Imipenem-induced outer membrane vesicles from Elizabethkingia anophelis inhibit biofilm formation and shift nosocomial pathogen dynamics

Abstract

Elizabethkingia anophelis is an emerging multidrug-resistant Gram-negative pathogen that can cause severe nosocomial infections. Although multidrug resistance complicates the clinical management of E. anophelis, the ecological impact of stress responses, including antibiotic pressure, is unclear. We demonstrated that exposure to sub-inhibitory concentrations of imipenem promoted the secretion of antibiotic-induced outer membrane vesicles (iOMVs) by E. anophelis. This study analyzed the physical and functional characteristics of iOMVs produced by a drug-resistant clinical isolate of E. anophelis treated with imipenem and assessed the potential of E. anophelis iOMVs to modulate biofilm formation in other clinically relevant Gram-negative bacteria. High-resolution imaging and biofilm assays showed that iOMVs inhibited biofilm formation and reduced biofilm density. The inhibitory effect did not affect other nosocomial pathogens such as Pseudomonas aeruginosa, Enterobacter cloacae, or Klebsiella pneumoniae. Imipenem-induced vesiculation may inadvertently impair E. anophelis’ biofilm resilience while altering microbial competition, reshaping survival dynamics in polymicrobial environments. These results demonstrate the paradoxical effect of antibiotic stress and suggest that vesicle-mediated interactions strongly affect nosocomial pathogen ecology.