How ecology can affect antibiotic resistance

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The Microbiology Society is undertaking a project entitled A Sustainable Future as part of our 75th Anniversary, which aims to highlight the Sustainable Development Goals (SDGs) to our members and empower them to use their research to evidence and impact the goals. Earlier this year, we put a call out to our members to submit case studies in the following three areas: antimicrobial resistance, soil health and the circular economy.

This case study is written by Dr Michael Bottery, who is a Centre for Future Health Research Fellow at the University of York and a member of the Microbiology Society. It focuses on antimicrobial resistance; a naturally occurring process, whereby micro-organisms (bacteria, viruses, fungi and parasites) can change and adapt over time, either by modifying the target of the antimicrobial, or by developing and exchanging resistance genes.

Introduction to the project

Bacteria have social lives—they are able to signal with each other to coordinate communal activities, such as foraging for rare resources, conducting chemical warfare, producing virulence factors, and forming highly resilient biofilms. These social traits are critical for many bacteria to grow in harsh environments, such as those within our bodies, and provide some species with the ability to cause infection.

What are the challenges/needs that this research/initiative addresses?

Many of these social interactions are intended for cooperation between members of the same species or strain but the benefits of some cooperative traits are leaky and can be exploited by different species within the bacterial community. This is of particular concern when the cooperative traits in question provide increased tolerance to antibiotics. The presence of a resistant bacterial species, which may not be of clinical concern or the target of antibiotic treatment, may increase the tolerance of the true pathogens within the community.

Cystic Fibrosis (CF) is a genetic condition that leads to the build-up of thick, sticky mucus within the lungs, making the lungs prone to polymicrobial infections that consist of multiple different species of bacteria. However, specific species are of particular concern, such as Pseudomonas aeruginosa, which is the leading cause of morbidity and mortality in CF patients. Upon the detection of P. aeruginosa within the airways, antibiotic eradication therapy is conducted with the aim of clearing the pathogen from the lungs. However, susceptibility of P. aeruginosa to antibiotics within the lab is often a poor indicator of the success of the antibiotic within the patient.

What findings and solutions were provided by this research/initiative?

Using model CF lung communities in the lab, we are investigating whether P. aeruginosa can exploit the innate antibiotic resistance of other bacteria that commonly co-infect the CF lung. Co-infections with the bacterium Stenotrophomonas maltophilia are increasing in prevalence but the clinical importance of this bacterium is unclear and it is not commonly a target of antibiotic treatment. However, S. maltophilia innately inactivates many anti-pseudomonal antibiotics, including carbapenems, through the release of beta-lactamase enzymes. This cooperative trait can be socially exploited by P. aeruginosa in the lab, with co-cultures of the two strains providing high levels of protection to P. aeruginosa. Confounding this problem, inhibitors designed to block the action of the beta-lactamase enzymes that are commonly used together with these antibiotics do not work against S. maltophilia enzymes and do not alter the efficacy of the antibiotics. In contrast, the presence of Staphylococcus aureus, another commonly co-occurring CF pathogen, provides P. aeruginosa with no protection, but instead, makes P. aeruginosa more susceptible to some antibiotics due to intensified competition.

These findings reveal that social exploitation of pre-occurring antimicrobial resistance, and inter-specific competition, can have a large effect on the efficacy of antibiotic treatments, highlighting the importance of microbial ecology for understanding antibiotic resistance particularly during polymicrobial infections.

© Michael Bottery
About the author

Dr Michael Bottery is a Centre for Future Health Research Fellow at the University of York and a member of the Microbiology Society. More information about his work is available here.