Evaluating the potential toxicity of ampicillin using Drosophila melanogaster as a model organism
Asem Sanjit Singh1, Dhruv Pathak1, Sakshi Jain1
1Developmental and Biomedical Genetics Laboratory, Department of Developmental Biology and Genetics, Indian Institute of Science, Bengaluru 560012, India.
Abstract:
Antibiotic resistance is an indispensable threat facing in the present era. However, the studies on long term and trans-generational effects of using drugs or antibiotics on living organisms are scarce. Emphasizing the necessity to address such problems, this study investigated the potential effects of antibiotic, ampicillin (AMP) stress on the physiology of Drosophila melanogaster across multiple generations with mechanistic details. We evaluated the larval feeding behavior, fertility, cell viability in ovary and testis, longevity, expression of methylation-related genes (dDnmt2 and dMBD2/3), and antimicrobial peptide production. Larvae exposed to AMP exhibited increased mouth hook movement, indicating altered behaviour. AMP stress significantly reduced fertility across generations, with eclosion counts decreasing notably in F3 and F4 generations compared to controls. Moreover, AMP-treated flies showed decreased cell viability in ovary and testis, leading to impaired reproductive function. AMP exposure shortened the mean lifespan of flies and upregulated the expression of apoptosis-related gene p53 in females. However, there was no significant difference in p53 expression in males. Additionally, AMP stress caused a significant decrease in Drosomycin expression in treated males, while no significant changes were observed in Drosocin and Metchnikowin. In treated females, Drosocin and Drosomycin expression increased significantly, whereas the increase in Metchnikowin was not significant. The study also revealed downregulation of methylation-related genes (dDnmt2 and dMBD2/3) in AMP-treated female flies which was normalised in the rescue flies suggesting disrupted epigenetic mechanisms. Overall, the findings highlighted the importance of evaluating the trans-generational impacts of AMP stress on Drosophila physiology and gene expression, particularly in reproductive function and epigenetic regulation. The study of the impact of widely used antibiotic, AMP on model organism, Drosophila (model organism known for its genetic similarity to human), will help in predicting potential impacts on higher organisms and human. The finding would ultimately promote proper use of antibiotics and use of alternative medicine.
Insights
Ampicillin (AMP) exposure harms fruit fly reproduction and lifespan across generations, affecting gene expression and epigenetic regulation. This highlights the need for caution with antibiotic use and exploring alternatives.
Area of Science:
- Environmental Science
- Genetics
- Toxicology
Background:
- Antibiotic resistance is a growing global health threat.
- Long-term and trans-generational effects of antibiotic exposure are understudied.
- Ampicillin (AMP) is a widely used antibiotic with potential unknown long-term impacts.
Purpose of the Study:
- To investigate the multi-generational physiological and molecular effects of ampicillin (AMP) stress in Drosophila melanogaster.
- To elucidate the mechanistic details of AMP's impact on fertility, behavior, and gene expression.
- To assess the trans-generational consequences of antibiotic exposure on reproductive health and epigenetic regulation.
Main Methods:
- Drosophila melanogaster were exposed to ampicillin (AMP) across multiple generations.
- Evaluated larval feeding behavior, fertility (eclosion rates), lifespan, and reproductive organ cell viability.
- Analyzed the expression of apoptosis-related gene p53, methylation-related genes (dDnmt2, dMBD2/3), and antimicrobial peptides (Drosomycin, Drosocin, Metchnikowin).
Main Results:
- AMP exposure altered larval feeding behavior and significantly reduced fertility and lifespan across generations.
- Decreased ovarian and testicular cell viability impaired reproductive function; p53 expression upregulated in females.
- Downregulation of epigenetic genes (dDnmt2, dMBD2/3) observed in females, suggesting disrupted epigenetic mechanisms.
Conclusions:
- Ampicillin (AMP) stress induces significant trans-generational adverse effects on Drosophila melanogaster physiology, particularly impacting reproduction and lifespan.
- Findings indicate potential disruptions in epigenetic regulation and increased apoptosis, highlighting the need for careful antibiotic stewardship.
- This study provides insights into the broader implications of antibiotic use on complex organisms, informing strategies for responsible antibiotic application and alternative therapies.
