Antibiotics have made a massive contribution to human health by reducing the mortality and economic costs associated with bacterial disease. Unfortunately, antibiotic resistance in pathogenic bacteria threatens to undermine the clinical utility of antibiotics and we are currently faced with ominous possibility of a post-antibiotic era. Research in the MacLean lab is focused on understanding the fundamental evolutionary processes that drive the spread and maintenance of resistance, primarily using controlled in vitro experimental evolution in the opportunistic pathogenic bacterium Pseudomonas aeruginosa. The main themes that we work on are outlined below. Further information on our work and publications can be found on the MacLean group website (link to my group website)
Fitness costs and compensatory evolution
Antibiotic resistance usually reduces bacterial competitive ability, and this fitness cost is thought to represent a key obstacle to the spread of resistance at an epidemiological scale. We are interested in understanding why resistance carries a cost, and when this cost will cause resistance to decline after antibiotic use is reduced.
Evolutionary consequences of intervention strategies
How should we use antibiotics? This theme explores the evolutionary consequences of different intervention strategies, such as altering the frequency and intensity of antibiotic use, and how this impacts the dynamics of resistance at a population level.
Many of the most important antibiotic resistance genes in clinical pathogens are found on plasmids, autonomously replicating circles of DNA that can jump between bacteria. We are interested in understanding why resistance genes are on plasmids, and on how plasmids can persist in bacterial populations when antibiotic use declines.
Genomic drivers of resistance
Bacteria show extensive diversity in genome content and sequence. We are interested in understanding how genomic background shapes the rate and mechanisms of resistance evolution.