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Beyond Self-Resistance: ABCF ATPase LmrC Is a Signal-Transducing Component of an Antibiotic-Driven Signaling Cascade Accelerating the Onset of Lincomycin Biosynthesis
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SYSNO ASEP 0551070 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Beyond Self-Resistance: ABCF ATPase LmrC Is a Signal-Transducing Component of an Antibiotic-Driven Signaling Cascade Accelerating the Onset of Lincomycin Biosynthesis Tvůrce(i) Koběrská, Markéta (MBU-M) ORCID
Veselá, Ludmila (MBU-M)
Vimberg, Vladimír (MBU-M) ORCID
Lenart, Jakub (MBU-M) RID
Veselá, Jana (MBU-M)
Kameník, Zdeněk (MBU-M) RID, ORCID
Janata, Jiří (MBU-M) RID, ORCID
Balíková Novotná, Gabriela (MBU-M) ORCIDČíslo článku e01731-21 Zdroj.dok. mBio. - : American Society for Microbiology - ISSN 2161-2129
Roč. 12, č. 5 (2021)Poč.str. 20 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova ABCF ATPase ; Antibiotic biosynthesis ; Antibiotic resistance ; Antibiotic-mediated signaling ; Chemical communication ; Regulation of gene expression ; Ribosomal regulation ; Signal transduction ; Specialized metabolism ; Streptomyces Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology CEP GJ15-16225Y GA ČR - Grantová agentura ČR GPP302/12/P632 GA ČR - Grantová agentura ČR ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 UT WOS 000738772600010 EID SCOPUS 85121015230 DOI 10.1128/mBio.01731-21 Anotace In natural environments, antibiotics are important means of interspecies competition. At subinhibitory concentrations, they act as cues or signals inducing antibiotic production, however, our knowledge of well-documented antibiotic-based sensing systems is limited. Here, for the soil actinobacterium Streptomyces lincolnensis, we describe a fundamentally new ribosome-mediated signaling cascade that accelerates the onset of lincomycin production in response to an external ribosome-targeting antibiotic to synchronize antibiotic production within the population. The entire cascade is encoded in the lincomycin biosynthetic gene cluster (BGC) and consists of three lincomycin resistance proteins in addition to the transcriptional regulator LmbU: a lincomycin transporter (LmrA), a 23S rRNA methyltransferase (LmrB), both of which confer high resistance, and an ATP-binding cassette family F (ABCF) ATPase, LmrC, which confers only moderate resistance but is essential for antibiotic-induced signal transduction. Specifically, antibiotic sensing occurs via ribosome-mediated attenuation, which activates LmrC production in response to lincosamide, streptogramin A, or pleuromutilin antibiotics. Then, ATPase activity of the ribosome-associated LmrC triggers the transcription of lmbU and consequently the expression of lincomycin BGC. Finally, the production of LmrC is downregulated by LmrA and LmrB, which reduces the amount of ribosome-bound antibiotic and thus fine-tunes the cascade. We propose that analogous ABCF-mediated signaling systems are relatively common because many ribosome-targeting antibiotic BGCs encode an ABCF protein accompanied by additional resistance protein(s) and transcriptional regulators. Moreover, we revealed that three of the eight coproduced ABCF proteins of S. lincolnensis are clindamycin responsive, suggesting that the ABCF-mediated antibiotic signaling may be a widely utilized tool for chemical communication. IMPORTANCE Resistance proteins are perceived as mechanisms protecting bacteria from the inhibitory effect of their produced antibiotics or antibiotics from competitors. Here, we report that antibiotic resistance proteins regulate lincomycin biosynthesis in response to subinhibitory concentrations of antibiotics. In particular, weF show the dual character of the ABCF ATPase LmrC, which confers antibiotic resistance and simultaneously transduces a signal from ribosome-bound antibiotics to gene expression, where the 59 untranslated sequence upstream of its encoding gene functions as a primary antibiotic sensor. ABCF-mediated antibiotic signaling can in principle function not only in the induction of antibiotic biosynthesis but also in selective gene expression in response to any small molecules targeting the 50S ribosomal subunit, including clinically important antibiotics, to mediate intercellular antibiotic signaling and stress response induction. Moreover, the resistance-regulatory function of LmrC presented here for the first time unifies functionally inconsistent ABCF family members involving antibiotic resistance proteins and translational regulators. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2022 Elektronická adresa https://journals.asm.org/doi/10.1128/mBio.01731-21
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