An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity

Haydon, David J.; Stokes, Neil R.; Ure, Rebecca; Galbraith, Greta; Bennett, James M.; Brown, David R.; Baker, Patrick J.; Barynin, V.V.; Rice, David W.; Sedelnikova, S.E.; Heal, Jonathan R.; Sheridan, J. M.; Aiwale, Sachin T.; Chauhan, Pramod K.; Srivastava, A. K.; Taneja, Amit; Collins, Ian; Errington, Jeff; Czaplewski, Lloyd G.

doi:10.1126/science.1159961

Cited by 402 publications

(538 citation statements)

References 17 publications

Supporting

Mentioning

497

Contrasting

Unclassified

Order By: Relevance

“…35 Thus, FtsZ represents a prime target for specific bacterial inhibition to prevent replication, while eliciting minimal adverse effects to the eukaryotic host. It was during a high-throughput screening for such an inhibitor that the utility of the otherwise 'toxic' viriditoxin was first appreciated.…”

Section: Viriditoxin: Inhibition Of the Ftsz Protein And Disruption Omentioning

confidence: 99%

“…The rotational energy barriers of 34 and 35 were found to be 199 kJ.mol -1 and 201 kJ.mol -1 respectively, consistent with experimental data showing thermal interconversion of the two could not be achieved even by heating at 100 °C for 1 hour. 76 Figure 10: The known structure of xiamycin A (33), and determined structures of dixiamycin A (34) dixiamycin B (35), and an unnamed C-N linked xiamycin dimer (36), of which both the M and P isomers were isolated.…”

Section: Dixiamycins: Atropisomeric N-c and N-n Coupled Dimers From Mmentioning

confidence: 99%

See 1 more Smart Citation

A twist of nature – the significance of atropisomers in biological systems

2015

View full text Add to dashboard Cite

. (2015). A twist of nature-the significance of atropisomers in biological systems. Natural Product Reports: a journal of current development in bioorganic chemistry, 32 (11), 1562-1583. A twist of nature-the significance of atropisomers in biological systems AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized. AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized.

show abstract

Section: Viriditoxin: Inhibition Of the Ftsz Protein And Disruption Omentioning

confidence: 99%

Section: Dixiamycins: Atropisomeric N-c and N-n Coupled Dimers From Mmentioning

confidence: 99%

A twist of nature – the significance of atropisomers in biological systems

2015

View full text Add to dashboard Cite

show abstract

“…FtsZ, a bacterial protein essential for cell division (Errington et al, 2003), was recently targeted with a new class of antibiotic (Haydon et al, 2008). Furthermore, DNA topoisomerase I, present in all bacteria (Forterre et al, 2007) and responsible for removal of excess transcriptionally induced negative DNA supercoiling (Viard and de la Tour, 2007) is sensitive to a few known antibiotics.…”

Section: Pocillopora Damicornis Mucus Contains a Variety Ofmentioning

confidence: 99%

Coral-mucus-associated Vibrio integrons in the Great Barrier Reef: genomic hotspots for environmental adaptation

et al. 2011

View full text Add to dashboard Cite

Integron cassette arrays in a dozen cultivars of the most prevalent group of Vibrio isolates obtained from mucus expelled by a scleractinian coral (Pocillopora damicornis) colony living on the Great Barrier Reef were sequenced and compared. Although all cultivars showed 499% identity across recA, pyrH and rpoB genes, no two had more than 10% of their integron-associated gene cassettes in common, and some individuals shared cassettes exclusively with distantly-related members of the genus. Of cassettes shared within the population, a number appear to have been transferred between Vibrio isolates, as assessed by phylogenetic analysis. Prominent among the mucus Vibrio cassettes with potentially inferable functions are acetyltransferases, some with close similarity to known antibiotic-resistance determinants. A subset of these potential resistance cassettes were shared exclusively between the mucus Vibrio cultivars, Vibrio coral pathogens and human pathogens, thus illustrating a direct link between these microbial niches through exchange of integron-associated gene cassettes.

show abstract

“…Inhibitors of FtsZ have been reported. [26][27][28][29][30][31] Edeine B 1 is a potentially useful tool for studying the mechanism of bacterial cell division.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Septation in Bacillus subtilis by a Peptide Antibiotic, Edeine B1

Shimotohno

Kawamura

Natori

et al. 2010

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The antibiotics, edeine A 1 and B 1 , are well-known inhibitors of protein biosynthesis in both prokaryote and eukaryote cells. Edeine A 1 and B 1 show almost the same biological activity. We show herein that edeine B 1 exhibits a lethal action in Bacillus subtilis, inhibiting septation via a mechanism different from the inhibition of protein synthesis by this antibiotic.The complex process of cell division is closely interconnected with other cellular processes. Chromosomal DNA replication, nuclear division, and cell division must be coordinated in time and space. DNA metabolism plays a pivotal role in the cell division events controlled by the partitioning of newly replicated chromosomes to daughter cells. This involves chromosomal DNA replication, the positioning of a septum at the midpoint of the cell, the assembly of cytoskeletal elements, and the cleavage of the septum after chromosome segregation. Genetic studies have unraveled the process of cell division by the analysis of filamenting temperaturesensitive mutants. In prokaryotes, filamenting temperaturesensitive (fts) genes produce the proteins essential for cell division. Known fts mutants include ftsA, ftsI, ftsK, ftsL, ftsN, ftsW and ftsZ. [1][2][3][4][5][6][7][8] Inhibitors of protein synthesis exhibit bacteriostatic action except for the aminoglycoside (AG) antibiotics, 9) suggesting that the inhibition of protein synthesis by AG antibiotics is not directly involved in their bactericidal action. The bactericidal action of AG antibiotic is assumed to be based on their inhibition of DNA replication. AG antibiotic blocks the initiation of DNA replication, 10) and interrupts oriC-membrane attachment. 11) The oriC-membrane attachment [12][13][14] is crucial for subsequent initiation of DNA replication, chromosome segregation, and septation of bacterial cells. Blocking DNA replication is known to lead to the save our ships (SOS) response in Escherichia coli, thereby inhibiting cell division. 15) We demonstrate herein that edeine B 1 inhibits cell division, exerting its bactericidal action by inhibiting FtsZ assembly, independently of its inhibitory effect on protein synthesis. MATERIALS AND METHODSPurification of Edeine B 1 Edeine B 1 was isolated from a culture filtrate of Bacillus brevis TTO2-8. The purified edeine B 1 yielded a single TLC spot, a single HPLC peak and the predicted structure based on NMR and FAB-MAS analysis. Edeine B 1 is a linear basic oligopeptide antibiotic consisting of five amino acid residues (isotyrosine, isoserine, a,b-diaminopropionic acid, 2,6-diamino-7-hydroxyazelanic acid, and glycine) and an organic base (guanylspermidine) produced by B. brevis. 16,17) Bacterial Strains B. subtilis 168 and mutant FtsZ ts1 (a temperature sensitive mutant of B. subtilis 168) were used.Viable Cell Number The viable cell number was counted by plating on LB (Luria-Bertani) agar, and recording the number of colonies that developed after 24 h incubation.Western Blotting Anti-FtsZ rabbit antibody raised against a chemically synthesized carboxyl t...

show abstract

An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity

Cited by 402 publications

References 17 publications

A twist of nature – the significance of atropisomers in biological systems

A twist of nature – the significance of atropisomers in biological systems

Coral-mucus-associated Vibrio integrons in the Great Barrier Reef: genomic hotspots for environmental adaptation

Inhibition of Septation in Bacillus subtilis by a Peptide Antibiotic, Edeine B1

Contact Info

Product

Resources

About