Abstract
Erythromycin is one of the most widely used antibiotics globally and is considered an emerging contaminant in wastewaters and environmental waters. The egg, larval, and pupal stages of the dengue vector Aedes aegypti L. reside and develop in aquatic environments. These mosquito stages may be exposed to compounds in the water, such as erythromycin. Aquatic stages of Ae. aegypti were reared in different concentrations of erythromycin which resulted in significant delay and decrease in eclosion of eggs and pupation of larvae (P < 0.05). Moreover, emergence of adults from pupae, larval survival, and adult female fecundity significantly decreased (P < 0.05). A few occurrences of hypopigmentation in larvae and blisters in adult mosquitoes were also observed. Interestingly, second-generation eggs, which were laid by adult female mosquitoes exposed to erythromycin during their aquatic stages, did not exhibit decreased levels of eclosion in the presence of erythromycin. These results reveal that long-term erythromycin exposure disrupts the Ae. aegypti life cycle by decreasing survival and delaying progression throughout different life stages. However, this study demonstrates that Ae. aegypti can rapidly acquire significant tolerance to the emerging environmental contaminant erythromycin within two generations.
Similar content being viewed by others
References
Asano, T. (2013). Enzymes for melanin synthesis in insect cuticle. Hikaku seiri seikagaku (Comparative Physiology and Biochemistry). https://doi.org/10.3330/hikakuseiriseika.30.106.
Attardo, G. M., Hansen, I. A., & Raikhel, A. S. (2005). Nutritional regulation of vitellogenesis in mosquitoes: implications for anautogeny. Insect Biochemistry and Molecular Biology, 35, 661–675.
Banerjee, S., Mohan, S., Saha, N., Mohanty, S. P., Goutam, K., & Saha, G. A. (2015). Pupal productivity & nutrient reserves of Aedes mosquitoes breeding in sewage drains and other habitats of Kolkata, India: implications for habitat expansion & vector management. The Indian Journal of Medical Research, 142(Suppl 1), S87–S94.
Barrera, R., Amador, M., Diaz, A., Smith, J., Munoz-Jordan, J. L., & Rosario, Y. (2008). Unusual productivity of Aedes aegypti in septic tanks and its implications for dengue control. Medical and Veterinary Entomology, 22(1), 62–69. https://doi.org/10.1111/j.1365-2915.2008.00720.x.
Boxall, A.B.A. (2012). New and emerging water pollutants arising from agriculture. Resource document. Organisation for Economic Cooperation and Development. https://www.oecd.org/tad/sustainable-agriculture/49848768.pdf. Accessed 21 March 2017.
Boxall, A. B. A., Fogg, L. A., Kay, P., Blackwell, P. A., Pemberton, E. J., & Croxford, A. (2003). Veterinary medicines in the environment. Reviews of Environmental Contamination and Toxicology, 180, 1–91.
Centers for Disease Control and Prevention. (2016). Mosquito life cycle. Accessed at https://www.cdc.gov/zika/pdfs/mosquitolifecycle.pdf.
Chouaia, B., Rossi, P., Epis, S., Mosca, M., Ricci, I., Damiani, C., Ulissi, U., Crotti, E., Daffonchio, D., Bandi, C., & Favia, G. (2012). Delayed larval development in Anopheles mosquitoes deprived of Asaia bacterial symbionts. BMC Microbiology, 12, S2.
Chouin-Carneiro, T., Vega-Rua, A., Vazeille, M., Yebakima, A., Girod, R., Goindin, D., Dupont-Rouzeyrol, M., Lourenço-de-Oliveira, R., & Failloux, A. B. (2016). Differential susceptibilities of Aedes aegypti and Aedes albopictus from the Americas to Zika virus. PLoS Neglected Tropical Diseases. https://doi.org/10.1371/journal.pntd.0004543.
Coon, K. L., Vogel, K. J., Brown, M. R., & Strand, M. R. (2014). Mosquitoes rely on their gut microbiota for development. Molecular Ecology. https://doi.org/10.1111/mec.12771.
