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1.
J Theor Biol ; 542: 111110, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35364056

RESUMO

Releasing mosquitoes transinfected with the endosymbiotic bacterium Wolbachia is a novel strategy for interrupting vector-borne pathogen transmission. Following its success in controlling arboviruses spread by Aedes aegypti, this technology is being adapted for anopheline malaria vectors. However, antagonistic interactions between Wolbachia and naturally resident Asaia bacteria in malaria vectors have been demonstrated experimentally, potentially jeopardising Wolbachia biocontrol. We developed the first mathematical model accounting for interspecific competition between endosymbionts to assess the feasibility of this novel strategy for controlling malaria. First, Asaia prevalences among natural mosquito populations were compared with simulations parametrized with rates of Asaia transmission reported from laboratory studies. Discrepancies between projections and natural Asaia prevalences indicated potential overestimation of Asaia transmissibility in artificial laboratory settings. With parametrization that matches natural Asaia prevalence, simulations identified redundancies in Asaia's many infection routes (vertical, sexual and environmental). This resilience was only overcome when Wolbachia conferred very high resistance to environmental infection with Asaia, resulting in Wolbachia fixation and Asaia exclusion. Wolbachia's simulated spread was prevented when its maternal transmission was impeded in coinfected mosquitoes and the pre-control Asaia prevalence was beyond a threshold of 60-75%. This theoretical assessment highlights critical next steps in laboratory experiments to inform this strategy's feasibility.


Assuntos
Aedes , Anopheles , Malária , Wolbachia , Animais , Estudos de Viabilidade , Modelos Teóricos , Mosquitos Vetores
2.
Viruses ; 14(4)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35458433

RESUMO

Dengue is an arboviral disease caused by dengue virus (DENV), leading to approximately 25,000 deaths/year and with over 40% of the world's population at risk. Increased international travel and trade, poorly regulated urban expansion, and warming global temperatures have expanded the geographic range and incidence of the virus in recent decades. This study used phylogenetic and selection pressure analyses to investigate trends in DENV evolution, using whole genome coding sequences from publicly available databases alongside newly sequenced isolates collected between 1963-1997 from Southeast Asia and the Pacific. Results revealed very similar phylogenetic relationships when using the envelope gene and the whole genome coding sequences. Although DENV evolution is predominantly driven by negative selection, a number of amino acid sites undergoing positive selection were found across the genome, with the majority located in the envelope and NS5 genes. Some genotypes appear to be diversifying faster than others within each serotype. The results from this research improve our understanding of DENV evolution, with implications for disease control efforts such as Wolbachia-based biocontrol and vaccine design.


Assuntos
Vírus da Dengue , Dengue , Wolbachia , Evolução Molecular , Genoma Viral , Genótipo , Humanos , Filogenia
3.
PLoS Negl Trop Dis ; 16(4): e0010284, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35442957

RESUMO

The Applying Wolbachia to Eliminate Dengue (AWED) trial was a parallel cluster randomised trial that demonstrated Wolbachia (wMel) introgression into Ae. aegypti populations reduced dengue incidence. In this predefined substudy, we compared between treatment arms, the relative abundance of Ae. aegypti and Ae. albopictus before, during and after wMel-introgression. Between March 2015 and March 2020, 60,084 BG trap collections yielded 478,254 Ae. aegypti and 17,623 Ae. albopictus. Between treatment arms there was no measurable difference in Ae. aegypti relative abundance before or after wMel-deployments, with a count ratio of 0.96 (95% CI 0.76, 1.21) and 1.00 (95% CI 0.85, 1.17) respectively. More Ae. aegypti were caught per trap per week in the wMel-intervention arm compared to the control arm during wMel deployments (count ratio 1.23 (95% CI 1.03, 1.46)). Between treatment arms there was no measurable difference in the Ae. albopictus population size before, during or after wMel-deployment (overall count ratio 1.10 (95% CI 0.89, 1.35)). We also compared insecticide resistance phenotypes of Ae. aegypti in the first and second years after wMel-deployments. Ae. aegypti field populations from wMel-treated and untreated arms were similarly resistant to malathion (0.8%), permethrin (1.25%) and cyfluthrin (0.15%) in year 1 and year 2 of the trial. In summary, we found no between-arm differences in the relative abundance of Ae. aegypti or Ae. albopictus prior to or after wMel introgression, and no between-arm difference in Ae. aegypti insecticide resistance phenotypes. These data suggest neither Aedes abundance, nor insecticide resistance, confounded the epidemiological outcomes of the AWED trial.


