Dr. Siobhan O'Brien

Summary

Cystic fibrosis (CF) is an inherited chronic genetic disorder that negatively affects the respiratory and digestive system. The most common cause of mortality in CF is chronic lung infection with Pseudomonas aeruginosa (PA), a virulent pathogen that increases vulnerability to fatal secondary infections and is virtually impossible to eradicate once established. PA undergoes evolutionary changes as it adapts to life in the lung, leading to a diverse resident population of PA that are highly virulent and antibiotic-resistant. However, the drivers of PA evolution in the CF lung are not fully understood. Chronically colonized CF airways represent a surprisingly complex and diverse microbiota. Interactions between PA and other members of the lung microbiota can drive PA virulence and antibiotic resistance. However, our current understanding is largely limited to predictions based on simplified two-species environments in laboratory media. This project will begin to tackle the ambitious question of how multispecies interactions within complex CF lung communities drive the evolution of clinically-relevant changes in PA and vice versa.

Funding Agency

TCD Research Boost Award

Programme

Research Boost

Person Months

12

Summary

Funding Agency

IRC

Programme

New Foundations

Summary

Agricultural soil microbial communities provide vital ecosystem services such as providing nutrients to crops, protection against pathogens, breaking down toxic heavy metals and carbon storage. However, these communities are increasingly faced with harsh environmental conditions imposed by human activity - such as intensive use of pesticides, increased salinity from rising sea levels, and antibiotic run-off from pig farms. While experiments in vitro reveal that microbes can rapidly evolve resistance to such stressors, such studies are limited to a single species evolving in the presence of a single stressor in a highly artificial laboratory environment. In a complex natural community, however, evolutionary responses may be impeded because adapting to the presence of other competing species is more important than adapting to the environment. The ability of microbes to persist in the face of anthropogenic stress has clear consequences for maintaining ecosystem functions that rely on stable and efficient microbial communities. The proposed research will use real-time experimental evolution of soil microbial communities, to test if and how species interactions in complex soil microbial communities influence evolutionary responses to a stressful environment. We will focus on stressors highly relevant to agriculture: a broad-spectrum azole fungicide, antibiotic run-off from pig farms and increasing salinity and temperatures driven by climate change. Since environmental stressors are commonly encountered in combination, we will test the impact of these stressors individually and in combination. This research will yield insights into if and how evolutionary responses to agricultural stress occur in natural soil communities. Such questions are particularly relevant as we face challenges such as climate change and growing threats from agricultural pests, while simultaneously needing to feed over 9 billion people worldwide by 2050. This research will meet challenges associated with the BBSRC strategic priority 'Bioscience for sustainable agriculture and food', by gaining fundamental insights into the role of microbial evolutionary adaptation in an intense agricultural setting. Such fundamental understanding will inform future research that aims to harnass and manipulate microbial communties for efficient, environmentally friendly, food production. The need for fundamental, causal, microbiome research is highlighted by BBSRC prioritising Integrative Microbiome Research as a responsive mode priority in 2019.

Funding Agency

BBSRC

Summary

Antimicrobial resistance (AMR) is a pressing global issue that is expected to cause upwards of 10 million deaths a year by 2050. While responsible antibiotic stewardship has been advocated as crucial for controlling AMR, emerging evidence suggests that reducing antibiotic use alone may not be sufficient for curbing or reversing AMR. Anthropogenic activities, such as intensive agricultural practices, are now recognized as important and overlooked predictors of AMR evolution in natural bacterial populations. This can occur in three main ways: Firstly, antibiotics used in agriculture can discharge into soils, selecting for AMR bacteria in the natural environment. Secondly, agricultural stressors (e.g. pesticides and heavy metal waste) can select for resistance mechanisms in bacteria that inadvertently cause cross-resistance to antibiotics. Thirdly, agricultural stressors can "prime" soil bacteria for resistance to subsequent antibiotic influx, by generating the genetic variation required for subsequent selection to act on. Together, this suggests that agricultural chemicals can be key drivers of AMR, however we lack causative experiments that bridge the gap between simplified laboratory studies, and correlations based on natural soil communities. This project will examine how a commonly used fungicide (Fubol Gold), drives AMR evolution in the soil-dwelling opportunistic pathogen, Pseudomonas fluorescens.

Funding Agency

Trinity College Dublin Doctorate Award

Programme

Trinity College Dublin Doctorate Award

Summary

Cystic fibrosis (CF) is one of the most common recessively inherited rare diseases, affecting over 70000 people worldwide. The most common cause of mortality in CF is chronic lung infection with Pseudomonas aeruginosa - a virulent pathogen that is virtually impossible to eradicate once established. Successful treatment of P. aeruginosa infections is hampered by rapid evolutionary adaptation of P. aeruginosa within the lung, leading to diverse and unpredictable infections consisting of highvirulent subtypes. However, we do not yet understand the drivers of P. aeruginosa virulence evolution over the course of a chronic infection, making it difficult to predict the onset of exacerbated symptoms. This work will yield new insights into the drivers of clinically-important evolutionary changes in P. aeruginosa lung infections " so we will go from understanding what evolutionary changes occur to why they occur. It is now abundantly clear that P. aeruginosa is a pathogen that cannot be understood in isolation. Hence, successful treatment relies on predicting the dynamics of this pathogen in the context of the lung microbiota.

Funding Agency

IRC

Programme

Government of Ireland

Project Type

PhD Scholarship