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Polyphosphate synthesis as a target for novel antibiotics

dc.contributor.authorChávez F.P.
dc.contributor.authorLagos C.F.
dc.contributor.authorReyes-Parada M.
dc.contributor.authorGuiliani N.
dc.contributor.authorJerez C.A.
dc.date.accessioned2020-09-02T22:14:52Z
dc.date.available2020-09-02T22:14:52Z
dc.date.issued2011
dc.identifier10.2174/157340811798807605
dc.identifier.citation7, 3, 163-168
dc.identifier.issn15734080
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4020
dc.descriptionInorganic polyphosphate (polyP) is a biopolymer of tens or hundreds of phosphate (Pi) residues linked by highenergy phosphoanhydride bonds. PolyP has been studied mainly in prokaryotes but it is present in all species of the three domains of life. In bacteria, polyP and its processing enzymes play important roles in cellular metabolism as well as in pathogenesis. The genomes of many bacterial species, including pathogens, encode orthologs of the main polyPsynthesizing enzyme, PPK1. This enzyme has been studied in E. coli and its metabolic inhibitors have been reported. The high degree of identity between the PPK1 orthologs in some of the major pathogenic species has prompted the knockout of their ppk1 genes to determine the dependence of virulence on polyP. Although viable, mutants lacking the ppk1 gene have reduced levels of polyP and exhibit multiple structural, functional and virulence defects. The emergence of multi-drug resistant (MDR) bacteria is the result of antibiotic overuse. Therefore, novel approaches are much needed to tackle them. One of these combines the reduction of bacterial virulence while simultaneously increasing susceptibility to host defenses instead of killing the pathogen. Considering that no PPK1 orthologs have been identified in higher-order eukaryotes, PPK1 exhibits an enormous potential as a novel target for antimicrobial drug design. In this review we focus on the current state of the art regarding polyP deficiency in pathogenic bacteria and attempts to design inhibitors targeting enzymes responsible for the synthesis of polyP in bacteria. © 2011 Bentham Science Publishers.
dc.language.isoen
dc.subjectAntibiotics
dc.subjectChemical biology
dc.subjectIn silico drug design
dc.subjectPathogenic bacteria
dc.subjectPolyphosphate
dc.subjectPolyphosphate kinase 1
dc.subjectPpk1 inhibitors
dc.subjectVirulence
dc.subjectadenosine 5 phosphate derivative
dc.subjectadenosine diphosphate
dc.subjectadenosine triphosphate
dc.subjectantibiotic agent
dc.subjectbacterial enzyme
dc.subjectguanidine
dc.subjectpolyphosphate
dc.subjectpolyphosphate kinase 1
dc.subjectpolyphosphate kinase 1 inhibitor
dc.subjectpolyphosphate kinase 2
dc.subjectpyrophosphate
dc.subjectunclassified drug
dc.subjectantibiotic sensitivity
dc.subjectbacterial gene
dc.subjectbacterial virulence
dc.subjectdrug design
dc.subjectdrug protein binding
dc.subjectdrug synthesis
dc.subjectdrug targeting
dc.subjectenzyme inhibition
dc.subjectEscherichia coli
dc.subjectgene deletion
dc.subjectHelicobacter pylori
dc.subjectIC 50
dc.subjectMycobacterium tuberculosis
dc.subjectNeisseria meningitidis
dc.subjectnonhuman
dc.subjectprotein structure
dc.subjectreview
dc.subjectShigella flexneri
dc.subjectVibrio cholerae
dc.subjectBacteria (microorganisms)
dc.subjectEukaryota
dc.subjectProkaryota
dc.titlePolyphosphate synthesis as a target for novel antibiotics
dc.typeReview


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