Cyclic di-GMP Regulation of Antibiotic-Induced Biofilm Formation: A Systematic Review

Background/Objectives: Biofilm formation is a major bacterial survival strategy in response to antibiotic stress. The bacterial second messenger cyclic di-GMP (c-di-GMP) is a central regulator of biofilm development. Sub-minimum inhibitory concentrations (sub-MICs) of antibiotics act as biological active environmental cues that reprogram bacterial physiology and promote biofilm development. This systematic review synthesizes the current literature on sub-MIC antibiotic-induced biofilm formation across different pathogenic bacterial genera and critically evaluates the role of c-di-GMP.