A Numbers Game: Ribosome Densities, Bacterial Growth, and Antibiotic-Mediated Stasis and Death

MBio
Bruce R LevinFernando Baquero

Abstract

We postulate that the inhibition of growth and low rates of mortality of bacteria exposed to ribosome-binding antibiotics deemed bacteriostatic can be attributed almost uniquely to these drugs reducing the number of ribosomes contributing to protein synthesis, i.e., the number of effective ribosomes. We tested this hypothesis with Escherichia coli K-12 MG1655 and constructs that had been deleted for 1 to 6 of the 7 rRNA (rrn) operons. In the absence of antibiotics, constructs with fewer rrn operons have lower maximum growth rates and longer lag phases than those with more ribosomal operons. In the presence of the ribosome-binding "bacteriostatic" antibiotics tetracycline, chloramphenicol, and azithromycin, E. coli strains with 1 and 2 rrn operons are killed at a substantially higher rate than those with more rrn operons. This increase in the susceptibility of E. coli with fewer rrn operons to killing by ribosome-targeting bacteriostatic antibiotics is not reflected in their greater sensitivity to killing by the bactericidal antibiotic ciprofloxacin, which does not target ribosomes, but also to killing by gentamicin, which does. Finally, when such strains are exposed to these ribosome-targeting bacteriostatic antibiotics, the ti...Continue Reading

Citations

Nov 15, 2017·FEMS Microbiology Reviews·Fernando Baquero
Dec 1, 2017·MBio·Fernando Baquero, José-Luis Martínez
Dec 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·Maxim S SvetlovAlexander S Mankin
Oct 8, 2020·Nature Reviews. Microbiology·Fernando Baquero, Bruce R Levin
Feb 13, 2021·Proceedings of the National Academy of Sciences of the United States of America·Markus HuemerAnnelies S Zinkernagel
Oct 20, 2017·Current Opinion in Microbiology·Jason H YangJames J Collins
Mar 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Brandon A BerryhillBruce R Levin
May 26, 2020·Trends in Biochemical Sciences·Xiongfeng Dai, Manlu Zhu

Datasets Mentioned

BETA
MG1655

Methods Mentioned

BETA
RNA assay
Bioscreen
nuclear magnetic resonance

Related Concepts

Bacteriocidal Agents
Ribosomes
Protein Biosynthesis
Escherichia coli K12
Virus Viability
Antibiotics
Antineoplastic Agents
Bactericide, NOS
Chloramphenicol
Escherichia coli

Related Feeds

Campylobacteriosis (ASM)

Campylobacteriosis is caused by the bacteria Campylobacter jejuni and is a common cause of gastroenteritis in humans. Discover the latest research on Campylobacteriosis here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.