Survival effects of antibiotic exposure during the larval and adult stages in the West Nile virus vector Culex pipiens

Abstract

The ability of mosquitoes to transmit a pathogen is affected, among other factors, by their survival rate, which is partly modulated by their microbiota. Mosquito microbiota is acquired during the larval phase and modified during their development and adult feeding behavior, being highly dependent on environmental factors. Pharmaceutical residues including antibiotics are widespread pollutants potentially being present in mosquito breeding waters likely affecting their microbiota. Here, we used Culex pipiens mosquitoes to assess the impact of antibiotic exposure during the larval and adult stages on the survival rate of adult mosquitoes. Wild-collected larvae were randomly assigned to two treatments: larvae maintained in water supplemented with antibiotics and control larvae. Emerged adults were subsequently assigned to each of two treatments, fed with sugar solution with antibiotics and fed only with sugar solution (controls). Larval exposure to antibiotics significantly increased the survival rate of adult females that received a control diet. In addition, the effect of adult exposure to antibiotics on the survival rate of both male and female mosquitoes depended on the number of days that larvae fed ad libitum in the laboratory before emergence. In particular, shorter larval ad libitum feeding periods reduced the survival rate of antibiotic-treated adult mosquitoes compared with those that emerged after a longer larval feeding period. These differences were not found in control adult mosquitoes. Our results extend the current understanding of the impact of antibiotic exposure of mosquitoes on a key component of vectorial capacity, that is the vector survival rate.

Key words： antibiotics; avian malaria; microbiota; mosquitoes; vector competence; vector survival

References

1 Ahmed,A.M., Baggott, S.L., Maingon,R. and Hurd,H. (2002) The costs of mounting an immune response are reflected in the reproductive fitness of the mosquito Anopheles gambiae. Oikos, 97, 371–377.

2 Cansado-Utrilla,C., Zhao, S.Y., McCall,P.J., Coon,K.L. and Hughes, G.L. (2021) The microbiome and mosquito vectorial capacity: rich potential for discovery and translation. Microbiome, 9, 111.

3 Caragata,E.P., Rancès, E., Hedges,L.M., Gofton,A.W., Johnson, K.N., O'Neill,S.L. et al. (2013) Dietary cholesterol modulates pathogen blocking by Wolbachia. PLoS Pathogens, 9, e1003459.

4 Carlson,J.S., Short,S.M., Angleró-Rodríguez,Y.I. and Dimopoulos,G. (2020) Larval exposure to bacteria modulates arbovirus infection and immune gene expression in adult Aedes aegypti. Developmental and Comparative Immunology, 104, 103540.

5 Carvajal-Lago,L., Ruiz-López, M.J., Figuerola,J. and Martínez-de la Puente,J. (2021) Implications of diet on mosquito life history traits and pathogen transmission. Environmental Research, 195, 110893.

6 Chabanol,E., Behrends, V., Prévot,G., Christophides,G.K. and Gendrin, M. (2020) Antibiotic treatment in Anopheles coluzzii affects carbon and nitrogen metabolism. Pathogens, 9, 679.

7 Chouaia,B., Rossi,P., Epis,S., Mosca, M., Ricci,I., Damiani,C. et al. (2012) Delayed larval development in Anopheles mosquitoes deprived of Asaia bacterial symbionts. BMC Microbiology, 12, S2.

8 Contreras,E., Masuyer, G., Qureshi,N., Chawla,S., Dhillon, H.S., Lee,H.L. et al. (2019) A neurotoxin that specifically targets Anopheles mosquitoes. Nature Communications, 10, 2869.

9 Coon,K.L., Vogel,K.J., Brown,M.R. and Strand, M.R. (2014) Mosquitoes rely on their gut microbiota for development. Molecular Ecology, 23, 2727–2739.

10 Danchin,A. and Braham, S. (2017) Coenzyme B12 synthesis as a baseline to study metabolite contribution of animal microbiota. Microbial Biotechnology, 10, 688–701.

11 Dickson,L.B., Jiolle, D., Minard,G., Moltini-Conclois,I., Volant, S., Ghozlane,A. et al. (2017) Carryover effects of larval exposure to different environmental bacteria drive adult trait variation in a mosquito vector. Science Advances, 3, e1700585.

12 Day,J.F. and Van Handel, E. (1986) Differences between the nutritional reserves of laboratory-maintained and field-collected adult mosquitoes. Journal of the American Mosquito Control Association, 2, 154–157.

13 Dong,Y., Manfredini, F. and Dimopoulos,G. (2009) Implication of the mosquito midgut microbiota in the defense against malaria parasites. PLoS Pathogens, 5, e1000423.

14 Endersby-Harshman,N.M., Axford, J.K. and Hoffmann,A.A. (2019) Environmental concentrations of antibiotics may diminish Wolbachia infections in Aedes aegypti (Diptera: Culicidae). Journal of Medical Entomology, 56, 1078–1086.

