Effect of a Metalloantibiotic Produced by Pseudomonas aeruginosa on Klebsiella pneumoniae Carbapenemase (KPC)-producing K. pneumoniae

Kerbauy, Gilselena; Vivan, Ana Carolina Polano; Simões, Glenda Cavalari; Simionato, Ane Stéfano; Pelisson, Marsileni; Vespero, Eliana Carolina; Costa, Sílvia Figueiredo; Andrade, Celia G.T. de J.; Barbieri, Daiane M.; Mello, João Carlos Palazzo de; Morey, Alexandre Tadachi; Yamauchi, Lucy Megumi; Yamada‐Ogatta, Sueli Fumie; Oliveira, Admilton Gonçalves de; Andrade, Galdino

doi:10.2174/138920101704160215171649

Cited by 24 publications

(26 citation statements)

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“…To evaluate minimum inhibitory concentration of BRACO-19 for K. pneumoniae , MTT-based growth inhibition assay was performed, as per the modified protocol mentioned elsewhere ( Kerbauy et al, 2016 ; Lalitha et al, 2017 ). Briefly, the K. pneumoniae ATCC 700603 strain procured from HiMedia was revived and cultured in BHI broth media (HiMedia) till it reached an optical density of 0.5 at 600 nm (O.D.…”

Section: Methodsmentioning

confidence: 99%

Conserved G-Quadruplex Motifs in Gene Promoter Region Reveals a Novel Therapeutic Approach to Target Multi-Drug Resistance Klebsiella pneumoniae

et al. 2020

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An opportunistic pathogen, Klebsiella pneumoniae is known to cause life-threating nosocomial infection with a high rate of morbidity and mortality. Evolutions of multi-drug-resistant and hyper-virulent strains of K. pneumoniae make the situation worse. Currently, there is no incisive drug molecule available for drug-resistant hyper-virulent K. pneumoniae infection that emphasizes the need for identification of novel and more promising drug targets in K. pneumoniae . Recently, various non-canonical structures of nucleic acids especially G-quadruplex (G4) motifs have been identified as potential therapeutic targets against several human pathogenic bacteria and viruses including Mycobacterium tuberculosis , Streptococcus pneumoniae , human immunodeficiency virus (HIV), Ebola, and Nipah. Therefore, in present study we screened the K. pneumoniae genomes for identification of evolutionary conserved G4 structure-forming motifs as promising anti-bacterial drug targets. Bioinformatics analysis revealed the presence of six highly conserved G4 motifs in the promoter region of five essential genes that play a critical role in nutrient transport and metabolism. Biophysical studies showed the formation of G4 structure by these conserved motifs. Circular Dichroism melting analysis showed the stabilization of these G4 motifs by a well-known G4-stabilizing agent, BRACO-19. The stabilization of these motifs by BRACO-19 was also able to stop the primer extension process, which is an essential phenomenon for expression of the G4-harboring gene. The addition of G4-specific ligand at low micromolar range was observed to be lethal for the growth of this bacteria and negatively controlled the expression of the G4-harboring genes via G4 structure stabilization. These observations strengthen the formation of G4 structures by the predicted G4 motif in vivo , which can be stabilized by G4 ligands like BRACO-19. This stabilization of G4 structures can attenuate the expression of G4-harboring essential genes and thus play a critical role in the regulation of gene expression. Thus, taking all given result in consideration, for the first time, this study showed the new therapeutic avenue for combating K. pneumoniae infection by characterizing the conserved G4 motifs as promising therapeutic targets.