Assuntos
Aedes , Vírus da Dengue , Dengue , Wolbachia , Animais , Dengue/epidemiologia , Dengue/prevenção & controle , Resistência a Inseticidas , Mosquitos Vetores
4.
Proc Natl Acad Sci U S A ; 119(15): e2120003119, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35377795

RESUMO

Significance Lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori affects 51 million people, leading to severe physical and mental disabilities. A mutualistic symbiosis between these filarial nematodes and Wolbachia bacteria has been exploited as a new curative treatment. Epidemiological modeling of anti-Wolbachia treatment assumes that transmission persists due to the lag phase before microfilariae (mf) become removed from circulation. Here, we show that Wolbachia-depleted mf cannot develop within the mosquito vector-a phenotype associated with down-regulation of B. malayi mf-specific chitinase, an enzyme essential for exsheathment. Our findings add to the broad range of host biological processes dependent on Wolbachia and suggest that anti-Wolbachia treatment mediates a more accelerated impact on elimination of lymphatic filariasis than currently predicted.


Assuntos
Antibacterianos , Quitinases , Filariose Linfática , Microfilárias , Wolbachia , Animais , Antibacterianos/farmacologia , Quitinases/genética , Filariose Linfática/transmissão , Humanos , Microfilárias/enzimologia , Microfilárias/crescimento & desenvolvimento , Microfilárias/microbiologia , Mosquitos Vetores/parasitologia , Wolbachia/efeitos dos fármacos , Wolbachia/genética
5.
Proc Biol Sci ; 289(1972): 20212781, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35414231

RESUMO

Arthropods host a range of sex-ratio-distorting selfish elements, including diverse maternally inherited endosymbionts that solely kill infected males. Male-killing heritable microbes are common, reach high frequency, but until recently have been poorly understood in terms of the host-microbe interaction. Additionally, while male killing should generate strong selection for host resistance, evidence of this has been scant. The interface of the microbe with host sex determination is integral to the understanding of how death is sex limited and how hosts can evolve evasion of male killing. We first review current knowledge of the mechanisms diverse endosymbionts use to induce male-specific death. We then examine recent evidence that these agents do produce intense selection for host nuclear suppressor elements. We argue, from our understanding of male-killing mechanisms, that suppression will commonly involve evolution of the host sex determination pathways and that the host's response to male-killing microbes thus represents an unrecognized driver of the diversity of arthropod sex determination. Further work is required to identify the genes and mechanisms responsible for male-killing suppression, which will both determine the components of sex determination (or other) systems associated with suppressor evolution, and allow insight into the mechanism of male killing itself.


Assuntos
Artrópodes , Wolbachia , Animais , Artrópodes/microbiologia , Bactérias/genética , Masculino , Razão de Masculinidade , Simbiose , Wolbachia/fisiologia
6.
Curr Microbiol ; 79(6): 173, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35488963

