2005
DOI: 10.2174/1568005054880136
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The Molecular Basis for the Mode of Action of Bicyclomycin

Abstract: Bicyclomycin (1) is a clinically useful antibiotic exhibiting activity against a broad spectrum of Gram-negative bacteria and against the Gram-positive bacterium, Micrococcus luteus. Bicyclomycin has been used to treat diarrhea in humans and bacterial diarrhea in calves and pigs and is marketed by Fujisawa (Osaka, Japan) under the trade name Bicozamycin. The structure of 1 is unique among antibiotics, and our studies document that its mechanism of action is novel. Early mechanistic proposals suggested that 1 r… Show more

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Cited by 73 publications
(70 citation statements)
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References 104 publications
(413 reference statements)
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“…Several antimicrobial resistance genes were found in the BAA-410 genome (see Table S4 in the supplemental material). These include the TetH tetracycline resistance protein (MHA_1158) and its regulator TetR (MHA_1159), a possible Zn-␤-lactamase (MHA_2752), and a major facilitator superfamily permease possibly associated with efflux of bicyclomycin (MHA_1575), an antibiotic that targets transcription terminator factor (38). Orthologs of the resistance-nodulation-cell division superfamily multidrug efflux pump AcrAB, as well as the regulatory protein AcrR (MHA_0370 to MHA_0372), are also present (41).…”
Section: Resultsmentioning
confidence: 99%
“…Several antimicrobial resistance genes were found in the BAA-410 genome (see Table S4 in the supplemental material). These include the TetH tetracycline resistance protein (MHA_1158) and its regulator TetR (MHA_1159), a possible Zn-␤-lactamase (MHA_2752), and a major facilitator superfamily permease possibly associated with efflux of bicyclomycin (MHA_1575), an antibiotic that targets transcription terminator factor (38). Orthologs of the resistance-nodulation-cell division superfamily multidrug efflux pump AcrAB, as well as the regulatory protein AcrR (MHA_0370 to MHA_0372), are also present (41).…”
Section: Resultsmentioning
confidence: 99%
“…1A) (4), we hypothesized that transcription termination in this leader might require Rho. To test this hypothesis, we monitored the effect of the Rho-specific inhibitor bicyclomycin (BCM) (14) on the β-galactosidase activity produced by wild-type Salmonella harboring a plasmid-borne transcriptional fusion between the mgtA leader and a promoterless E. coli lacZ gene driven by the Mg 2+ -insensitive p lac1-6 promoter (4). [We chose a BCM concentration of 20 μg/mL so as to limit effects on bacterial growth.…”
Section: +mentioning
confidence: 99%
“…Because no obvious Rho-independent terminator could be identified within the lysC riboswitch, we wondered if the riboswitch could rely on Rho to terminate transcription prematurely upon lysine binding. We thus performed Northern blot assays in the presence of bicyclomycin, which is known to inhibit specifically the Rho ATP-dependent RNA-binding activity (19), and assessed whether the lysC mRNA level still would be decreased as a function of lysine. No effect of bicyclomycin was observed on the lysine-dependent decrease in the lysC mRNA level (SI Appendix, Fig.…”
Section: Level Of Lysc Mrna Decreases Rapidly In the Presence Of Lysinementioning
confidence: 99%