UNLABELLED: ABCF-ATPases are increasingly recognized as translation factors that rescue stalled ribosomes when they encounter difficult mRNA templates or are stalled by antibiotics. The latter defines antibiotic resistance ABCF (ARE ABCF) proteins, known for their role in antibiotic resistance. However, in this study, we reveal a broader role of ARE ABCFs in antibiotic-responsive regulation. Using genetic, OMICs, and biochemical approaches, we showed that ARE ABCF proteins TiaA and Are5sc in Streptomyces coelicolor use their resistance functions to modulate specialized metabolism and proteosynthesis in response to lincosamide, streptogramin A, and pleuromutilin (LSAP) antibiotics. Although under LSAP exposure, either Are5sc or TiaA is essential for activating the biosynthesis of the redox-active antimicrobial actinorhodin, these proteins exhibit distinct functions at the proteome level, defined by their resistance profiles and temporally regulated expression. Are5sc facilitates early adaptive responses by modulating the WblC regulon across a broad range of LSAP concentrations, while TiaA is induced later, specifically at higher concentrations, where it suppresses antibiotic stress responses, particularly against pleuromutilins. TiaA function thus reflects the ecological context of LSAP antibiotics as pleuromutilins are produced by fungi, whereas lincosamides/streptogramins originate from actinomycetes. Our findings demonstrate that ARE ABCF proteins, through their resistance function, act as global regulators of translation, mirroring the roles of non-ARE ABCF proteins like EttA. This highlights their broader ecological and physiological significance, extending beyond their established role in antibiotic resistance. IMPORTANCE: Bacteria adapt to diverse stimuli mainly through transcriptional changes that regulate adaptive protein factors. Here, we show that responses to protein synthesis-inhibiting antibiotics are fine-tuned by antibiotic resistance ABCF proteins at the translational level, enabling bacteria to differentiate between antibiotic classes and concentrations for a tailored response. Additionally, we have demonstrated that these proteins can specialize in conferring high-level resistance to specific antibiotics. Given their prevalence in pathogenic bacteria, antibiotic resistance ABCF (ARE ABCF) proteins may play a crucial role in resistance development, particularly against new antibiotics targeting the ribosomal catalytic center, presenting a significant challenge for antimicrobial therapy.

• Klíčová slova
• ABCF proteins, Streptomyces, antibiotic resistance, stress adaptation, stress response, translational control,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• bakteriální léková rezistence * MeSH
• bakteriální proteiny * genetika   metabolismus   MeSH
• diterpeny farmakologie   MeSH
• linkosamidy farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• pleuromutiliny MeSH
• polycyklické sloučeniny farmakologie   MeSH
• proteosyntéza MeSH
• regulace genové exprese u bakterií účinky léků   MeSH
• Streptomyces coelicolor * účinky léků   genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• bakteriální proteiny * MeSH
• diterpeny MeSH
• linkosamidy MeSH
• pleuromutiliny MeSH
• polycyklické sloučeniny MeSH