2018
DOI: 10.3390/antibiotics7010023
|View full text |Cite
|
Sign up to set email alerts
|

The Macromolecular Machines that Duplicate the Escherichia coli Chromosome as Targets for Drug Discovery

Abstract: DNA replication is an essential process. Although the fundamental strategies to duplicate chromosomes are similar in all free-living organisms, the enzymes of the three domains of life that perform similar functions in DNA replication differ in amino acid sequence and their three-dimensional structures. Moreover, the respective proteins generally utilize different enzymatic mechanisms. Hence, the replication proteins that are highly conserved among bacterial species are attractive targets to develop novel anti… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

0
29
0

Year Published

2018
2018
2022
2022

Publication Types

Select...
6
2

Relationship

0
8

Authors

Journals

citations
Cited by 24 publications
(29 citation statements)
references
References 286 publications
(378 reference statements)
0
29
0
Order By: Relevance
“…Antibiotic-resistance presents a growing threat to public health (Rice, 2008(Rice, , 2010Devasahayam et al, 2010;Moellering, 2011) and drives the need for discovery of new antibacterials that act via novel mechanisms (Robinson et al, 2012;Kaguni, 2018). A prominent group of bacteria harboring multidrug resistance and causing nosocomial infections worldwide are known as the "ESKAPE" pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.).…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Antibiotic-resistance presents a growing threat to public health (Rice, 2008(Rice, , 2010Devasahayam et al, 2010;Moellering, 2011) and drives the need for discovery of new antibacterials that act via novel mechanisms (Robinson et al, 2012;Kaguni, 2018). A prominent group of bacteria harboring multidrug resistance and causing nosocomial infections worldwide are known as the "ESKAPE" pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.).…”
Section: Introductionmentioning
confidence: 99%
“…A rich source of potential new targets is the bacterial DNA replication machinery, which carefully orchestrates a complex series of protein-protein and protein-DNA interactions to faithfully replicate DNA prior to cell division (Robinson et al, 2012;Kaguni, 2018). Central in this process is the DNA polymerase III  subunit, also known as the  sliding clamp (), a ringshaped homodimeric protein (Kong et al, 1992) that encircles double-stranded DNA (dsDNA) (Georgescu et al, 2008a), where it serves as an interaction hub that recruits protein-binding partners to DNA.…”
Section: Introductionmentioning
confidence: 99%
“…Formaldehyde produces a wide variety of lesions, so we are unsure whether it is the production of DPCs that promotes mutagenesis. Ciprofloxacin specifically inhibits type II topoisomerases [44] for which E. coli has two, DNA gyrase and Topoisomerase IV, and traps the covalent cleaved complex [45]. Because ciprofloxicin inhibits DNA replication, we do not know whether its mutagenic effect is due to general replication inhibition rather the production of DPCs.…”
Section: Discussionmentioning
confidence: 99%
“…The QS gene lasR regulates the expression of virulence factors in P. aeruginosa and therefore represents a particularly interesting therapeutic target [79]. Mutations of gyrA are common in fluroquinolone-resistant clinical strains [80] and inhibitors of gyrA expression are being explored as a pharmacological target [81,82]. In summary, 3pMap predicts regulation via transcriptional attenuation at hundreds of genes in P. aeruginosa, revealing potential new targets for molecular therapeutic intervention.…”
Section: Predicting Potential Regulatory Elements That Cause Transcrimentioning
confidence: 99%