RESUMO

Wolbachia infections affect the reproductive system and various biological traits of the host insect. There is a high frequency of Wolbachia infection in the leafhopper Yamatotettix flavovittatus Matsumura. To investigate the potential roles of Wolbachia in the host, it is important to generate a non-Wolbachia-infected line. The efficacy of antibiotics in eliminating Wolbachia from Y. flavovittatus remains unknown. This leafhopper harbors the mutualistic bacterium Candidatus Sulcia muelleri, which has an important function in the biological traits. The presence of Ca. S. muelleri raises a major concern regarding the use of antibiotics. We selectively eliminated Wolbachia, considering the influence of antibiotics on leafhopper survival and Ca. S. muelleri prevalence. The effect of artificial diets containing different doses of tetracycline and rifampicin on survival was optimized; high dose (0.5 mg/ml) of antibiotics induces a high mortality. A concentration of 0.2 mg/ml was chosen for the subsequent experiments. Antibiotic treatments significantly reduced the Wolbachia infection, and the Wolbachia density in the treated leafhoppers sharply declined. Wolbachia recurred in tetracycline-treated offspring, regardless of antibiotic exposure. However, Wolbachia is unable to be transmitted and restored in rifampicin-treated offspring. The dose and treatment duration had no significant effect on the infection and density of Ca. S. muelleri in the antibiotic-treated offspring. In conclusion, Wolbachia in Y. flavovittatus was stably eliminated using rifampicin, and the Wolbachia-free line was generated at least two generations after treatment. This report provides additional experimental procedures for removing Wolbachia from insects, particularly in host species with the coexistence of Ca. S. muelleri.


Assuntos
Hemípteros , Wolbachia , Animais , Antibacterianos/farmacologia , Hemípteros/microbiologia , Rifampina/farmacologia , Tetraciclina/farmacologia
7.
Chaos ; 32(4): 041105, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35489839

RESUMO

Over the last decade, the release of Wolbachia-infected Aedes aegypti into the natural habitat of this mosquito species has become the most sustainable and long-lasting technique to prevent and control vector-borne diseases, such as dengue, zika, or chikungunya. However, the limited resources to generate such mosquitoes and their effective distribution in large areas dominated by the Aedes aegypti vector represent a challenge for policymakers. Here, we introduce a mathematical framework for the spread of dengue in which competition between wild and Wolbachia-infected mosquitoes, the cross-contagion patterns between humans and vectors, the heterogeneous distribution of the human population in different areas, and the mobility flows between them are combined. Our framework allows us to identify the most effective areas for the release of Wolbachia-infected mosquitoes to achieve a large decrease in the global dengue prevalence.


Assuntos
Aedes/microbiologia , Febre de Chikungunya/prevenção & controle , Dengue/prevenção & controle , Mosquitos Vetores/microbiologia , Wolbachia/fisiologia , Infecção por Zika virus/prevenção & controle , Animais , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/transmissão , Dengue/epidemiologia , Dengue/transmissão , Humanos , Controle de Mosquitos/economia , Wolbachia/crescimento & desenvolvimento , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissão
9.
Parasit Vectors ; 15(1): 128, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413938

RESUMO

BACKGROUND: The insect endosymbiotic bacterium Wolbachia is being deployed in field populations of the mosquito Aedes aegypti for biological control. This microbe prevents the replication of human disease-causing viruses inside the vector, including dengue, Zika and chikungunya. Relative Wolbachia densities may in part predict the strength of this 'viral blocking' effect. Additionally, Wolbachia densities may affect the strength of the reproductive manipulations it induces, including cytoplasmic incompatibility (CI), maternal inheritance rates or induced fitness effects in the insect host. High rates of CI and maternal inheritance and low rates of fitness effects are also key to the successful spreading of Wolbachia through vector populations and its successful use in biocontrol. The factors that control Wolbachia densities are not completely understood. METHODS: We used quantitative PCR-based methods to estimate relative density of the Wolbachia wAlbB strain in both the somatic and reproductive tissues of adult male and female mosquitoes, as well as in eggs. Using correlation analyses, we assessed whether densities in one tissue predict those in others within the same individual, but also across generations. RESULTS: We found little relationship among the relative Wolbachia densities of different tissues in the same host. The results also show that there was very little relationship between Wolbachia densities in parents and those in offspring, both in the same and different tissues. The one exception was with ovary-egg relationships, where there was a strong positive association. Relative Wolbachia densities in reproductive tissues were always greater than those in the somatic tissues. Additionally, the densities were consistent in females over their lifetime regardless of tissue, whereas they were generally higher and more variable in males, particularly in the testes. CONCLUSIONS: Our results indicate that either stochastic processes or local tissue-based physiologies are more likely factors dictating Wolbachia densities in Ae. aegypti individuals, rather than shared embryonic environments or heritable genetic effects of the mosquito genome. These findings have implications for understanding how relative Wolbachia densities may evolve and/or be maintained over the long term in Ae. aegypti.


