Antibiotics are vital to treat and prevent infection, although the increasing multidrug resistance demands new antibiotic development or maintain the efficacy of available antibiotics. The resistance phenomenon is driven by different resistance methods such as ribosome modification and antibiotic sequestration. ABC Subfamily F (ABCF) proteins are cytosolic ribosome-binding ATPases that regulate translation or confer antibiotic resistance to all clinically important groups of antibiotics that bind the large ribosomal subunit (the 50S) through a ribosome protection mechanism. Recently, our group discovered that ABCF protein LmrC transduces the lincomycin synthesis in reaction to functionally related antibiotics, although previously LmrC was classified as pure antibiotic resistance (ARE). We hypothesize that analogous ABCF-mediated antibiotic signaling may function in selective gene expression in response to small molecules targeting the 50S ribosomal subunit, including clinically important antibiotics, to mediate intercellular antibiotic signaling or even induction of a stress response. To prove the hypothesis, we will imply biochemical, biophysical, and molecular biology in vitro approaches to unravel the molecular mechanism of ABCF protein-mediated antibiotic signaling and investigate the potential of ABCF proteins to regulate gene expression in response to antibiotics in actinomycetes. How does the LmrC interact with ribosomes and what are crucial domains for interaction will be studied by structural techniques such as X-Ray and Cryo-EM.