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bioRxiv · 10.1101/2024.01.08.574728

Deficiency in ribosome biogenesis causes streptomycin resistance and impairs motility in Salmonella

Lyu, Z.·Ling, Y.·Van Hoof, A.·Ling, J.
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Abstract

The ribosome is the central hub for protein synthesis and the target of many antibiotics. Whereas the majority of ribosome-targeting antibiotics inhibit protein synthesis and are bacteriostatic, aminoglycosides promote protein mistranslation and are bactericidal. Understanding the resistance mechanisms of bacteria against aminoglycosides is not only vital for improving the efficacy of this critically important group of antibiotics but also crucial for studying the molecular basis of translational fidelity. In this work, we analyzed Salmonella mutants evolved in the presence of the aminoglycoside streptomycin (Str) and identified a novel gene rimP to be involved in Str resistance. RimP is a ribosome assembly factor critical for the maturation of the 30S small subunit that binds Str. Deficiency in RimP increases resistance against Str and facilitates the development of even higher resistance. Deleting rimP decreases mistranslation and cellular uptake of Str, and further impairs flagellar motility. Our work thus highlights a previously unknown mechanism of aminoglycoside resistance via defective ribosome assembly.

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Lyu, Z., Ling, Y., Van Hoof, A., Ling, J.. 2024-01-09. Deficiency in ribosome biogenesis causes streptomycin resistance and impairs motility in Salmonella. https://doi.org/10.1101/2024.01.08.574728

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