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Section: Methodsmentioning

confidence: 99%

Conserved G-Quadruplex Motifs in Gene Promoter Region Reveals a Novel Therapeutic Approach to Target Multi-Drug Resistance Klebsiella pneumoniae

et al. 2020

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“…Valence) in Astorga, Brazil (Rampazo, 2004), deposited in GenBank under accession number GQ342301 (Kerbauy et al, 2016). The strain was cryopreserved in liquid nitrogen in sterilized distilled water (SDW) plus 20% glycerol.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Phenazine-1-Carboxylic Acid on Mycelial Growth of Botrytis cinerea Produced by Pseudomonas aeruginosa LV Strain

et al. 2017

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One of the most important postharvest plant pathogens that affect strawberries, grapes and tomatoes is Botrytis cinerea, known as gray mold. The fungus remains in latent form until spore germination conditions are good, making infection control difficult, causing great losses in the whole production chain. This study aimed to purify and identify phenazine-1-carboxylic acid (PCA) produced by the Pseudomonas aeruginosa LV strain and to determine its antifungal activity against B. cinerea. The compounds produced were extracted with dichloromethane and passed through a chromatographic process. The purity level of PCA was determined by reversed-phase high-performance liquid chromatography semi-preparative. The structure of PCA was confirmed by nuclear magnetic resonance and electrospray ionization mass spectrometry. Antifungal activity was determined by the dry paper disk and minimum inhibitory concentration (MIC) methods and identified by scanning electron microscopy and confocal microscopy. The results showed that PCA inhibited mycelial growth, where MIC was 25 μg mL-1. Microscopic analysis revealed a reduction in exopolysaccharide (EPS) formation, showing distorted and damaged hyphae of B. cinerea. The results suggested that PCA has a high potential in the control of B. cinerea and inhibition of EPS (important virulence factor). This natural compound is a potential alternative to postharvest control of gray mold disease.

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“…The dissemination and emergence of KPC producers is a serious threat to public health because it drastically limits the treatment options2050. It not only confers resistance to carbapenems, but also to almost all other β-lactams.…”

Section: Methods For Kpc Identificationmentioning

confidence: 99%

A structural, epidemiological & genetic overview of Klebsiella pneumoniae carbapenemases (KPCs)

swathi

Chikala

et al. 2016

Indian J Med Res

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Klebsiella pneumoniae carbapenemases (KPCs) are plasmid encoded carbapenem hydrolyzing enzymes which have the potential to spread widely through gene transfer. The instability of upstream region of blaKPC accelerates emergence of different isoforms. Routine antibiotic susceptibility testing failed to detect KPC producers and some commercial kits have been launched for early identification of KPC producers. Notable among the drugs under development against KPC are mostly derivatives of polymixin; β-lactamase inhibitor NXL104 with combination of oxyimino cephalosporin as well as with ceftazidime; a novel tricyclic carbapenem, LK-157, potentially useful against class A and class C enzymes; BLI-489-a bicyclic penem derivative; PTK-0796, a tetracycline derivative and ACHN-490. Combination therapy might be preferable to control KPC infections in immediate future. Clinicians are likely to opt for unconventional combinations of antibiotics to treat KPC infections because of unavailability of alternative agents. The KPCs have become endemic in many countries but there is no optimal treatment recommendation available for bacteria expressing KPCs. Reports of outbreaks involving KPCs have focused mainly on laboratory identification, empirical treatment outcomes and molecular epidemiology. This review includes information on the emergence of KPC variants, limitations of phenotyping methods, available molecular methods for identification of the KPC variants and treatment options highlighting the drugs under development.

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Effect of a Metalloantibiotic Produced by Pseudomonas aeruginosa on Klebsiella pneumoniae Carbapenemase (KPC)-producing K. pneumoniae

Cited by 24 publications

References 0 publications

Conserved G-Quadruplex Motifs in Gene Promoter Region Reveals a Novel Therapeutic Approach to Target Multi-Drug Resistance Klebsiella pneumoniae

Conserved G-Quadruplex Motifs in Gene Promoter Region Reveals a Novel Therapeutic Approach to Target Multi-Drug Resistance Klebsiella pneumoniae

The Effect of Phenazine-1-Carboxylic Acid on Mycelial Growth of Botrytis cinerea Produced by Pseudomonas aeruginosa LV Strain

A structural, epidemiological & genetic overview of Klebsiella pneumoniae carbapenemases (KPCs)

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