Assuntos
Aedes , Wolbachia , Infecção por Zika virus , Zika virus , Aedes/fisiologia , Animais , Feminino , Humanos , Masculino , Mosquitos Vetores/fisiologia , Gravidade Específica , Wolbachia/fisiologia
10.
PLoS Negl Trop Dis ; 16(4): e0010139, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35417447

RESUMO

The arbovirus vector Aedes albopictus (Asian tiger mosquito) is common throughout the Indo-Pacific region, where most global dengue transmission occurs. We analysed population genomic data and tested for cryptic species in 160 Ae. albopictus sampled from 16 locations across this region. We found no evidence of cryptic Ae. albopictus but found multiple intraspecific COI haplotypes partitioned into groups representing three Asian lineages: East Asia, Southeast Asia and Indonesia. Papua New Guinea (PNG), Vanuatu and Christmas Island shared recent coancestry, and Indonesia and Timor-Leste were likely invaded from East Asia. We used a machine learning trained on morphologically sexed samples to classify sexes using multiple genetic features and then characterized the wAlbA and wAlbB Wolbachia infections in 664 other samples. The wAlbA and wAlbB infections as detected by qPCR showed markedly different patterns in the sexes. For females, most populations had a very high double infection incidence, with 67% being the lowest value (from Timor-Leste). For males, the incidence of double infections ranged from 100% (PNG) to 0% (Vanuatu). Only 6 females were infected solely by the wAlbA infection, while rare uninfected mosquitoes were found in both sexes. The wAlbA and wAlbB densities varied significantly among populations. For mosquitoes from Torres Strait and Vietnam, the wAlbB density was similar in single-infected and superinfected (wAlbA and wAlbB) mosquitoes. There was a positive association between wAlbA and wAlbB infection densities in superinfected Ae. albopictus. Our findings provide no evidence of cryptic species of Ae. albopictus in the region and suggest site-specific factors influencing the incidence of Wolbachia infections and their densities. We also demonstrate the usefulness of ddRAD tag depths as sex-specific mosquito markers. The results provide baseline data for the exploitation of Wolbachia-induced cytoplasmic incompatibility (CI) in dengue control.


Assuntos
Aedes , Dengue , Wolbachia , Aedes/genética , Animais , DNA Mitocondrial/genética , Dengue/epidemiologia , Feminino , Masculino , Mosquitos Vetores/genética , Wolbachia/genética
11.
PLoS Negl Trop Dis ; 16(4): e0010324, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35471983

