Biology subjects

Herren, J. K.

Publications and source records attributed to Herren, J. K..

6 recordsLinked to original sources

bioRxiv2026

Suppression of Plasmodium falciparum infection by Microsporidia MB in wild Anopheles arabiensis populations

Symbiont-based approaches offer a promising strategy for reducing malaria transmission by suppressing Plasmodium development in Anopheles mosquitoes. Microsporidia MB, a naturally occurring microsporidian symbiont of Anopheles arabiensis, inhibits Plasmodium falciparum development in the laboratory, but its efficacy under natural transmission conditions is unknown. Here we monitored Microsporidia MB in wild An. arabiensis over 30 months in western Kenya and identified distinct low- and high-intensity infection phenotypes consistent with horizontal and vertical transmission, respectively. Overall, Microsporidia MB was associated with approximately 50% lower odds of P. falciparum infection. This association strengthened with symbiont intensity: high-intensity infections were associated with approximately 60% lower odds of Plasmodium infection compared with approximately 34% for low-intensity infections, identifying symbiont intensity as a key determinant of parasite-blocking efficacy. These findings provide evidence that Microsporidia MB suppresses P. falciparum infection in wild Anopheles populations, providing a key component of the field validation needed to advance Microsporidia MB as a candidate for malaria-control applications.

microbiology↗

bioRxiv2025

Changes in the Anopheles arabiensis transcriptome and gut microbiota profiles associated with Microsporidia MB

Microsporidia MB is an endosymbiotic microbe found in Anopheles mosquito populations. This symbiont can block Plasmodium transmission in mosquitoes, and it can spread through mosquito populations and be sustained over generations by vertical and horizontal transmission. These characteristics make Microsporidia MB a potential candidate for symbiont-based malaria vector control. However, the mechanistic basis of interactions between Microsporidia MB and Anopheles arabiensis is poorly characterized. We investigated how the presence of Microsporidia MB affects transcriptomics profiles and the gut microbiota composition and diversity in non-blood-fed and blood-fed (24, 48 and 72 hours post blood meal) An. arabiensis mosquitoes. We observed that mosquito infection with Microsporidia MB upregulated farnesoic acid O-methyltransferase, a gene linked to juvenile hormone biosynthesis in the non-blood-fed mosquitoes. In addition, blood feeding in Microsporidia MB positive mosquitoes was associated with an activation of immune-related genes 24 hours after a blood meal, where several genes including the lipopolysaccharide tumor necrosis factor gene were upregulated. Interestingly, we also observed that Microsporidia MB positivity was associated with a microbiota shift to favor the proliferation of microbes including Pseudomonas and Serratia 24 hours post blood meal. There were indications of immune system activation in Microsporidia MB positive mosquitoes up to 48 hours after a blood meal where factors such as the peptidoglycan recognition SC2-like and lysozyme c-1 were upregulated. Notably, an upregulated immune system at this time point was associated with downregulation of genes associated with metabolism and the restoration of Serratia, Pseudomonas and other key microbes to relative abundances similar to those recorded in non-blood-fed mosquitoes. At the 72-hour time point, Microsporidia MB positive mosquitoes exhibited a downregulation of genes associated with immunity, including cecropins and defensins, while metabolic processes were predominantly upregulated. Our results provide insights into the effect of Microsporidia MB infection on the An. arabiensis gene expression and gut microbiota profiles. This work will contribute to mechanistic insights into symbiont-mediated malaria transmission blocking.

systems biology↗

bioRxiv2024

Temperature modulates the dissemination potential of Microsporidia MB, a malaria-blocking endosymbiont of Anopheles mosquitoes

