Entropically driven aggregation of bacteria by host polymers promotes antibiotic tolerance in Pseudomonas aeruginosa

Significance Bacteria live in aggregates at sites of chronic infection, and aggregated growth is thought to be important in producing key infection phenotypes such as antibiotic tolerance. We found that entropic forces generated by polymers abundant at chronic infection sites can cause bacteria to aggregate by a mechanism known as “depletion aggregation.” This aggregation mechanism does not require biofilm formation functions, but it does cause bacteria to become much less susceptible to killing by antibiotics. These findings indicate that aggregation could be a default growth mode at infection sites. It might be useful to target mechanisms of depletion-mediated antibiotic tolerance for the treatment of chronic infections.