Coon, K. L., Brown, M. R., & Strand, M. R. (2016a). Mosquitoes host communities of bacteria that are essential for development but vary greatly between local habitats. Molecular Ecology. https://doi.org/10.1111/mec.13877.
Coon, K. L., Brown, M. R., & Strand, M. R. (2016b). Gut bacteria differentially affect egg production in the anautogenous mosquito Aedes aegypti and facultatively autogenous mosquito Aedes atropalpus (Diptera: Culicidae). Parasites & Vectors. https://doi.org/10.1186/s13071-016-1660-9.
Couret, J., Dotson, E., & Benedict, M. Q. (2014). Temperature, larval diet, and density effects on development rate and survival of Aedes aegypti (Diptera: Culicidae). PLoS One, 9(2), e87468. https://doi.org/10.1371/journal.pone.0087468.
Dada, N., Jumas-Bilak, E., Manguin, S., Seidu, R., Stenström, T. A., & Overgaard, H. J. (2014). Comparative assessment of the bacterial communities associated with Aedes aegypti larvae and water from domestic water storage containers. Parasites & Vectors. https://doi.org/10.1186/1756-3305-7-391.
Danks, H. D. (2000). Measuring and reporting life-cycle duration in insects and arachnids. European Journal of Entomology, 97, 285–303.
David, J. P., Coissac, E., Melodelima, C., Poupardin, R., Riaz, M. A., Chandor-Proust, A., & Reynaud, S. (2010). Transcriptome response to pollutants and insecticides in the dengue vector Aedes aegypti using next-generation sequencing technology. BMC Genomics, 11, 216.
David, M. R., dos Santos, L. M. B., Vicente, A. C. P., & Maciel-de-Freitas, R. (2016). Effects of environment, dietary regime and ageing on the dengue vector microbiota: Evidence of a core microbiota throughout Aedes aegypti lifespan. Memórias do Instituto Oswaldo Cruz, 111(9), 577–587.
Dinh, Q. T., Alliot, F., Moreau-Guigon, E., Eurin, J., Chevreuil, M., & Labadie, P. (2011). Measurement of trace levels of antibiotics in river water using on-line enrichment and triple-quadrupole LC-MS/MS. Talanta, 85(3), 1238–1245.
El-Nahhal, Y., & El-Dahdouh, N. (2015). Toxicity of amoxicillin and erythromycin to fish and mosquitoes. Ecotoxicology and Environmental Contamination, 10(1), 13–21.
Ferdig, M. T., Taft, A. S., Smartt, C. T., Lowenberger, C. A., Li, J., Zhang, J., & Christensen, B. M. (2000). Aedes aegypti dopa decarboxylase: gene structure and regulation. Insect Molecular Biology, 9(3), 231–239.
Finland, M., Garner, C., Wilcox, C., & Sabath, L. D. (1976). Susceptibility of “Enterobacteria” to penicillins, cephalosporins, lincomycins, erythromycin, and rifampin. Journal of Infectious Diseases, 134(Suppl), S75–S96.
Gaio Ade, O., Gusmão, D. S., Santos, A. V., Berbert-Molina, M. A., Pimenta, P. F., & Lemos, F. J. (2011). Contribution of midgut bacteria to blood digestion and egg production in Aedes aegypti (Diptera: Culicidae) (L.). Parasites & Vectors. https://doi.org/10.1186/1756-3305-4-105.
Gillett, J. D., Roman, E. A., & Phillips, V. (1977). Erratic hatching in Aedes eggs: a new interpretation. Proceedings of the Royal Society of London B, 196, 223–232.
Gozlan, I., Koren, I., & Avisar, D. (2016). Identification, mechanisms and kinetics of macrolide degradation product formation under controlled environmental conditions. Journal of Environmental Analytical Chemistry, 3, 171. https://doi.org/10.4172/2380-2391.1000171.
Haight, T., & Finland, M. (1952). Observations on mode of action of erythromycin. Experimental Biology and Medicine, 81(1), 188–193.
