Real-time measurements of aminoglycoside effects on protein synthesis in live cells

Aguirre Rivera, Javier,1989-Uppsala universitet,Molekylär systembiologi (author)

The spread of antibiotic resistance is turning many of the currently used antibiotics less effective against common infections. To address this public health challenge, it is critical to enhance our understanding of the mechanisms of action of these compounds. Aminoglycoside drugs bind the bacterial ribosome, and decades of results from in vitro biochemical and structural approaches suggest that these drugs disrupt protein synthesis by inhibiting the ribosome's translocation on the messenger RNA, as well as by inducing miscoding errors. So far, however, we have sparse information about the dynamic effects of these compounds on protein synthesis inside the cell. In the present study, we measured the effect of the aminoglycosides apramycin, gentamicin, and paromomycin on ongoing protein synthesis directly in live Escherichia coli cells by tracking the binding of dye-labeled transfer RNAs to ribosomes. Our results suggest that the drugs slow down translation elongation two- to fourfold in general, and the number of elongation cycles per initiation event seems to decrease to the same extent. Hence, our results imply that none of the drugs used in this study cause severe inhibition of translocation.

Larsson, Jimmy,1977-Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Molekylär systembiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)jilar813 (author)
Volkov, IvanUppsala universitet,Molekylär systembiologi(Swepub:uu)ivavo256 (author)
Seefeldt, A. CarolinUppsala universitet,Molekylär systembiologi(Swepub:uu)carse696 (author)
Sanyal, SuparnaUppsala universitet,Teknisk-naturvetenskapliga fakulteten,Molekylärbiologi(Swepub:uu)sucsa102 (author)
Johansson, MagnusUppsala universitet,Molekylär systembiologi(Swepub:uu)majoh087 (author)
Uppsala universitetMolekylär systembiologi (creator_code:org_t)

In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences (PNAS)118:90027-84241091-6490

By the author/editor: Aguirre Rivera, ...; Larsson, Jimmy, ...; Volkov, Ivan; Seefeldt, A. Car ...; Sanyal, Suparna; Johansson, Magnu ...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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