The endosymbiont Microsporidia MB is a promising malaria control strategy that inhibits the development of Plasmodium naturally in Anopheles mosquitoes. To be successful, it would be necessary to significantly increase the prevalence of Microsporidia MB in populations of malaria mosquitoes to decrease the malaria transmission potential of the mosquito population. However, very little is known about the role of temperature in driving the prevalence of Microsporidia MB infections in mosquito populations. By rearing mosquito larvae under four air temperature regimes (22{degrees}C, 27{degrees}C, 32{degrees}C and 37{degrees}C), we show that warm temperatures favour the growth of Microsporidia MB infected larvae. In addition, Microsporidia MB infected larvae developed faster compared to the uninfected offspring of the same mothers. Starting with 10 Microsporidia MB infected mothers, our population growth model showed that, at 32{degrees}C, it would take 15-35 days to reach a population of 1000 Microsporidia MB infected mothers; this represents a dissemination potential of 4.7, 1.3 and 1.7 times higher compared to 22{degrees}C, 27{degrees}C and 37{degrees}C, respectively. Despite a relatively high mosquito mortality rate (20% more compared to 27{degrees}C), 32{degrees}C was estimated the best temperature for rearing Microsporidia MB infected larvae due to the shorter development time and high infection rate. This study gives insight into the favourable conditions for Microsporidia MB mass rearing and potential release strategies in malarious regions. ImportanceMalaria parasites transmitted by Anopheles mosquitoes cause a life-threatening disease, imposing a massive toll on human health and economic sustainability in sub-Saharan Africa. Relying only on insecticide- and drug-based control products whose efficacy has been eroded by resistance to control malaria is not sufficient anymore. New innovative approaches are urgently needed and Microsporidia MB, a naturally occurring symbiont across Africa is capable of inhibiting Plasmodium transmission in Anopheles gambiae s.l.. Its success in adverting a rebound of malaria cases will depend on the infection dynamic of the symbiont over time and space. Through experimental studies on field derived mosquitoes and mathematical modelling, we demonstrate that Microsporidia MB dissemination potential increase with temperature within a viable range for Anopheles mosquitoes, due to trade-offs between mosquito development and survival and the symbiont growth. Future studies should now investigate how fluctuating temperatures modulate the Plasmodium transmission blocking performance in nature.

microbiology↗

bioRxiv2024

The Plasmodium transmission-blocking symbiont, Microsporidia MB, is vertically transmitted through Anopheles arabiensis germline stem cells

Microsporidia MB is a promising candidate for developing a symbiont-based strategy for malaria control because it disrupts the capacity of An. arabiensis to transmit the Plasmodium parasite. The symbiont is predominantly localized in the reproductive organs and is transmitted vertically from mother to offspring and horizontally (sexually) during mating. Due to the contribution of both transmission routes, Microsporidia MB has the potential to spread through target vector populations and become established at high prevalence. Stable and efficient vertical transmission of Microsporidia MB is important for its sustainable use for malaria control, however, the vertical transmission efficiency of Microsporidia MB can vary. In this study, we investigate the mechanistic basis of Microsporidia MB vertical transmission in An. arabiensis. We show that vertical transmission occurs through the acquisition of Microsporidia MB by Anopheles cystocyte progenitors following the division of germline stem cells. We also show that Microsporidia MB replicates to increase infection intensity in the oocyte of developing eggs when mosquitoes are given a blood meal suggesting that symbiont proliferation in the ovary is coordinated with egg development. The rate of Microsporidia MB transmission to developing eggs is on average higher than the recorded (mother to adult offspring) vertical transmission rate. This likely indicates that a significant proportion of An. arabiensis offspring lose their Microsporidia MB symbionts during development. The stability of germline stem cell infections, coordination of symbiont proliferation, and very high rate of transmission from germline stem cells to developing eggs indicate that Microsporidia MB has a highly specialized vertical transmission strategy in An. arabiensis, which may explain host specificity. Author SummaryMosquito vectors of diseases are associated with a broad range of microbes. Some of the microbes significantly affect vector biology including pathogen transmission efficiency. Anopheles mosquitoes, which transmit the malaria parasite, Plasmodium falciparum, harbor a native microbe known as Microsporidia MB. This microbe interferes with the formation of transmissible stages of the parasite that are transferred to humans by female mosquitoes when taking a blood meal. This phenotype can be exploited to develop a novel strategy for controlling malaria similar to the control of dengue fever using Aedes mosquitoes carrying Wolbachia bacteria. Mother-to-offspring transmission of protective microbes is important in sustainable application of microbe-based technologies to control vector-borne diseases because it ensures maintenance of the microbe in target vector populations across many generations. Here, we investigated stability of Microsporidia MB infections and efficiency of mother-to-offspring transmission during early stages of egg formation and development. We found that this microbe has a specialized transmission mechanism that involves infecting the germline cells that are important in egg production. We also demonstrated a very high transmission rate (97%) of the Microsporidia MB from infected germline cells into daughter cells during cell division. As the germline daughter cells developed into eggs, Microsporidia MB established itself in the egg yolk through active replication which only occured after the female mosquitoes had a blood meal. Our study gives insights into an efficient mother-to-offspring transmission route of Microsporidia MB that can be utilized sustainably in microbe-based intervention to control malaria.