Hopkins, T. L., & Kramer, K. J. (1992). Insect cuticle sclerotization. Annual Review of Entomology, 37, 273–302.
Imam, H., Zarnigar, Sofi, G., & Seikh, A. (2014). The basic rules and methods of mosquito rearing (Aedes aegypti). Tropical Parasitology, 4(1), 53–55. https://doi.org/10.4103/2229-5070.129167.
Jessick, A. M., Moorman, T. B., & Coats, J. R. (2013). Fate of erythromycin in sediment-containing surface water microcosms: how does aged erythromycin in sediment influence bioavailability? In G. Cobb et al. (Eds.), Evaluating veterinary pharmaceutical behavior in the environment, ACS symposium series. Washington, DC: American Chemical Society.
Jiang, J. J., Lee, C. L., Fang, M. D., Tu, B. W., & Liang, Y. J. (2015). Impacts of emerging contaminants on surrounding aquatic environment from a youth festival. Environmental Science and Technology, 49(2), 792–799.
Johnson, A. C., Keller, V., Dumont, E., & Sumpter, J. P. (2015). Assessing the concentrations and risks of toxicity from the antibiotics ciprofloxacin, sulfamethoxazole, trimethoprim and erythromycin in European rivers. Science of the Total Environment, 511, 747–755.
Kaipainen, W. J., & Faine, S. (1954). Toxicity of erythromycin. Nature. https://doi.org/10.1038/174969b0.
Kaplan, S. (2013). Review: pharmacological pollution in water. Critical Reviews in Environmental Science and Technology, 43(10), 1074–1116.
Kasprzyk-Hordern, B., Dinsdale, R. M., & Guwy, A. J. (2009). The removal of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs during wastewater treatment and its impact on the quality of receiving waters. Water Research, 43(2), 363–380.
Kirst, H. A. (2010). The spinosyn family of insecticides: realizing the potential of natural products research. Journal of Antibiotics (Tokyo), 63(3), 101–111.
Margam, V. M., Gelman, D. B., & Palli, S. R. (2006). Ecdysteroid titers and developmental expression of ecdysteroid-regulated genes during metamorphosis of the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae). Journal of Insect Physiology, 52(6), 558–568.
Mazzei, T., Mini, E., Novelli, A., & Periti, P. (1993). Chemistry and mode of action of macrolides. The Journal of Antimicrobrial Chemotherapy, 31(Suppl C), 1–9.
McArdell, C. S., Molnar, E., Suter, M. J., & Giger, W. (2003). Occurrence and fate of macrolide antibiotics in wastewater treatment plants and in the Glatt Valley watershed, Switzerland. Environmental Science and Technology, 37(24), 5479–5486.
Merritt, R. W., Dadd, R. H., & Walker, E. D. (1992). Feeding behavior, natural food, and nutritional relationships of larval mosquitoes. Annual Review of Entomology, 37, 349–376.
Minard, G., Mavingui, P., & Moro, C. V. (2013). Diversity and function of bacterial microbiota in the mosquito holobiont. Parasites & Vectors. https://doi.org/10.1186/1756-3305-6-146.
Minh, T. B., Leung, H. W., Loi, I. H., Chan, W. H., So, M. K., Mao, J. Q., Choi, D., Lam, J. C., Zheng, G., Martin, M., Lee, J. H., Lam, P. K., & Richardson, B. J. (2009). Antibiotics in the Hong Kong metropolitan area: ubiquitous distribution and fate in Victoria Harbour. Marine Pollution Bulletin, 58(7), 1052–1062.
Nasir, S., Jabeen, F., Abbas, S., Nasir, I., & Debboun, M. (2017). Effect of climatic conditions and water bodies on population dynamics of the dengue vector, Aedes aegypti (Diptera: Culicidae). Journal of Arthropod-Borne Diseases, 11(1), 50–59.
