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Table of Contents
Year : 2020  |  Volume : 10  |  Issue : 8  |  Page : 341-342

Vector-borne diseases: Mosquito holobiont and novel methods for vector control

1 Department of Earth and Environmental Sciences, School of Natural Sciences, University of Manchester, England, United Kingdom; Division of Vector-Borne Diseases, ICMR - National Institute of Research in Tribal Health, Jabalpur - 482003, India
2 Division of Vector-Borne Diseases, ICMR - National Institute of Research in Tribal Health, Jabalpur - 482003, India

Date of Submission27-May-2020
Date of Decision03-Jun-2020
Date of Acceptance04-Jun-2020
Date of Web Publication29-Jun-2020

Correspondence Address:
Aparup Das
Division of Vector-Borne Diseases, ICMR - National Institute of Research in Tribal Health, Jabalpur - 482003
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2221-1691.287160

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How to cite this article:
Singh US, Das A. Vector-borne diseases: Mosquito holobiont and novel methods for vector control. Asian Pac J Trop Biomed 2020;10:341-2

How to cite this URL:
Singh US, Das A. Vector-borne diseases: Mosquito holobiont and novel methods for vector control. Asian Pac J Trop Biomed [serial online] 2020 [cited 2023 Jun 5];10:341-2. Available from:

Female mosquitoes of several species require blood from warmblooded animals, including humans for the purpose of reproduction. In this process, several microbes residing in the salivary gland and midgut of mosquitoes also get transferred from one human individual to the other - a traditional model by which many vector-borne diseases (VBDs) get transmitted in the population through mosquitoes belonging to Anopheles, Aedes, Culex and other genera. Considering that VBDs are highly dependent on eco-climatic conditions of a particular location, the net holobiont (mosquito and its community of associated microorganisms)[1] of these medically-important mosquitoes possibly forms an “evolutionarily adapted microbial ecosystem”. Such an adapted microbial ecosystem in the mosquito’s salivary gland and midgut has been shown to be not only essential in their development and survival[2], but also can alter vector competence (ability to transmit pathogens in population) of mosquitoes[3]. This otherwise means that disruption of such a tripartite interaction (mosquito-microflora- pathogens) in an adapted holobiont complex might lead to changes in fitness, vectorial capacity, etc. of the mosquitoes, and pathogenic characteristics of different microbes (opportunists can turn pathogenic). In the tropical and subtropical regions of the globe, VBDs like malaria, dengue, chikungunya, Zika, etc. constitute one of the primary human health hazards and death. Controlling mosquito population (vector control) is considered as one of the finest ways to control VBDs. While traditional vector control strategies have several limitations, novel vector control approaches, viz., (i) reducing vector populations, and (ii) development and usage of mosquitoes refractory to pathogens of VBDs have shown great promises[4]. To this extent, recent advent of techniques for transforming mosquitoes refractory to pathogens (e.g. para-transgenesis, gene silencing, gene editing by CRISPR-Cas9, etc.) coupled with a gene drive[5] have been widely discussed and in some cases, vividly used for control of Anopheles and Aedes mosquitoes.

Amongst several approaches, turning mosquitoes that are vectors to different human microbial pathogens into refractory types has gained large momentum. For this, experiments involving two types of symbiotic Gram-negative bacteria that populate mosquito midgut (Wolbachia and Serratia) have yielded several interesting (and somehow contrasting) results. While Wolbachia can help inhibiting malaria parasite, Plasmodium infection in both Anopheles (Anopheles gambie and Anopheles stephensi[6],[7]) and Aedes (Aedes aegypti[8]) mosquitoes, evidences have been presented that Wolbachia can also enhance Plasmodium infection in Anopheles (Anopheles gambie[9]) and Aedes (Aedes fluviatilis[10]) in some cases[11]. Similarly, Serratia odorifera in one hand inhibits the development of Plasmodium but on the other hand enhances susceptibility of Aedes aegypti to dengue virus[12]. It seems therefore that in different holobiont complex, two different microbial pathogens (Wolbachia and Serratia) behave very differently in term of controlling either Plasmodium or dengue virus. Very similarly, mosquitoes also differ in transmitting different human microbial pathogens in different eco-climatic settings that possibly influence the composition of the holobiont. For example, the Japanese encephalitis virus is commonly transmitted by Culex mosquitoes in almost all the endemic settings but in Malaysia and India, in addition to Culex, Japanese encephalitis virus is transmitted by Aedes butleri[13] and Anopheles subpictus[14], respectively. Furthermore, Anopheles has also been shown to transmit an alphavirus, o’nyong-nyong[15]. All these results suggest the fact that mosquito holobionts form adaptive complexes that differ with mosquito species and eco-climatic conditions prevalent at the habitation of mosquitoes.

