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ABSTRACT: Study on antibiotic resistance genes in soil environments of wetland

PROVIDER: PRJNA944845 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23867569_1.fastq.gz	Fastqsanger.gz
	SRR23867569_2.fastq.gz	Fastqsanger.gz
	SRR23867570_1.fastq.gz	Fastqsanger.gz
	SRR23867570_2.fastq.gz	Fastqsanger.gz
	SRR23867571_1.fastq.gz	Fastqsanger.gz

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Beyond self-resistance: ABCF ATPase LmrC is a signal-transducing component of an antibiotic-driven signaling cascade hastening the onset of lincomycin biosynthesis

Project description:In natural environments, antibiotics are an important instrument of inter-species 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 the antibiotic production within the population. The entire cascade is encoded within the lincomycin biosynthetic gene cluster (BGC) and besides the transcriptional regulator, LmbU it consists of three lincomycin resistance proteins: a lincomycin transporter, LmrA, a 23S rRNA methyltransferase, LmrB, both conferring a high resistance, and an ABCF ATPase LmrC that confers only moderate resistance but is indispensable for the antibiotic-induced signal transduction. Specifically, the antibiotic sensing occurs via a ribosome-mediated attenuation, which activates LmrC production in response to lincosamide, streptogramin A, or pleuromutilin antibiotics. Then, the ribosome-operating LmrC ATPase activity 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 the ribosome-bound antibiotic and thus fine-tune the cascade. We propose that analogous ABCF-mediated signaling systems are relatively common because many BGCs for ribosome-targeting antibiotics encode an ABCF-protein accompanied by additional resistance protein(s) and transcriptional regulators. Moreover, we revealed that three of eight co-produced ABCF proteins of S. lincolnensis are clindamycin-responsive thus the ABCF-mediated antibiotic signaling might be generally utilized tool of chemical communication.

2021-08-18 | PXD026093 | Pride

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