Bicyclomycin

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Bicyclomycin, discovered in 1972, has a structure that is unique among antibiotics. Currently used to treat nonspecific diarrhea, it has a low toxicity, and no cross-resistance with other antibiotics has yet been found. It is effective against many Gram-negative bacteria. Bicyclomycin is also effective against the Gram-positive bacterium Micrococcus luteus.[1] It is the only known selective inhibitor of Rho.


Mode of Action

Bicyclomycin inhibits Rho by being a reversible, noncompetitive inhibitor of ATP.[1]

Structure

Targets

Bicyclomycin targets the transcription termination factor Rho.[2]

Mechanisms of Resistance

Mutations that affect sensitivity

Genes in E. coli that affect sensitivity to bicyclomycin.[3]

Gene Allele Sensitivity to BCM Reference

recA

deletion

increased senstivity

PMID:21357484[3]

recO

deletion

increased sensitivity

PMID:21357484[3]

rdgC

deletion

increased sensitivity

PMID:21357484[3]

trxA

deletion

increased sensitivity

PMID:21357484[3]

trxB

deletion

increased sensitivity

PMID:21357484[3]

minC

deletion

increased sensitivity

PMID:21357484[3]

envC

deletion

increased sensitivity

PMID:21357484[3]

csgG

deletion

increased sensitivity

PMID:21357484[3]

pgpB

deletion

increased sensitivity

PMID:21357484[3]

yciB

deletion

increased sensitivity

PMID:21357484[3]

ydcS

deletion

increased sensitivity

PMID:21357484[3]

ydcX

deletion

increased sensitivity

PMID:21357484[3]




References

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  1. ↑ 1.0 1.1 Kohn, H & Widger, W (2005) The molecular basis for the mode of action of bicyclomycin. Curr Drug Targets Infect Disord 5 273-95 PubMed
  2. ↑ Zwiefka, A et al. (1993) Transcription termination factor rho: the site of bicyclomycin inhibition in Escherichia coli. Biochemistry 32 3564-70 PubMed
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 Tran, L et al. (2011) Single-gene deletion mutants of Escherichia coli with altered sensitivity to bicyclomycin, an inhibitor of transcription termination factor Rho. J. Bacteriol. 193 2229-35 PubMed