Macquarie University research sheds light on how antibiotic resistance can be better managed

6 July 2017

By recreating the origins of DNA elements that confer antibiotic resistance, researchers from Macquarie University generate new insights that can help limit resistance in the future

  • The key element (the class 1 integron) is a major player in the global dissemination of antibiotic resistance, and is now found in every human gut and every ecosystem.
  • New Macquarie University research – recently published in PLOS ONE – recreated the single event that formed these class 1 integrons, 100 years ago.
  • The findings call for better waste management of antibiotics, and surveillance of antibiotic resistance to limit the impact of the current antibiotic resistance epidemic.

By recreating the evolutionary history of class 1 integrons – a class of DNA element widely known to be a major player in the global rise of antibiotic resistance – Macquarie University researchers have, for the first time, identified how the element entered the human food chain, and how our activities have led to the element’s spectacular rise in distribution.

This origin of this integron is likely to have occurred inside a bacterial cell living on the surface of plants, and happened as recently as 100 years ago. Driven by human activity, the class 1 integron has now invaded a diverse range of bacterial and animal hosts, spreading to over 70 bacterial species of medical importance. It has invaded every continent on earth, including Antarctica.

Importantly, these findings provide insights to help limit the current crisis in antibiotic resistance.

“By mapping the introduction and spread of antibiotic resistance, we hope to slow the spread of resistance, by modifying how humans use and dispose of antibiotics,” Professor Michael Gillings notes.

“Since the class 1 integron has played such an important role in the global spread of multi-drug resistance, it is important to reconstruct its evolutionary history so that we can better manage antibiotic resistance, and gain insights into how human activities influence bacterial evolution,” said co-author of the study Professor Michael Gillings, of Macquarie University.

The study examined the most likely route for the movement of class 1 integrons from natural environments into the human microbiota (i.e. gut bacteria), by examining various foods, including leafy vegetables, for their potential carriage of integron-bearing bacteria.

“We found these integrons in a particular bacterial strain isolated from baby spinach leaves, which provides a plausible route for transmission of environmental integrons into the human microbiota,” Professor Gillings continued.

Once resident in the microbiota, the possession of genes known to confer resistance to arsenic, mercury and disinfectants supplied both the integron and its bacterial host with a means of preferential survival, since all these agents of selection were in use well before the antibiotic era, the study found.

Antibiotic resistance is a growing problem worldwide, and Professor Gillings explains that the primary cause of the spread may be human misuse of antibiotics. This eventually leads to integrons being able to pollute our food supplies and colonize wild and domesticated animals.

“When humans or animals consume antibiotics, 70 per cent of that drug can be excreted as waste. Our waste management system isn’t able to filter out the metals, disinfectants or antibiotic agents. This waste helps select and maintain antibiotic resistant bacteria in the environment,” says Professor Gillings. “Consequently the class 1 integron now pollutes all human-dominated ecosystems.”

The research findings call for more advanced monitoring and surveillance of the way these resistance genes travel, as well as calling for a set of standards for the release of metals, disinfectants, antibiotics and other agents into the environment (especially via human waste).

Professor Gillings concludes that understanding the evolution and dispersal of resistance is critical to predicting and controlling the spread.

“Class 1 integrons now exist in every human gut and ecosystem and contain more than 130 antibiotic resistance genes. Understanding the types of resistance genes in each integron and how they spread is the only way modern medicine can hope to compete with the rapid spread of resistance.”

The PLOS ONE research paper can be found at the following link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179169.

Some of Professor Gillings’ recent research – published in the Current Opinion in Microbiology journal – on the role of integrons in antibiotic resistance can be found here: http://www.sciencedirect.com/science/article/pii/S1369527416301709.

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