RESUMO

BACKGROUND: The combination of Wolbachia-based incompatible insect technique (IIT) and radiation-based sterile insect technique (SIT) can be used for population suppression of Aedes aegypti. Our main objective was to evaluate whether open-field mass-releases of wAlbB-infected Ae. aegypti males, as part of an Integrated Vector Management (IVM) plan led by the Mexican Ministry of Health, could suppress natural populations of Ae. aegypti in urbanized settings in south Mexico. METHODOLOGY/PRINCIPAL FINDINGS: We implemented a controlled before-and-after quasi-experimental study in two suburban localities of Yucatan (Mexico): San Pedro Chimay (SPC), which received IIT-SIT, and San Antonio Tahdzibichén used as control. Release of wAlbB Ae. aegypti males at SPC extended for 6 months (July-December 2019), covering the period of higher Ae. aegypti abundance. Entomological indicators included egg hatching rates and outdoor/indoor adult females collected at the release and control sites. Approximately 1,270,000 lab-produced wAlbB-infected Ae. aegypti males were released in the 50-ha treatment area (2,000 wAlbB Ae. aegypti males per hectare twice a week in two different release days, totaling 200,000 male mosquitoes per week). The efficacy of IIT-SIT in suppressing indoor female Ae. aegypti density (quantified from a generalized linear mixed model showing a statistically significant reduction in treatment versus control areas) was 90.9% a month after initiation of the suppression phase, 47.7% two months after (when number of released males was reduced in 50% to match local abundance), 61.4% four months after (when initial number of released males was re-established), 88.4% five months after and 89.4% at six months after the initiation of the suppression phase. A proportional, but lower, reduction in outdoor female Ae. aegypti was also quantified (range, 50.0-75.2% suppression). CONCLUSIONS/SIGNIFICANCE: Our study, the first open-field pilot implementation of Wolbachia IIT-SIT in Mexico and Latin-America, confirms that inundative male releases can significantly reduce natural populations of Ae. aegypti. More importantly, we present successful pilot results of the integration of Wolbachia IIT-SIT within a IVM plan implemented by Ministry of Health personnel.


Assuntos
Aedes , Infertilidade Masculina , Wolbachia , Animais , Feminino , Humanos , Insetos , Masculino , México , Controle de Mosquitos/métodos , Mosquitos Vetores , Projetos Piloto
12.
PLoS Pathog ; 18(3): e1010393, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35294495

RESUMO

Arthropod endosymbiont Wolbachia pipientis is part of a global biocontrol strategy to reduce the replication of mosquito-borne RNA viruses such as alphaviruses. We previously demonstrated the importance of a host cytosine methyltransferase, DNMT2, in Drosophila and viral RNA as a cellular target during pathogen-blocking. Here we report a role for DNMT2 in Wolbachia-induced alphavirus inhibition in Aedes species. Expression of DNMT2 in mosquito tissues, including the salivary glands, is elevated upon virus infection. Notably, this is suppressed in Wolbachia-colonized animals, coincident with reduced virus replication and decreased infectivity of progeny virus. Ectopic expression of DNMT2 in cultured Aedes cells is proviral, increasing progeny virus infectivity, and this effect of DNMT2 on virus replication and infectivity is dependent on its methyltransferase activity. Finally, examining the effects of Wolbachia on modifications of viral RNA by LC-MS show a decrease in the amount of 5-methylcytosine modification consistent with the down-regulation of DNMT2 in Wolbachia colonized mosquito cells and animals. Collectively, our findings support the conclusion that disruption of 5-methylcytosine modification of viral RNA is a vital mechanism operative in pathogen blocking. These data also emphasize the essential role of epitranscriptomic modifications in regulating fundamental alphavirus replication and transmission processes.


Assuntos
Aedes , Alphavirus , Artrópodes , Flavivirus , Wolbachia , 5-Metilcitosina/metabolismo , Alphavirus/genética , Animais , Artrópodes/genética , Flavivirus/genética , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Replicação Viral , Wolbachia/fisiologia
13.
Proc Biol Sci ; 289(1971): 20212582, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35350856

RESUMO

It is hard to overemphasize the importance of endosymbionts in arthropod biology, ecology and evolution. Some endosymbionts can complement host metabolic function or provide defence against pathogens; others, such as ubiquitous Wolbachia and Cardinium, have evolved strategies to manipulate host reproduction. A common reproductive manipulation strategy is cytoplasmic incompatibility (CI) between differently infected individuals which can result in female mortality or male development of fertilized eggs in haplodiploid hosts. Recently, an additional role of endosymbionts has been recognized in the modification of sex allocation in sexually reproducing haplodiploids. This was theoretically expected due to the maternal inheritance of endosymbionts and natural selection for them to increase infected female production, yet the underlying mechanism remained unknown. Here, we tested whether and how Cardinium and Wolbachia causing different CI types interact to increase female production in a haplodiploid thrips species where sex allocation depends on both maternal condition and egg size provisioning. We found that Cardinium augmented female production by increasing maternal fitness and egg size, thereby boosting fertilization rate and offspring fitness. Wolbachia, in contrast, reduced the beneficial effects of Cardinium. Our results demonstrate different invasion strategies and antagonistic effects of endosymbiotic bacteria on host fitness and evolution of sex allocation.


