In vivo antibacterial activity and pharmacological properties of the membrane-active glycopeptide antibiotic YV11455

Yarlagadda, Venkateswarlu; Konai, Mohini M.; Manjunath, Goutham B.; Prakash, Relekar G.; Mani, Bhuvana; Krishnamoorthy, P.; Ranjan, Shome B.; Ravikumar, Raju; Chakraborty, Subhankari Prasad; Roy, Somenath; Haldar, Jayanta

doi:10.1016/j.ijantimicag.2015.02.013

Cited by 23 publications

(30 citation statements)

References 28 publications

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“…The antibacterial activity of the test compounds was measured by the broth microdilution method and the MIC was calculated as per previously published protocols [5,13,14].…”

Section: In Vitro Susceptibility Studiesmentioning

confidence: 99%

“…In vivo antibacterial activity was assessed using the NMT infection model as described previously [14]. Briefly, mice were rendered neutropenic (ca.…”

Section: Neutropenic Mouse Thigh (Nmt) Infection Modelmentioning

confidence: 99%

“…Blood samples were collected from mice by retro-orbital aspiration and were placed into heparinised tubes at 0.083, 0.5, 1, 2, 3, 4, 6, 8 and 24 h after dosing (n = 3 per data point). Plasma was separated by centrifugation and drug plasma concentrations were measured by microbiological assay with Bacillus subtilis as the test organism [14]. The lower limit of detection of the assay was 1.25 g/mL (see Supplementary Fig.…”

Section: Single-dose Pharmacokinetic Studymentioning

confidence: 99%

“…S1). Pharmacokinetic parameters, including half-life (t 1/2 ), area under the concentration-time curve (AUC) and peak plasma concentration (C max ) were calculated using a non-compartmental model [14]. The AUC was estimated up to 24 h and t 1/2 was calculated.…”

Section: Single-dose Pharmacokinetic Studymentioning

confidence: 99%

“…injection of YV4465 at 12 mg/kg (dosage of >ED 2-log kill ) in 0.2 mL of sterilised saline. Ten mice were sacrificed at 48 h and rest of the mice at 14 days to collect blood samples for analysis of biochemical parameters such as alanine aminotransferase (ALT), urea nitrogen, creatinine, and sodium, potassium and chloride ion levels [14]. Blood samples were analysed at Gokula Metropolis Clinical Laboratories (Bengaluru, India).…”

Section: Acute Toxicitymentioning

confidence: 99%

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In vivo efficacy and pharmacological properties of a novel glycopeptide (YV4465) against vancomycin-intermediate Staphylococcus aureus

Yarlagadda

Konai

Krishnamoorthy

et al. 2015

International Journal of Antimicrobial Agents

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“…The antibacterial activity of the test compounds was measured by the broth microdilution method and the MIC was calculated as per previously published protocols [5,13,14].…”

Section: In Vitro Susceptibility Studiesmentioning

confidence: 99%

“…In vivo antibacterial activity was assessed using the NMT infection model as described previously [14]. Briefly, mice were rendered neutropenic (ca.…”

Section: Neutropenic Mouse Thigh (Nmt) Infection Modelmentioning

confidence: 99%

Section: Single-dose Pharmacokinetic Studymentioning

confidence: 99%

Section: Single-dose Pharmacokinetic Studymentioning

confidence: 99%

Section: Acute Toxicitymentioning

confidence: 99%

See 3 more Smart Citations

In vivo efficacy and pharmacological properties of a novel glycopeptide (YV4465) against vancomycin-intermediate Staphylococcus aureus

Yarlagadda

Konai

Krishnamoorthy

et al. 2015

International Journal of Antimicrobial Agents

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Membrane Disruption and Enhanced Inhibition of Cell‐Wall Biosynthesis: A Synergistic Approach to Tackle Vancomycin‐Resistant Bacteria

et al. 2015

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Resistance to glycopeptide antibiotics, the drugs of choice for life‐threatening bacterial infections, is on the rise. In order to counter the threat of glycopeptide‐resistant bacteria, we report development of a new class of semi‐synthetic glycopeptide antibiotics, which not only target the bacterial membrane but also display enhanced inhibition of cell‐wall biosynthesis through increased binding affinity to their target peptides. The combined effect of these two mechanisms resulted in improved in vitro activity of two to three orders of magnitude over vancomycin and no propensity to trigger drug resistance in bacteria. In murine model of kidney infection, the optimized compound was able to bring bacterial burden down by about 6 logs at 12 mg kg−1 with no observed toxicity. The results furnished in this report emphasize the potential of this class of compounds as future antibiotics for drug‐resistant Gram‐positive infections.

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A Vancomycin Derivative with a Pyrophosphate‐Binding Group: A Strategy to Combat Vancomycin‐Resistant Bacteria

et al. 2016

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Vancomycin, the drug of last resort for Gram‐positive bacterial infections, has also been rendered ineffective by the emergence of resistance in such bacteria. To combat the threat of vancomycin‐resistant bacteria (VRB), we report the development of a dipicolyl–vancomycin conjugate (Dipi‐van), which leads to enhanced inhibition of cell‐wall biosynthesis in VRB and displays in vitro activity that is more than two orders of magnitude higher than that of vancomycin. Conjugation of the dipicolyl moiety, which is a zinc‐binding ligand, endowed the parent drug with the ability to bind to pyrophosphate groups of cell‐wall lipids while maintaining the inherent binding affinity for pentapeptide termini of cell‐wall precursors. Furthermore, no detectable resistance was observed after several serial passages, and the compound reduced the bacterial burden by a factor of 5 logs at 12 mg kg−1 in a murine model of VRB kidney infection. The findings presented in this report stress the potential of our strategy to combat VRB infections.

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In vivo antibacterial activity and pharmacological properties of the membrane-active glycopeptide antibiotic YV11455

Cited by 23 publications

References 28 publications

In vivo efficacy and pharmacological properties of a novel glycopeptide (YV4465) against vancomycin-intermediate Staphylococcus aureus

In vivo efficacy and pharmacological properties of a novel glycopeptide (YV4465) against vancomycin-intermediate Staphylococcus aureus

Membrane Disruption and Enhanced Inhibition of Cell‐Wall Biosynthesis: A Synergistic Approach to Tackle Vancomycin‐Resistant Bacteria

A Vancomycin Derivative with a Pyrophosphate‐Binding Group: A Strategy to Combat Vancomycin‐Resistant Bacteria

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