ecology↗

bioRxiv2023

Localisation and tissue tropism of the symbiont Microsporidia MB in the germ line and somatic tissues of Anopheles arabiensis

The Anopheles symbiont, Microsporidia MB, is maternally inherited and has a strong malaria transmission-blocking phenotype in Anopheles arabiensis. Microsporidia MB is also vertically transmitted, sexually transmitted and avirulent. These characteristics are expected to promote its spread through mosquito populations, enhancing the potential of Microsporidia MB as a candidate for the development of a symbiont-mediated malaria transmission blocking strategy. We found that the patterns of Microsporidia MB localisation over the development of An. arabiensis indicate accumulation in tissues linked to its transmission, specifically the male and female gonadal tissues. Transovarial vertical transmission of Microsporidia MB occurs in the female An. arabiensis ovary when Microsporidia MB becomes localised to the cytoplasm of the developing oocyte. In male An. arabiensis, Microsporidia MB is localised in the testis and vas deferens. Notably, a high intensity of Microsporidia MB can also be observed in the An. arabiensis adult but not larval gut. The levels of Microsporidia MB found in the female ovary are linked to the progression of oogenesis, increasing after blood feeding initiates the development of eggs. The levels of Microsporiodia MB in the male and female gonadal and gut tissue do not increase as mosquitoes age. Altogether, the high specificity of Microsporidia MB tissue localisation patterns and changes in infection prevalence and intensity suggest adaptation to maximise transmission and avirulence in Anopheles arabiensis. ImportanceMicrosporidia MB is a symbiont with strong malaria transmission-blocking phenotype in Anopheles arabiensis. It spreads in mosquito populations through mother-to-offspring and sexual transmission. The ability of Microsporidia MB to block Plasmodium transmission together with its ability to spread within Anopheles populations and its avirulence to the host makes it a very attractive candidate for developing a key strategy to stop malaria transmissions. Here, we report the basis of Microsporidia MB transmission. We find that Microsporidia MB accumulates in Anopheles arabiensis tissues linked to its sexual and vertical transmission. Its prevalence and intensity in the tissues over the mosquito life cycle suggest adaptation to maximise transmission and avirulence in Anopheles arabiensis. These findings provide the foundation for understanding the factors that affect Microsporidia MB transmission efficiency. This will contribute to the establishment of strategies to maximize Microsporidia MB transmission for Anopheles mosquito population replacement and malaria transmission blocking.

microbiology↗

bioRxiv2019

A Microsporidian blocks Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

Malaria imposes an enormous burden on sub-Saharan Africa, and evidence that incidence could be starting to increase again1 suggests the limits of currently applied control strategies have now been reached. A possible novel control approach involves the dissemination in mosquitoes of inherited symbiotic microbes to block transmission. This strategy is exemplified by the use of transmission-blocking Wolbachia in Aedes aegypti against dengue virus2-7. However, in the Anopheles gambiae complex, the primary African vectors of malaria, there limited reports of inherited symbionts with transmission-blocking capacity8-10. Here we show that a newly discovered vertically transmitted species of Microsporidia symbiont in the An. gambiae complex blocks Plasmodium transmission. Microsporidia MB is present at moderate prevalence in geographically dispersed populations of An. arabienesis in Kenya, localized to the mosquito midgut and ovaries, and is not associated with significant reductions in adult host fecundity or survival. Field collected Microsporidia MB-infected An. arabiensis were never found to harbor P. falciparum gametocytes and on experimental infection with P. falciparum no sporozoites could be detected in Microsporidia MB-infected mosquitos. As a Plasmodium transmission-blocking microbe that is non-virulent and vertically transmitted, Microsporidia MB could be exploited as a novel malaria control tool.

microbiology↗