Assuntos
Artrópodes , Wolbachia , Animais , Bacteroidetes , Feminino , Humanos , Masculino , Reprodução , Simbiose
14.
Environ Microbiol ; 24(3): 1638-1652, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35229443

RESUMO

Microbiome analysis in a host-parasitoid interaction network was conducted to compare the taxonomic composition of bacterial communities of Diaphornia citri, Tamarixia radiata, and Diaphorencyrtus aligarhensis. The comparative analysis revealed differences in the composition and diversity of the symbiont populations across the host and its associated parasitoids. Proteobacteria was the most dominant phylum, representing 67.80% of the total bacterial community, while Candidatus Profftella armature and Wolbachia were the dominant genera across the host and parasitoids. There were clear differences observed in alpha and beta diversity of microbiota through the host and its associated parasitoids. The function prediction of bacterial communities and Pearson correlation analysis showed that specific bacterial communities displayed positive correlations with the carbohydrate metabolism pathway. Furthermore, when symbiotic bacteria were eliminated using a broad-spectrum antibiotic, tetracycline hydrochloride, the parasitoids' median survival time and longevity were significantly reduced. We confirmed the physiological effects of symbiotic bacteria on the fitness of parasitoids and demonstrated the effect of antibiotics in decreasing the food intake and measurement of amino acids in the hemolymph. This study sheds light on basic information about the mutualism between parasitoids and bacteria, which may be a potential source for biocontrol strategies for citrus psyllid, especially D. citri.


Assuntos
Citrus , Hemípteros , Microbiota , Vespas , Wolbachia , Animais , Bactérias , Citrus/microbiologia , Hemípteros/microbiologia
15.
Sci Rep ; 12(1): 5175, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35338196

RESUMO

Several morphological and mitochondrial lineages of the alpine ringlet butterfly species Erebia pronoe have been described, indicating a complex phylogenetic structure. However, the existing data were insufficient and allow neither a reconstruction of the biogeographic history, nor an assessment of the genetic lineages. Therefore, we analysed mitochondrial (COI, NDI) and nuclear (EF1α, RPS5) gene sequences and compared them with sequences from the sister species Erebia melas. Additionally, we combined this information with morphometric data of the male genitalia and the infection patterns with Wolbachia strains, based on a WSP analysis. We obtained a distinct phylogeographic structure within the E. pronoe-melas complex with eight well-distinguishable geographic groups, but also a remarkable mito-nuclear discordance. The mito-nuclear discordance in E. melas and E. pronoe glottis can be explained by different ages of Wolbachia infections with different Wolbachia strains, associated selective sweeps, and hybridisation inhibition. Additionally, we found indications for incipient speciation of E. pronoe glottis in the Pyrenees and a pronounced range dynamic within and among the other high mountain systems of Europe. Our results emphasize the importance of combined approaches in reconstructing biogeographic patterns and evaluating phylogeographic splits.


Assuntos
Borboletas , Síndrome MELAS , Wolbachia , Animais , Borboletas/genética , DNA Mitocondrial/genética , Variação Genética , Masculino , Filogenia , Wolbachia/genética
16.
Nat Commun ; 13(1): 1608, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35338130

RESUMO

Cytoplasmic incompatibility (CI) results when Wolbachia bacteria-infected male insects mate with uninfected females, leading to embryonic lethality. "Rescue" of viability occurs if the female harbors the same Wolbachia strain. CI is caused by linked pairs of Wolbachia genes called CI factors (CifA and CifB). The co-evolution of CifA-CifB pairs may account in part for the incompatibility patterns documented in insects infected with different Wolbachia strains, but the molecular mechanisms remain elusive. Here, we use X-ray crystallography and AlphaFold to analyze the CI factors from Wolbachia strain wMel called CidAwMel and CidBwMel. Substituting CidAwMel interface residues with those from CidAwPip (from strain wPip) enables the mutant protein to bind CidBwPip and rescue CidBwPip-induced yeast growth defects, supporting the importance of CifA-CifB interaction in CI rescue. Sequence divergence in CidAwPip and CidBwPip proteins affects their pairwise interactions, which may help explain the complex incompatibility patterns of mosquitoes infected with different wPip strains.


