Active Infection & Immunity Lungs & Breathing

Elucidating the intra-macrophage lifestyle of Pseudomonas aeruginosa and its impacts on the evolution of antibiotic resistance and tolerance.

Funder Wellcome Charity-funded
Recipient organisation University of Edinburgh
Funding Not disclosed
Period Oct 2025 — Sept 2028

In plain English

AI plain-English summary

*Pseudomonas aeruginosa* bacteria are invading the very immune cells meant to destroy them—macrophages—and hiding inside to survive antibiotic attacks. This matters because *P. aeruginosa* causes chronic, drug-resistant lung infections in people with cystic fibrosis, and current treatments often fail. Scientists have long assumed these bacteria operate only outside host cells. This project challenges that assumption by investigating what happens when bacteria live *inside* macrophages, the immune system’s first responders. The researchers will build a mathematical model of bacterial dynamics inside macrophages, then use microscopy and molecular tools to watch the infection unfold in real time. They will then evolve the bacteria inside macrophages while exposing them to antibiotics, tracking how resistance and tolerance emerge over generations. If successful, this work will reveal the molecular tricks *P. aeruginosa* uses to survive intracellularly and map the evolutionary pathways that lead to antibiotic failure. The immediate impact is fundamental: it redefines how we think about a major pathogen’s lifestyle. In the longer term, understanding these hidden survival strategies could guide the design of drugs that flush bacteria out of macrophages or block their entry—potentially shifting treatment for cystic fibrosis and other chronic infections.

View original technical description
Pseudomonas aeruginosa is a significant cause of chronic antibiotic recalcitrant infections in Cystic Fibrosis patients worldwide. This is due to a wide range of factors including metabolic flexibility, secreted virulence effectors and extensive intrinsic antibiotic resistance. Whilst classically considered to act extracellularly, recent studies have begun to elucidate its entry and residence within macrophages, cells key to innate immunity. The drivers of this lifestyle and its potential consequences on pathogenicity and antibiotic resistance traits, are, however, yet to be elucidated. This project proposes, therefore, to characterise intracellular P. aeruginosa infection and investigate the evolution of resistance and tolerance traits within macrophages over time. This will be achieved by first developing a mathematical framework modelling bacterial dynamics to guide and inform experimental approaches. Microscopy and molecular techniques will be utilised and compared to set up an appropriate experimental model, characterise intra- macrophage infection and quantify model parameters. Finally, experimental evolution of P. aeruginosa within macrophages in the presence of antibiotic will be conducted to assess changes in resistance profiles, phenotype and virulence. This project will define the molecular mechanisms by which P. aeruginosa survives and persists intracellularly, alongside elucidating evolutionary pathways that emerge within macrophages as a result of prolonged antibiotic exposure

View the original record at the funder ↗

Researchers

Iris Floria (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Determining the architecture of antibiotic resistance evolvability
Investigating Pseudomonas aeruginosa physiology and the impact of pathoadaptive mutations, in a polymicrobial airway environment
Evolutionary responses of microbiomes during therapeutic interventions
Antimicrobial resistance mechanisms in the presence of sub-inhibitory antibiotics and the microbiome
Developing novel antimicrobial macrocycles against multidrug resistant bacteria that cause chronic lung infections

Original classification

PhD Studentship (Basic)

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.