Retrieving of diguanylate cyclases responsible for biofilm formation and antibiotic resistance in Acinetobacter baumannii.

BACKGROUND: As a common opportunistic nosocomial pathogen, Acinetobacter baumannii has emerged as an increasingly multidrug-resistant threat due to its strong biofilm lifestyle. The GGDEF/EAL domain proteins regulate c-di-GMP metabolism, thereby affecting biofilm formation and antibiotic resistance. Nevertheless, the effects of such proteins on biofilm formation and antibiotic resistance of A. baumannii remain unclear. RESULTS: In this study, we identified and characterized the GGDEF/EAL domain proteins in A. baumannii and evaluated their contributions to biofilm formation and antibiotic resistance. Comparative genomic analysis revealed eleven genes encoding putative proteins that metabolize c-di-GMP in A. baumannii EMB-1. Overexpression of individual putative proteins showed that a diguanylate cyclase DGC8 markedly influenced the colony morphology, surface-associated motility, and biofilm formation of A. baumannii EMB-1. Furthermore, the antibiotic susceptibility test showed that DGC8 enhances the resistance of EMB-1 to four frequently used antibiotics (i.e., ceftazidime, cefepime, levofloxacin, and tigecycline). Importantly, molecular biology evidence suggests that DGC8 regulates biofilm formation through the Csu pili-mediated pathway. CONCLUSIONS: Together, our findings provide a basis for understanding the physiology of drug resistance in A. baumannii through the regulation of biofilm formation and surface-associated motility, shedding light on targeting DGC8 as an emerging mitigation strategy to control this pathogen.