Assuntos
Wolbachia , Animais , Citoplasma/genética , Citosol , Drosophila melanogaster/genética , Feminino , Masculino , Saccharomyces cerevisiae , Simbiose/genética , Wolbachia/genética , Wolbachia/metabolismo
17.
Environ Microbiol ; 24(4): 2119-2135, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35319146

RESUMO

Mosquito-borne diseases remain a major cause of morbidity and mortality. Population replacement strategies involving the wMel strain of Wolbachia are being used widely to control mosquito-borne diseases. However, these strategies may be influenced by temperature because wMel is vulnerable to heat. wMel infections in Drosophila melanogaster are genetically diverse, but few transinfections of wMel variants have been generated in Aedes aegypti. Here, we successfully transferred a wMel variant (termed wMelM) originating from a field-collected D. melanogaster into Ae. aegypti. The new wMelM variant (clade I) is genetically distinct from the original wMel transinfection (clade III), and there are no genomic differences between wMelM in its original and transinfected host. We compared wMelM with wMel in its effects on host fitness, temperature tolerance, Wolbachia density, vector competence, cytoplasmic incompatibility and maternal transmission under heat stress in a controlled background. wMelM showed a higher heat tolerance than wMel, likely due to higher overall densities within the mosquito. Both wMel variants had minimal host fitness costs, complete cytoplasmic incompatibility and maternal transmission, and dengue virus blocking under laboratory conditions. Our results highlight phenotypic differences between Wolbachia variants and wMelM shows potential as an alternative strain in areas with strong seasonal temperature fluctuations.


Assuntos
Aedes , Wolbachia , Aedes/genética , Animais , Drosophila melanogaster/genética , Resposta ao Choque Térmico , Mosquitos Vetores , Wolbachia/genética
18.
mBio ; 13(2): e0386321, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35357208

RESUMO

Wolbachia are maternally transmitted intracellular bacteria that are not only restricted to the reproductive organs but also found in various somatic tissues of their native hosts. The abundance of the endosymbiont in the soma, usually a dead end for vertically transmitted bacteria, causes a multitude of effects on life history traits of their hosts, which are still not well understood. Thus, deciphering the host-symbiont interactions on a cellular level throughout a host's life cycle is of great importance to understand their homeostatic nature, persistence, and spreading success. Using fluorescent and transmission electron microscopy, we conducted a comprehensive analysis of Wolbachia tropism in soma and germ line of six Drosophila species at the intracellular level during host development. Our data uncovered diagnostic patterns of infections to embryonic primordial germ cells and to particular cells of the soma in three different neotropical Drosophila species that have apparently evolved independently. We further found that restricted patterns of Wolbachia tropism are determined in early embryogenesis via selective autophagy, and their spatially restricted infection patterns are preserved in adult flies. We observed tight interactions of Wolbachia with membranes of the endoplasmic reticulum, which might play a scaffolding role for autophagosome formation and subsequent elimination of the endosymbiont. Finally, by analyzing D. simulans lines transinfected with nonnative Wolbachia, we uncovered that the host genetic background regulates tissue tropism of infection. Our data demonstrate a novel and peculiar mechanism to limit and spatially restrict bacterial infection in the soma during a very early stage of host development. IMPORTANCE All organisms are living in close and intimate interactions with microbes that cause conflicts but also cooperation between both unequal genetic partners due to their different innate interests of primarily enhancing their own fitness. However, stable symbioses often result in homeostatic interaction, named mutualism, by balancing costs and benefits, where both partners profit. Mechanisms that have evolved to balance and stably maintain homeostasis in mutualistic relationships are still quite understudied; one strategy is to "domesticate" potentially beneficial symbionts by actively controlling their replication rate below a critical and, hence, costly threshold, and/or to spatially and temporally restrict their localization in the host organism, which, in the latter case, in its most extreme form, is the formation of a specialized housing organ for the microbe (bacteriome). However, questions remain: how do these mutualistic associations become established in their first place, and what are the mechanisms for symbiont control and restriction in their early stages? Here, we have uncovered an unprecedented symbiont control mechanism in neotropical Drosophila species during early embryogenesis. The fruit fly evolved selective autophagy to restrict and control the proliferation of its intracellular endosymbiont Wolbachia in a defined subset of the stem cells as soon as the host's zygotic genome is activated.