Nie, X. P., Liu, B. Y., Yu, H. J., Liu, W. Q., & Yang, Y. F. (2013). Toxic effects of erythromycin, ciprofloxacin and sulfamethoxazole exposure to the antioxidant system in Pseudokirchneriella subcapitata. Environmental Pollution, 172, 23–32.
Ocampo, P. S., Lázár, V., Papp, B., Arnoldini, M., Abel zur Wiesch, P., Busa-Fekete, R., Fekete, G., Pál, C., Ackermann, M., & Bonhoeffer, S. (2014). Antagonism between bacteriostatic and bactericidal antibiotics is prevalent. Antimicrobial Agents and Chemotherapy, 58(8), 4573–4582.
Panditi, V. R., Batchu, S. R., & Gardinali, P. R. (2013). Online solid-phase extraction–liquid chromatography–electrospray–tandem mass spectrometry determination of multiple classes of antibiotics in environmental and treated waters. Analytical and Bioanalytical Chemistry. https://doi.org/10.1007/s00216-013-6863-8.
Pankey, G. A., & Sabath, L. D. (2004). Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections. Clinical Infectious Diseases, 38(6), 864–870.
Pennington, M. J., Rivas, N. G., Prager, S. M., Walton, W. E., & Trumble, J. T. (2015). Pharmaceuticals and personal care products alter the holobiome and development of a medically important mosquito. Environmental Pollution, 203, 199–207.
Ponnusamy, L., Böröczky, K., Wesson, D. M., Schal, C., & Apperson, C. S. (2011). Bacteria stimulate hatching of yellow fever mosquito eggs. PLoS One, 6(9), e24409.
Poupardin, R., Reynaud, S., Strode, C., Ranson, H., Vontas, J., & David, J. P. (2008). Cross-induction of detoxification genes by environmental xenobiotics and insecticides in the mosquito Aedes aegypti: impact on larval tolerance to chemical insecticides. Insect Biochemistry and Molecular Biology, 38(5), 540–551.
Price, D. P., Schilkey, F. D., Ulanov, A., & Hansen, I. A. (2015). Small mosquitoes, large implications: crowding and starvation affects gene expression and nutrient accumulation in Aedes aegypti. Parasites & Vectors. https://doi.org/10.1186/s13071-015-0863-9.
Ramasamy, R., Surendran, S. N., Jude, P. J., Dharshini, S., & Vinobaba, M. (2011). Larval development of Aedes aegypti and Aedes albopictus in peri-urban brackish water and its implications for transmission of arboviral diseases. PLoS Neglected Tropical Diseases, 5(11), e1369. https://doi.org/10.1371/journal.pntd.0001369.
Riaz, M. A., Poupardin, R., Reynaud, S., Strode, C., Ranson, H., & David, J. P. (2009). Impact of glyphosate and benzo[a]pyrene on the tolerance of mosquito larvae to chemical insecticides. Role of detoxification genes in response to xenobiotics. Aquatic Toxicology, 93(1), 61–69.
Rodrigues, S., Antunes, S. C., Correia, A. T., & Nunes, B. (2016). Acute and chronic effects of erythromycin exposure on oxidative stress and genotoxicity parameters of Oncorhynchus mykiss. Science of the Total Environment, 545(546), 591–600.
Sauvé, S., & Desrosiers, M. (2014). A review of what is an emerging contaminant. Chemistry Central Journal, 8, 15.
Schlaeger, D. A., Fuchs, M. S., & Kang, S. H. (1974). Ecdysone-mediated stimulation of dopa-decarboxylase activity and its relationship to ovarian development in Aedes aegypti. Journal of Cell Biology, 61(2), 454–465.
Serisier, D. J., Martin, M. L., McGuckin, M. A., Lourie, R., Chen, A. C., Brain, B., Biga, S., Schlebusch, S., Dash, P., & Bowler, S. D. (2013). Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA, 309(12), 1260–1267.
Soares, M. P., Silva-Torres, F. A., Elias-Neto, M., Nunes, F. M., Simões, Z. L., & Bitondi, M. M. (2011). Ecdysteroid-dependent expression of the tweedle and peroxidase genes during adult cuticle formation in the honey bee, Apis mellifera. PLoS One. https://doi.org/10.1371/journal.pone.0020513.
