The spread of antimicrobial resistance caused by non-antibiotic pharmaceuticals

Antibiotic resistance poses a major threat to public health. It is estimated that antibiotic-resistant infections will cause millions of death with an economy loss of $100 trillion by 2050 if current trends continue. Antibiotic resistance that evolved from mutations could be transferred from environmental bacteria to human pathogens through a process known as horizontal gene transfer.

Overuse and misuse of antibiotics are generally recognised as the key factors contributing to the spread of antibiotic resistance. However, whether non-antibiotic pharmaceuticals and personal care products can mediate the spread of antibiotic resistance via mutation and/or horizontal gene transfer is unclear.
This project aims to investigate:
1.   Whether the exposure to non-antibiotic pharmaceuticals and personal care products can directly induce antibiotic resistance via mutagenesis.
2.   Could widely-used non-antibiotic pharmaceuticals and personal care products stimulate the horizontal transfer of antibiotic multi-resistance genes via conjugative gene transfer within and across bacterial genera.
3.   The effects of non-antibiotic pharmaceuticals and personal care products on the horizontal transfer of antibiotic multi-resistance genes via transformation.

Project Outcomes

We for the first time discovered that the pharmaceuticals and personal care products that we use daily are accelerating the spread of antibiotic resistance in environments.
More specifically, we found that:
1.   Antidepressant fluoxetine and toothpaste ingredient triclosan can induce mutations in Escherichia coli that convert mutant’s resistance against multiple antibiotics.
2.   Non-antibiotic pharmaceuticals carbamazepine and triclosan can significantly promote the conjugative transfer of antibiotic resistance genes within and across bacteria genera.
3.   Nonsteroidal anti-inflammatories, a lipid-lowering drug, a β-blocker and triclosan significantly promoted the uptake of antibiotic resistance genes via bacterial transformation.

Media releases

Our findings have been published in international scientific journals, which have attracted media coverage by more than 80 different press releases, including ABC News, The Daily Mail, Science Daily, The Courier-Mail and a television interview from 7 News channel.

Award

As a recognition of his achievements, Dr Lu has been awarded with the 2019 QLD Student Water Price by the Australian Water Association.

Publications

Lu, J., Jin, M., Nguyen, S.H., Mao, L., Li, J., Coin, L.J.M., Yuan, Z. & Guo, J., 2018. Non-antibiotic antimicrobial triclosan induces multiple antibiotic resistance through genetic mutation. Environ. Int. 118, 257-265.
Lu, J., Wang, Y., Li, J., Mao, L., Nguyen, S.H., Duarte, T., Coin, L., Bond, P., Yuan, Z. & Guo, J., 2018. Triclosan at environmentally relevant concentrations promotes horizontal transfer of multidrug resistance genes within and across bacterial genera. Environ. Int. 121, 1217-1226.
Lu, J., Wang, Y., Zhang, S., Bond, P. Yuan, Z. & Guo, J., 2020. Triclosan at environmental concentrations can enhance the spread of extracellular antibiotic resistance genes through transformation. Sci. Total Environ. 731, 136621.
Wang, Y., Lu, J., Mao, L., Li, J., Yuan, Z., Bond, P. L., & Guo, J. 2018. Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera. The ISME J. 13, 509-522.
Wang, Y., Lu, J., Engelstaedter, J., Zhang, S., Ding, P., Mao, L., Yuan, Z., Bond, P. L., & Guo, J. 2020. Non-antibiotic pharmaceuticals enhance the transmission of exogenous antibiotic resistance genes through bacterial transformation. The ISME J. 14, 2179–2196.
Jin, M., Lu, J., Chen, Z., Nguyen, S. H., Mao, L., Li, J., Yuan, Z., & Guo, J. 2018. Antidepressant fluoxetine induces multiple antibiotics resistance in Escherichia coli via ROS-mediated mutagenesis. Environ. Int. 120, 421-430.
Yu, Z., Wang, Y., Lu, J., Bond, PL. & J Guo. 2021. Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer. The ISME. 15, 2117-2130.
Yu, Z., Wang, Y., Henderson, IR. & J Guo. 2021. Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation. The ISME J.1-12.
Lu, J. & Guo, J. 2021. Disinfection spreads antimicrobial resistance. Science 371, 474.

Thesis

Lu, J. (2020). PhD thesis: Unravelling the roles of emerging environmental contaminants in promoting the spread of antibiotic resistance.
Wang, Y. (2021). PhD thesis: Unravelling roles of non-antibiotic pharmaceuticals on dissemination of antibiotic resistance in environmental settings