Assuntos
Wolbachia , Animais , Autofagia , Drosophila/microbiologia , Desenvolvimento Embrionário , Retículo Endoplasmático , Wolbachia/genética
19.
Trials ; 23(1): 185, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35236394

RESUMO

BACKGROUND: Arboviruses transmitted by Aedes aegypti including dengue, Zika, and chikungunya are a major global health problem, with over 2.5 billion at risk for dengue alone. There are no licensed antivirals for these infections, and safe and effective vaccines are not yet widely available. Thus, prevention of arbovirus transmission by vector modification is a novel approach being pursued by multiple researchers. However, the field needs high-quality evidence derived from randomized, controlled trials upon which to base the implementation and maintenance of vector control programs. Here, we report the EVITA Dengue trial design (DMID 17-0111), which assesses the efficacy in decreasing arbovirus transmission of an innovative approach developed by the World Mosquito Program for vector modification of Aedes mosquitoes by Wolbachia pipientis. METHODS: DMID 17-0111 is a cluster-randomized trial in Belo Horizonte, Brazil, with clusters defined by primary school catchment areas. Clusters (n = 58) will be randomized 1:1 to intervention (release of Wolbachia-infected Aedes aegypti mosquitoes) vs. control (no release). Standard vector control activities (i.e., insecticides and education campaigns for reduction of mosquito breeding sites) will continue as per current practice in the municipality. Participants (n = 3480, 60 per cluster) are children aged 6-11 years enrolled in the cluster-defining school and living within the cluster boundaries who will undergo annual serologic surveillance for arboviral infection. The primary objective is to compare sero-incidence of arboviral infection between arms. DISCUSSION: DMID 17-0111 aims to determine the efficacy of Wolbachia-infected mosquito releases in reducing human infections by arboviruses transmitted by Aedes aegypti and will complement the mounting evidence for this method from large-scale field releases and ongoing trials. The trial also represents a critical step towards robustness and rigor for how vector control methods are assessed, including the simultaneous measurement and correlation of entomologic and epidemiologic outcomes. Data from this trial will inform further the development of novel vector control methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT04514107 . Registered on 17 August 2020 Primary sponsor: National Institute of Health, National Institute of Allergy and Infectious Diseases.


Assuntos
Aedes , Vírus da Dengue , Dengue , Wolbachia , Infecção por Zika virus , Zika virus , Animais , Brasil/epidemiologia , Criança , Dengue/epidemiologia , Dengue/prevenção & controle , Humanos , Incidência , Mosquitos Vetores , Infecção por Zika virus/epidemiologia
20.
Curr Biol ; 32(6): R287-R289, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35349818

RESUMO

The Wolbachia cidA and cidB genes promote bacterial endosymbiont inheritance through the host female germline. CidB is now shown to load into maturing sperm nuclei. Following fertilization, it disrupts paternal chromosome condensation, triggering embryonic arrest if not countered by CidA in Wolbachia-infected eggs.


Assuntos
Wolbachia , Animais , Antídotos , Citoplasma , Citosol , Drosophila melanogaster/genética , Wolbachia/genética
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