Stackelberg, P. E., Furlong, E. T., Meyer, M. T., Zaugg, S. D., Henderson, A. K., & Reissman, D. B. (2004). Persistence of pharmaceutical compounds and other organic wastewater contaminants in a conventional drinking-water-treatment plant. Science of the Total Environment, 329(1–3), 99–113.
Telang, A., Li, Y., Noriega, F. G., & Brown, M. R. (2006). Effects of larval nutrition on the endocrinology of mosquito egg development. Journal of Experimental Biology, 209(Pt 4), 645–655.
Telang, A., Frame, L., & Brown, M. R. (2007). Larval feeding duration affects ecdysteroid levels and nutritional reserves regulating pupal commitment in the yellow fever mosquito Aedes aegypti (Diptera: Culicidae). Journal of Experimental Biology, 210(Pt 5), 854–864.
Tolls, J. (2001). Sorption of veterinary pharmaceuticals in soils: a review. Environmental Science & Technology, 37, 3397–3406.
Tun-Lin, W., Burkot, T. R., & Kay, B. H. (2000). Effects of temperature and larval diet on development rates and survival of the dengue vector Aedes aegypti in North Queensland, Australia. Medical and Veterinary Entomology, 14(1), 31–37.
Unger, L., & Kisch, A. (1958). Observations on bacteriostatic and bactericidal action of erythromycin. Experimental Biology and Medicine, 98(1), 176–178.
Van Boeckel, T. P., Gandra, S., Ashok, A., Caudron, Q., Grenfell, B. T., Levin, S. A., & Laxminarayan, R. (2014). Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. The Lancet Infectious Diseases, 14(8), 742–750.
Viluksela, M., Hanhijärvi, H., Husband, R. F., Kosma, V. M., Collan, Y., & Männistö, P. T. (1988). Comparative liver toxicity of various erythromycin derivatives in animals. Journal of Antimicrobial Chemotherapy, 21(Suppl D), 9–27.
World Health Organization. (2009). Dengue: guidelines for diagnosis, treatment, prevention and control. Geneva: World Health Organization.
Xu, W. H., Zhang, G., Zou, S. C., Li, X. D., & Liu, Y. C. (2007). Determination of selected antibiotics in the Victoria Harbour and the Pearl River, South China using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Environmental Pollution, 145(3), 672–679.
Yadav, K. K., Bora, A., Datta, S., Chandel, K., Gogoi, H. K., Prasad, G. B., & Veer, V. (2015). Molecular characterization of midgut microbiota of Aedes albopictus and Aedes aegypti from Arunachal Pradesh, India. Parasites & Vectors. https://doi.org/10.1186/s13071-015-1252-0.
Yamany, A. S., & Adham, F. K. (2014). The effect of larval and adult nutrition on survival and fecundity of dengue vector Aedes albopictus Skuse (Diptera: Culicidae). Journal of the Egyptian Society of Parasitology, 44(2), 447–454.
Zhang, T., & Li, B. (2011). Occurrence, transformation, and fate of antibiotics in municipal wastewater treatment plants. Critical Reviews in Environmental Science and Technology, 41(11), 951–998.
Acknowledgements
The authors would like to acknowledge Professor Celia M. Austria for her insights on this research and for providing logistic assistance during the experimentation.
Author information
Authors and Affiliations
Contributions
Conceived and designed the experiments: PMM. Performed the experiments: MLC PMM. Analyzed the data: MLC PMM JLA. Wrote the paper: MLC PMM JLA.
Corresponding author
Rights and permissions
About this article
Cite this article
Calma, M.L., Asis, J.L.B. & Medina, P.M.B. Erythromycin Exposure Disrupts the Life Cycle Stages of Aedes aegypti L. (Diptera: Culicidae). Water Air Soil Pollut 229, 159 (2018). https://doi.org/10.1007/s11270-018-3811-4
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11270-018-3811-4