Antibiotics
Cyclic di-GMP Regulation of Antibiotic-Induced Biofilm Formation: A Systematic Review
By Karim ME, Eubank T, Begum K and 3 others.
Abstract
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.
Methods
A systematic literature search was conducted in PubMed and Scopus for articles published from inception to 18 December 2025 using terms including "sub-MIC antibiotic" AND ("biofilm" OR "antibiotic-induced biofilm") and a second search using "sub-MIC antibiotic" AND "biofilm" AND "c-di-GMP". Reviews, commentaries, opinions, meta-analyses, systematic reviews, and non-English-language articles were excluded.