The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.

Tan, Cheemeng

Smith, Robert Phillip

Srimani, Jaydeep K

Riccione, Katherine A

Prasada, Sameer

Kuehn, Meta

You, Lingchong

England

2015-10-05T18:43:25Z

2012

The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to 'band-pass' response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes.

http://www.ncbi.nlm.nih.gov/pubmed/23047527

msb201249

1744-4292

https://hdl.handle.net/10161/10659

eng

EMBO

Mol Syst Biol

10.1038/msb.2012.49

Anti-Bacterial Agents

Bacteria

Chloramphenicol

Colony Count, Microbial

Escherichia coli

Heat-Shock Response

Kanamycin

Kinetics

Microbial Sensitivity Tests

Models, Biological

Proteolysis

Ribosomes

Salmonella typhimurium

The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.

Journal article

Kuehn, Meta|0000-0003-0519-3019

http://www.ncbi.nlm.nih.gov/pubmed/23047527

617

Basic Science Departments

Biochemistry

Biomedical Engineering

Duke

Duke Cancer Institute

Institutes and Centers

Molecular Genetics and Microbiology

Pratt School of Engineering

School of Medicine

Published

8