocked fleas; in contrast to 32% and 26%, respectively, in fleas blocked with CO92 and CO92gly. The proximity of KIM6+ to the flea mouthparts in blocked fleas did not result in higher regurgitative transmission efficiencies as all strains transmitted variable numbers of Y. pestis, albeit slightly lower for CO92gly. During competitive co-infection, strains KIM6+ and CO92 were equally fit maintaining equivalent infection proportions in fleas over time. CONCLUSIONS: We demonstrate that disparate foregut blockage pathologies exhibited by distinct extant Y. pestis strain genotypes do not influence transmission efficiency from X. cheopis fleas. In fact, distinct extant Y. pestis genotypes maintain equivalently effective blockage and transmission efficiencies which is likely advantageous to maintaining continued successful plague spread and establishment of new plague foci.


Assuntos
Sistema Digestório/patologia , Xenopsylla/microbiologia , Yersinia pestis , Animais , Biofilmes/crescimento & desenvolvimento , Sistema Digestório/microbiologia , Variação Genética , Insetos Vetores/microbiologia , Fenótipo , Peste/transmissão , Sifonápteros/microbiologia , Yersinia pestis/genética , Yersinia pestis/patogenicidade
17.
J Med Entomol ; 57(6): 1997-2007, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-32533162

RESUMO

Plague, caused by the flea-transmitted bacterial pathogen Yersinia pestis, is primarily a disease of wild rodents distributed in temperate and tropical zones worldwide. The ability of Y. pestis to develop a biofilm blockage that obstructs the flea foregut proventriculus facilitates its efficient transmission through regurgitation into the host bite site during flea blood sucking. While it is known that temperature influences transmission, it is not well-known if blockage dynamics are similarly in accord with temperature. Here, we determine the influence of the biologically relevant temperatures, 10 and 21°C, on blockage development in flea species, Xenopsylla cheopis (Rothschild) and Oropsylla montana (Baker), respectively, characterized by geographical distribution as cosmopolitan, tropical or endemic, temperate. We find that both species exhibit delayed development of blockage at 10°C. In Y. pestis infected X. cheopis, this is accompanied by significantly lower survival rates and slightly decreased blockage rates, even though these fleas maintain similar rates of persistent infection as at 21°C. Conversely, irrespective of infection status, O. montana withstand 21 and 10°C similarly well and show significant infection rate increases and slightly greater blocking rates at 10 versus 21°C, emphasizing that cooler temperatures are favorable for Y. pestis transmission from this species. These findings assert that temperature is a relevant parameter to consider in assessing flea transmission efficiency in distinct flea species residing in diverse geographical regions that host endemic plague foci. This is important to predict behavioral dynamics of plague regarding epizootic outbreaks and enzootic maintenance and improve timeous implementation of flea control programs.


Assuntos
Sifonápteros/microbiologia , Yersinia pestis/fisiologia , Animais , Feminino , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiologia , Masculino , Fatores Sexuais , Temperatura , Xenopsylla/microbiologia
18.
J Med Entomol ; 57(4): 1318-1323, 2020 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-32101616

RESUMO

The Oriental rat flea, Xenopsylla cheopis (Rothschild 1903), is a cosmopolitan flea usually found infesting domestic rats. This flea is a well-known major human plague vector in Madagascar. As part of field sampling, fleas and small mammals were collected in the village of South Andranofeno and the natural reserve of Sohisika, two sites of the district of Ankazobe, located in the Central Highlands of Madagascar. Rats inside houses and forest small mammals were trapped using Besancon Technical Services and pitfall traps, respectively. Their fleas were collected and preserved for laboratory works. Collected fleas from the village and forest belonged to five species, which were X. cheopis, Synopsyllus fonquerniei (Wagner and Roubaud 1932) (Siphonaptera: Pulicidae), Echidnophaga gallinacea (Westwood 1875) (Siphonaptera: Pulicidae), Ctenocephalides felisstrongylus (Jordan 1925) (Siphonaptera: Pulicidae), Pulex irritans (Linnaeus 1758) (Siphonaptera: Pulicidae). After sampling in the forest zone, one specimen of X. cheopis was unexpectedly collected while infesting an endemic tenrec Setifer setosus (Schreber 1777) (Afrosoricida: Tenrecidae). Polymerase chain reaction (PCR) diagnosis on all collected fleas allowed detecting plague bacterium Yersinia pestis (Lehmann and Neumann 1896) (Enterobacterales: Yersiniaceae) on nine specimens of the endemic flea S. fonquerniei collected inside forest. The presence of the oriental rat flea in forest highlights the connection between human and wild environments due to animal movements and the fact that the rat flea can infest various hosts. As only one specimen of X. cheopis was collected on S. setosus, we hypothesize that flea was carried from the village to forest. Yersinia pestis infection of forest fleas outlines plague circulation in this sylvatic area.


