Hyperpiliation, not loss of pilus retraction, reduces Pseudomonas aeruginosa pathogenicity

• DOI: 10.1128/spectrum.02558-24
• Publication Date: 2025-02-25T14:09:33Z
• Authors: Sara L. N. Kilmury; Katherine J. Graham; Ryan P. Lamers; Lesley T. MacNeil; Lori L. Burrows
• Keywords: Pilin; Pathogenicity island

ABSTRACT Type IVa pili (T4aP) are important virulence factors for many bacterial pathogens. Previous studies suggested that the retraction ATPase, PilT, modulates pathogenicity due to its critical role in pilus dynamics and twitching motility. Here we use a Caenorhabditis elegans slow-killing model show hyperpiliation, not loss of retraction, reduces Pseudomonas aeruginosa strains PAK PA14. Hyperactivating point mutations P. PilSR two-component system controls transcription major pilin gene, pilA , increased levels surface same extent as deleting pilT without impairing These functionally hyperpiliated mutants had significant defects were rescued by or through disruption hyperpiliation via deletion type III secretion needle-length regulator, PscP. Hyperpiliated pilO showed similar PilA-dependent impairments virulence, validating phenotype. Together, our data support where surfeit potentially prevention effective engagement contact-dependent factors. findings suggest T4aP should be revised. IMPORTANCE is contributor hospital-acquired infections particularly problematic intrinsic resistance front-line antibiotics. Strategies combat this other pathogens include development anti-virulence therapeutics. We impaired when amount expressed on cell increases, independent bacteria’s ability twitch. propose having excess may physically interfere with productive toxin delivery system. A better understanding how modulate interaction bacteria target cells will improve design therapeutics targeting components involved regulation expression function reduce clinical burden T4aP-expressing bacteria.