In mosquitoes, the CRISPR-Cas9 technique has been initiated relatively recently to disable infection to human pathogens, thereby preventing transmission of vector-borne diseases. For example, by knocking-out of the FREP1 (fibrinogen-related protein) gene, which is an essential factor of mosquito innate immune system required for maintaining immune-homeostasis (and thereby keeping the adapted mid-gut floral complex in harmony) in the malaria vector Anopheles gambiae by CRISPR-Cas9 method could help suppress the growth of Plasmodiuml [16]. Therefore, in a situation where Anopheles gambiae mosquitoes are FREP1 -deleted, due to altered immune homeostasis and disruption of adapted holobiont complex, existing opportunistic microbes in mosquito midgut/salivary gland might turn into pathogenic form for human and pose new threat to human health. It is therefore essential to develop novel vector control strategies for development of refractory mosquitoes to a particular pathogen with due care not to disrupt the adapted holobiont complex. This is necessary for maintaining homeostasis in mosquito midgut and/or salivary gland for better use of the technique in public health. A holistic view including surveillance on the composition of midgut and salivary gland microflora of the mosquito, geographic structure, in-depth analysis of eco-system surrounding mosquito habitation, reservoirs of the disease pathogen and bionomics of the mosquitoes should be taken into consideration before employing refractory mosquito techniques of vector control to improve public health.

Conflict of interest statement

We declare that there is no conflict of interest.

Authors’ contributions

USS conceived the idea, retrieved and analysed the data from publications and wrote the first draft of the manuscript. AD made necessary critical revisions for important intellectual content and wrote the final draft of the manuscript.

  References Top

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Dong Y, Manfredini F, Dimopoulos G. Implication of the mosquito midgut microbiota in the defense against malaria parasites. PLoS Pathog 2009; 5 (5): e1000423.  Back to cited text no. 2
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Wang S, Dos-Santos AL, Huang W, Liu KC, Oshaghi MA, Wei G, et al. Driving mosquito refractoriness to Plasmodium falciparum with engineered symbiotic bacteria. Science 2017; 357 (6358): 1399-1402.  Back to cited text no. 4
James S, Collins FH, Welkhoff PA, Emerson C, Godfray HC, Gottlieb M, et al. Pathway to deployment of gene drive mosquitoes as a potential biocontrol tool for elimination of malaria in Subsaharan Africa: Recommendations of a scientific working group. Am J Trop Med Hyg 2018; 98 (6_Suppl): 1-49.  Back to cited text no. 5
Hughes GL, Koga R, Xue P, Fukastu T, Rasgon JL. Wolbachia infections are virulent and inhibit the human malaria parasite Plasmodium falciparum in Anopheles gambiae. PLoS Pathog 2011; 7 (5): e1002043.  Back to cited text no. 6
Bian G, Joshi D, Dong Y, Lu P, Zhou G, Pan X, et al. Wolbachia invades Anopheles stephensi populations and induces refractoriness to Plasmodium infection. Science 2013; 340 (6133): 748-751.  Back to cited text no. 7
Moreira LA, Iturbe-Ormaetxe I, Jeffery JA, Lu G, Pyke AT, Hedges LM, et al. A Wolbachia symbiont in Aedes aegypti limits infection with dengue, Chikungunya, and Plasmodium. Cell 2009; 139 (7): 1268-1278.  Back to cited text no. 8
Hughes GL, Vega-Rodriguez J, Xue P, Rasgon JL. Wolbachia strain wAlbB enhances infection by the rodent malaria parasite Plasmodium berghei in Anopheles gambiae mosquitoes. Appl Environ Microbiol 2012; 78 (5): 1491-1495.  Back to cited text no. 9
Baton LA, Pacidonio EC, Goncalves DS, Moreira LA. wFlu: Characterization and evaluation of a native Wolbachia from the mosquito Aedes fluviatilis as a potential vector control agent. PLoS One 2013; 8 (3): e59619.  Back to cited text no. 10
Hughes GL, Rivero A, Rasgon JL. Wolbachia can enhance Plasmodium infection in mosquitoes: Implications for malaria control?. PLoS Pathog 2014; 10: e1004182.  Back to cited text no. 11
Apte-Deshpande A, Paingankar M, Gokhale MD, Deobagkar DN. Serratia odorìfera a midgut inhabitant of Aedes aegypti mosquito enhances its susceptibility to dengue-2 virus. PLoS One 2012; 7: e40401.  Back to cited text no. 12
Vythilingam I, Singh KI, Mahadevan S, Zaridah MS, Ong KK, Abidin MH, et al. Studies on Japanese encephalitis vector mosquitoes in Selangor, Malaysia. J Am Mosq Control Assoc 1993; 9 (4): 467-469.  Back to cited text no. 13
Thenmozhi V, Balaji T, Venkatasubramani K, Dhananjeyan KJ, Selvam A, Rajamannar V, et al. Role of Anopheles subpictus grassi in japanese encephalitis virus transmission in Tirunelveli, South India. Indian J Med Res 2016; 144 (3): 477-481.  Back to cited text no. 14
Pike A, Dimopoulos G. Genetic modification of Anopheles stephensi for resistance to multiple Plasmodium falciparum strains does not influence susceptibility to o’nyong‘nyong virus or insecticides, or Wolbachia- mediated resistance to the malaria parasite. PLoS One 2018; 13: e0195720.  Back to cited text no. 15
Dong Y, Simoes ML, Marois E, Dimopoulos G. CRISPR/Cas9-mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection. PLoS Pathog 2018; 14: e1006898.  Back to cited text no. 16

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