15 Engler,O., Savini, G., Papa,A., Figuerola,J., Groschup, M., Kampen,H. et al. (2013) European surveillance for west Nile virus in mosquito populations. International Journal of Environmental Research and Public Health, 10, 4869–4895.

16 Folly,A.J., Dorey-Robinson, D., Hernández-Triana, L.M., Phipps,L.P. and Johnson,N. (2020) Emerging threats to animals in the United Kingdom by arthropod-borne diseases. Frontiers in Veterinary Science, 7, 20.

17 Gabrieli,P., Caccia, S., Varotto-Boccazzi,I., Arnoldi,I., Barbieri, G., Comandatore,F. et al. (2021) Mosquito trilogy: microbiota, immunity and pathogens, and their implications for the control of disease transmission. Frontiers in Microbiology, 12, 630438.

18 Gaio,A.O., Gusmão, D.S., Santos,A.V., Berbert-Molina,M.A., Pimenta, P.F.P. and Lemos,F.J.A. (2011) Contribution of midgut bacteria to blood digestion and egg production in Aedes aegypti (Diptera: Culicidae) (L.). Parasites & Vectors, 4, 105.

19 Garrett-Jones,C. (1964) Prognosis for interruption of malaria transmission through assessment of the mosquito's vectorial capacity. Nature, 204, 1173–1175.

20 Gendrin,M., Rodgers, F.H., Yerbanga,R.S., Ouédraogo,J.B., Basáñez, M.G., Cohuet,A. et al. (2015) Antibiotics in ingested human blood affect the mosquito microbiota and capacity to transmit malaria. Nature Communications, 6, 5921.

21 Giraud,É., Varet, H., Legendre,R., Sismeiro,O., Aubry,F., Dabo,S. et al. (2022) Mosquito-bacteria interactions during larval development trigger metabolic changes with carry-over effects on adult fitness. Molecular Ecology, 31, 1444–1460.

22 Gómez-Govea,M.A., Ramírez-Ahuja,M.L., Contreras-Perera,Y., Jiménez-Camacho, A.J., Ruiz-Ayma,G., Villanueva-Segura,O.K. et al. (2022) Suppression of midgut microbiota impact pyrethroid susceptibility in Aedes aegypti. Frontiers in Microbiology, 13, 761459.

23 Guégan,M., Tran Van, V., Martin,E., Minard,G., Tran,F.H., Fel,B. et al. (2020) Who is eating fructose within the Aedes albopictus gut microbiota? Environmental Microbiology, 22, 1193–1206.

24 Gutiérrez-López,R., Martínez-de la Puente,J., Gangoso,L., Soriguer, R. and Figuerola,J. (2020) Plasmodium transmission differs between mosquito species and parasite lineages. Parasitology, 147, 441–447.

25 Ha,Y.R., Jeong,S.J., Jang,C.W., Chang, K.S., Kim,H.W., Cho,S.H. et al. (2021) The effects of antibiotics on the reproductive physiology targeting ovaries in the Asian tiger mosquito, Aedes albopictus. Entomological Research, 51, 65–73.

26 Haba,Y. and McBride, L. (2022) Origin and status of Culex pipiens mosquito ecotypes. Current Biology, 32, R237–R246.

27 Kassambara,A., Kosinski, M. and Biecek,P. (2021) Survminer: drawing survival curves using ‘ggplot2’. R package version 0.4.9. https://CRAN.R-project.org/package=survminer

28 Lefèvre,T., Vantaux, A., Dabiré,K.R., Mouline,K. and Cohuet, A. (2013) Non-genetic determinants of mosquito competence for malaria parasites. PLoS Pathogens, 9, e1003365.

29 Lindh,J.M., Borg-Karlson, A.K. and Faye,I. (2008) Transstadial and horizontal transfer of bacteria within a colony of Anopheles gambiae (Diptera: Culicidae) and oviposition response to bacteria-containing water. Acta Tropica, 107, 242–250.

30 Maghsodian,Z., Sanati, A.M., Mashifana,T., Sillanpää,M., Feng, S., Nhat,T. et al. (2022) Occurrence and distribution of antibiotics in the water, sediment, and biota of freshwater and marine environments: a review. Antibiotics (Basel, Switzerland), 11, 1461.

31 Martínez-de la Puente,J., Gutiérrez-López,R. and Figuerola,J. (2018) Do avian malaria parasites reduce vector longevity? Current Opinion in Insect Science, 28, 113–117.

32 Martínez-de la Puente,J., Gutiérrez-López,R., Díez-Fernández,A., Soriguer,R.C., Moreno-Indias, I. and Figuerola,J. (2021) Effects of mosquito microbiota on the survival cost and development success of avian Plasmodium. Frontiers in Microbiology, 11, 562220.

33 Merritt,R.W., Dadd,R.H. and Walker,E.D. (1992) Feeding behavior, natural food, and nutritional relationships of larval mosquitoes. Annual Review of Entomology, 37, 349–376.