Assuntos
Distribuição Animal , Infestações por Pulgas/veterinária , Peste/transmissão , Xenopsylla/fisiologia , Yersinia pestis/isolamento & purificação , Animais , Infestações por Pulgas/parasitologia , Florestas , Madagáscar , Peste/microbiologia , Ratos , Xenopsylla/microbiologia
19.
Parasitology ; 147(6): 721-728, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32046805

RESUMO

To model the colonization of a novel host by fleas, Synosternus cleopatrae and Xenopsylla ramesis, we established experimental lines maintained for 15 generations on a principal or a novel host (either co-occurring with a flea or not). We compared the blood meal size and the energy expended for digestion by fleas from the 15th generation of each line on these hosts between hosts within a line and between lines within a host asking (a) whether fleas adapt to a novel host (increased blood consumption/decreased energy expended for digestion); (b) if yes, whether this adaptation leads to the loss of ability to exploit an original host, and (c) whether the success of adaptation to a novel host depends on its ecological co-occurrence with a flea. The blood consumption and digestion energetics of fleas fed on the principal host differed from those on other hosts. The effect of the principal host on feeding performance differed between fleas, with S. cleopatrae consuming less blood and expending more energy for digestion on the principal than on any other host, whereas the opposite was true for X. ramesis. No changes in feeding performance on a novel host over generations were found. We propose several explanations for the lack of adaptation to a novel host over time. We explain the poor performance of S. cleopatrae on its principal host via its immune response mounting pattern. We argue that the principal host of a parasite is not necessarily the host on which the parasite demonstrates the best performance.


Assuntos
Gerbillinae/parasitologia , Especificidade de Hospedeiro , Interações Hospedeiro-Parasita , Sifonápteros/fisiologia , Adaptação Biológica , Animais , Feminino , Masculino , Xenopsylla/fisiologia
20.
J Med Entomol ; 57(3): 893-900, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-31891169

RESUMO

Plague is a low incidence flea-borne zoonosis that is often fatal if treatment is delayed or inadequate. Outbreaks occur sporadically and human cases are often preceded by epizootics among rodents. Early recognition of epizootics coupled with appropriate prevention measures should reduce plague morbidity and mortality. For nearly a century, the flea index (a measure of fleas per host) has been used as a measure of risk for epizootic spread and human plague case occurrence, yet the practicality and effectiveness of its use in surveillance programs has not been evaluated rigorously. We sought to determine whether long-term monitoring of the Xenopsylla flea index on hut-dwelling rats in sentinel villages in the plague-endemic West Nile region of Uganda accurately predicted plague occurrence in the surrounding parish. Based on observations spanning ~6 yr, we showed that on average, the Xenopsylla flea index increased prior to the start of the annual plague season and tended to be higher in years when plague activity was reported in humans or rodents compared with years when it was not. However, this labor-intensive effort had limited spatial coverage and was a poor predictor of plague activity within sentinel parishes.


Assuntos
Epidemias , Peste/epidemiologia , Peste/veterinária , Ratos , Espécies Sentinelas , Vigilância de Evento Sentinela/veterinária , Xenopsylla/fisiologia , Animais , Densidade Demográfica , Estações do Ano , Uganda/epidemiologia
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