Crawling in the dark? How Pseudomonas aeruginosa navigates antibiotic gradients in biofilms

Year of award: 2024

Grantholders

  • Dr James Wheeler

    University of Liverpool, United Kingdom

Project summary

Pseudomonas aeruginosa is a globally significant “priority” bacterial pathogen (WHO) that causes biofilm-associated, antibiotic-resistant infections. Bacteria like P. aeruginosa have often been studied in liquid-culture, a lifestyle that does not reflect the surface-attached biofilms associated with natural and clinical environments. Decades of chemotaxis research have characterised how liquid-borne bacteria swim towards nutrients and avoid harm by detecting temporal changes in chemical concentration. However, swimming is ineffective in biofilms; P.aeruginosa instead crawls across surfaces via twitching motility. Unlike swimming bacteria, I have found that twitching cells sense spatial differences in concentration across their cell bodies and that, counter-intuitively, they move towards harmful antibiotics (antibiotic taxis). These exciting discoveries lead me to ask how bacteria could measure gradients at the micron-level, and why P.aeruginosa moves towards antibiotics. Furthermore, twitching chemotaxis has only been studied in isolated cells and we know little about how cells navigate within biofilms, how antibiotic taxis influences resistance acquisition, or how twitching chemotaxis influences host infection and antibiotic treatment. Here, I ask: - How do bacteria measure concentration in space? - How do twitching cells navigate within biofilms? - How does antibiotic taxis impact antibiotic resistance? - How does twitching chemotaxis influence host infection and antibiotic therapy?