34 Mutuku,C., Gazdag, Z. and Melegh,S. (2022) Occurrence of antibiotics and bacterial resistance genes in wastewater: resistance mechanisms and antimicrobial resistance control approaches. World Journal of Microbiology and Biotechnology, 38, 152.

35 Muturi,E.J., Dunlap, C., Ramirez,J.L., Rooney,A.P. and Kim, C.H. (2019) Host blood-meal source has a strong impact on gut microbiota of Aedes aegypti. FEMS Microbiology Ecology, 95, fiy213.

36 Ndiva Mongoh,M., Hearne, R., Dyer,N.W. and Khaitsa,M.L. (2008) The economic impact of West Nile virus infection in horses in the North Dakota equine industry in 2002. Tropical Animal Health and Production, 40, 69–76.

37 Neff,E. and Dharmarajan, G. (2021) The direct and indirect effects of copper on vector-borne disease dynamics. Environmental Pollution, 269, 116213.

38 Pendell,D.L., Lusk,J.L., Marsh,T.L., Coble, K.H. and Szmania,S.C. (2016) Economic assessment of zoonotic diseases: an illustrative study of Rift Valley Fever in the United States. Transboundary and Emerging Diseases, 63, 203–214.

39 Qing,W., Zhijing, X., Guangfu,Y., Fengxia,M., Qiyong, L., Zhong,Z. et al. (2020) Variation in the microbiota across different developmental stages of Aedes albopictus is affected by ampicillin exposure. MicrobiologyOpen, 9, 1162–1174.

40 R Core Team. (2022) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/

41 Ramirez,J.L., Short,S.M., Bahia,A.C., Saraiva, R.G., Dong,Y., Kang,S. et al. (2014) Chromobacterium Csp_P reduces malaria and dengue infection in vector mosquitoes and has entomopathogenic and in vitro anti-pathogen activities. PLoS Pathogens, 10, e1004398.

42 Samaddar,N., Paul,A., Chakravorty,S., Chakraborty,W., Mukherjee, J., Chowdhuri,D. et al. (2011) Nitrogen fixation in Asaia sp. (family Acetobacteraceae). Current Microbiology, 63, 226–231.

43 Santiago-Alarcon,D., Palinauskas, V. and Schaefer,H.M. (2012) Diptera vectors of avian Haemosporidian parasites: untangling parasite life cycles and their taxonomy. Biological Reviews of the Cambridge Philosophical Society, 87, 928–964.

44 Santos,N.A.C., Magi,F.N., Andrade,A.O., Bastos,A.S., Pereira, S.D.S., Medeiros,J.F. et al. (2022) Assessment of antibiotic treatment on Anopheles darlingi survival and susceptibility to Plasmodium vivax. Frontiers in Microbiology, 13, 971083.

45 Sarma,D.K., Kumar,M., Dhurve,J., Pal, N., Sharma,P., James,M.M. et al. (2022) Influence of host blood meal source on gut microbiota of wild caught Aedes aegypti, a dominant arboviral disease vector. Microorganisms, 10, 332.

46 Schaffner,E., Angel,G., Geoffroy,B., Hervy, J.P., Rhaiem,A. and Brunhes,J. (2001) The Mosquitoes of Europe: An Identification and Training Programme. Paris (FRA); Montpellier: IRD; EID, 1 CD ROM. (Didactiques).

47 Souza,R.S., Virginio, F., Riback,T.I.S., Suesdek,L., Barufi, J.B. and Genta,F.A. (2019) Microorganism-based larval diets affect mosquito development, size and nutritional reserves in the yellow fever mosquito Aedes aegypti (Diptera: Culicidae). Frontiers in Physiology, 10, 152.

48 Steyn,A., Roets,F. and Botha,A. (2016) Yeasts associated with Culex pipiens and Culex theileri mosque larvae and the effect of selected yeast strains on the ontogeny of Culex pipiens. Microbial Ecology, 71, 747–760.

49 Therneau,T. (2022) A package for survival analysis in R. R package version 3.3-1. https://CRAN.R-project.org/package=survival

50 Tikhe,C.V. and Dimopoulos, G. (2022) Phage therapy for mosquito larval control: a proof-of-principle study. Mbio, 13, e0301722.

51 Wang,Y., Eum,J.H., Harrison,R.E., Valzania,L., Yang,X., Johnson,J.A. et al. (2021) Riboflavin instability is a key factor underlying the requirement of a gut microbiota for mosquito development. Proceedings of the National Academy of Sciences USA, 118, e2101080118.

52 WHO, World Health Organization. (2020) Vector-borne diseases. https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases

53 Wilkinson,J.L., Boxall, A.B.A., Kolpin,D.W., Leung,K.M.Y., Lai,R.W.S., Galbán-Malagón,C. et al. (2022) Pharmaceutical pollution of the world's rivers. Proceedings of the National Academy of Sciences USA, 119, e2113947119.