Pseudomonas aeruginosa is able to tolerate exposure to high concentrations of beta-lactam antibiotics. We have found that when treated with beta-lactams, P. aeruginosa undergoes a rapid en masse transition from bacillary cells to viable, cell wall defective spherical cells1 . Interestingly, we found that upon antibiotic removal, the entire population of spherical cells quickly converts back to bacillary cells1 . Our results suggest that these rapid and reversible population-wide morphotype transitions function as a strategy to survive exposure to beta-lactam antibiotics. We have found that P. aeruginosa can be efficiently killed by inducing en masse transition to the spherical cell morphotype and then exploiting the relative fragility and sensitivity of these cells to killing by antimicrobial peptides (AMPs) to which the bacillary morphotype is resistant1 . We have recently completed a genome-wide survey of a P. aeruginosa transposon mutant library to identify genes involved in transitions between bacillary and spherical cell morphotypes and spherical cell survival.
Interestingly, the formation of spherical cells by P. aeruginosa in response to beta-lactams is remarkably similar to the process described for the production of cell wall defective bacterial variants termed L-forms. We are currently exploring the possibility that the beta-lactam induced spherical cell morphotypes of P. aeruginosa are indeed L-forms and have found that with extended beta-lactam exposure, the spherical cell morphotype of P. aeruginosa proliferates via a process which is highly similar to that described for L-form proliferation.
Our studies suggest that the ability to rapidly and reversibly transition between bacillary cells and L-forms serves as a survival mechanism that enables the bacterial population to tolerate the presence of cell wall inhibitors. We suggest that this may be a bona fide biological role for bacterial L-forms. Importantly our observations indicate that novel antibiotic therapies can be developed that act by inducing and killing bacterial L-forms.