Fluorescence assay to predict activity of the glycopeptide antibiotics

Vimberg, Vladimir; Gažák, Radek; Szűcs, Zsolt; Borbás, Anikó; Herczegh, Pál; Cavanagh, Jorunn Pauline; Zieglerová, Leona; Závora, Jan; Adámková, Václava; Novotná, Gabriela Balíková

doi:10.1038/s41429-018-0120-5

Cited by 13 publications

(21 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is of great concern that VanZ orthologs were active against TEI pseudoaglycon derivatives, which represent the newest generation of lipoglycopeptides with promising in vitro activity against glycopeptide-resistant strains (Szucs et al, 2017). Similar to ORI, these derivatives show equal competition with FL-TEI and FL-VAN for binding to S. aureus cells, and this result correlates with their activity against vanHAXmediated resistance (Vimberg et al, 2019). Nevertheless, whether the hydrophobic substituents interact with a membrane or with the peptidoglycan needs to be determined for these compounds.…”

Section: Discussionmentioning

confidence: 99%

“…Teicoplanin, vancomycin, oritavancin, and chloramphenicol (Sigma-Aldrich, Germany); dalbavancin (MedChemExpress, Sweden); MA79 (Csávás et al, 2015), ERJ390 (Pintér et al, 2009), and SZZS-12 (Szucs et al, 2017); carbenicillin, gentamicin and erythromycin (Duchefa Biochemie, Netherland); vancomycin BODIPY-FL conjugate (Thermo Fisher Scientific, Germany) and fluorescently labeled teicoplanin (Vimberg et al, 2019).…”

Section: Antibioticsmentioning

confidence: 99%

“…Cells were harvested by centrifugation and resuspended to A 600nm = 1 in 50 mM Tris-HCl buffer (pH = 7.4). Increasing amounts of Bodipy-Vancomycin (Thermo Fisher Scientific, Germany) or Fluorescent Teicoplanin (Vimberg et al, 2019) were added to 1 ml of resuspended cells. Cells were then incubated for 10 min at room temperature with the fluorescent antibiotics, harvested by centrifugation, washed two times with 50 mM Tris-HCl buffer (pH = 7.4), and finally resuspended in 100 µl of the same buffer.…”

Section: Binding Of Fluorescent Vancomycin Andmentioning

confidence: 99%

See 2 more Smart Citations

VanZ Reduces the Binding of Lipoglycopeptide Antibiotics to Staphylococcus aureus and Streptococcus pneumoniae Cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

vanZ, a member of the VanA glycopeptide resistance gene cluster, confers resistance to lipoglycopeptide antibiotics independent of cell wall precursor modification by the vanHAX genes. Orthologs of vanZ are present in the genomes of many clinically relevant bacteria, including Enterococcus faecium and Streptococcus pneumoniae; however, vanZ genes are absent in Staphylococcus aureus. Here, we show that the expression of enterococcal vanZ paralogs in S. aureus increases the minimal inhibitory concentrations of lipoglycopeptide antibiotics teicoplanin, dalbavancin, oritavancin and new teicoplanin pseudoaglycone derivatives. The reduction in the binding of fluorescently labeled teicoplanin to the cells suggests the mechanism of VanZ-mediated resistance. In addition, using a genomic vanZ gene knockout mutant of S. pneumoniae, we have shown that the ability of VanZ proteins to compromise the activity of lipoglycopeptide antibiotics by reducing their binding is a more general feature of VanZ-superfamily proteins.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Antibioticsmentioning

confidence: 99%

Section: Binding Of Fluorescent Vancomycin Andmentioning

confidence: 99%

See 1 more Smart Citation

VanZ Reduces the Binding of Lipoglycopeptide Antibiotics to Staphylococcus aureus and Streptococcus pneumoniae Cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The primary mechanism of action of GPAs is the binding to the d-Ala-d-Ala terminus of peptidoglycan precursors of bacterial cell wall, thus blocking mature cell wall assembly and, ultimately, leading to cell lysis [22,23]. In novel derivatives, the incorporation of a new membrane depolarization and disruption mechanism improves efficacy and evades resistance [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics

et al. 2020

View full text Add to dashboard Cite

Glycopeptide antibiotics (GPAs) are drugs of last resort for treating infections by Gram-positive bacteria. They inhibit bacterial cell wall assembly by binding to the d-Ala-d-Ala terminus of peptidoglycan precursors, leading to cell lysis. Vancomycin and teicoplanin are first generation GPAs, while dalbavancin is one of the few, recently approved, second generation GPAs. In this paper, we developed an in vivo insect model to compare, for the first time, the efficacy of these three GPAs in curing Staphylococcus aureus infection. Differently from previous reports, Bombyx mori larvae were reared at 37 °C, and the course of infection was monitored, following not only larval survival, but also bacterial load in the insect body, hemocyte activity, phenoloxidase activity, and antimicrobial peptide expression. We demonstrated that the injection of S. aureus into the hemolymph of B. mori larvae led to a marked reduction of their survival rate within 24–48 h. GPAs were not toxic to the larvae and cured S. aureus infection. Dalbavancin was more effective than first generation GPAs. Due to its great advantages (i.e., easy and safe handling, low rearing costs, low antibiotic amount needed for the tests, no restrictions imposed by ethical and regulatory issues), this silkworm infection model could be introduced in preclinical phases—prior to the use of mice—accelerating the discovery/development rate of novel GPAs.

show abstract

“…Recently, we introduced a new group of glycopeptide derivatives in which the primary amino function of the teicoplanin pseudoaglycone was replaced [6][7][8]. Figure 1 shows maleimido teicoplanin pseudoaglycone with two propylthiol groups (MA79) and teicoplanin pseudoaglycone derivative with a lipophilic n-decyl chain (ERJ390), both of which exhibited in vitro activity against clinical isolates of S. aureus, coagulase-negative staphylococci (CoNS): Staphylococcus epidermidis and Staphylococcus haemolyticus (including biofilm-producing strains) [9].…”

Section: Introductionmentioning

confidence: 99%

Two Novel Semisynthetic Lipoglycopeptides Active against Staphylococcus aureus Biofilms and Cells in Late Stationary Growth Phase

et al. 2021

Self Cite

View full text Add to dashboard Cite

The increase in antibiotic resistance among Gram-positive bacteria underscores the urgent need to develop new antibiotics. New antibiotics should target actively growing susceptible bacteria that are resistant to clinically accepted antibiotics including bacteria that are not growing or are protected in a biofilm environment. In this paper, we compare the in vitro activities of two new semisynthetic glycopeptide antibiotics, MA79 and ERJ390, with two clinically used glycopeptide antibiotics—vancomycin and teicoplanin. The new antibiotics effectively killed not only exponentially growing cells of Staphylococcus aureus, but also cells in the stationary growth phase and biofilm.

show abstract

Fluorescence assay to predict activity of the glycopeptide antibiotics

Cited by 13 publications

References 12 publications

VanZ Reduces the Binding of Lipoglycopeptide Antibiotics to Staphylococcus aureus and Streptococcus pneumoniae Cells

VanZ Reduces the Binding of Lipoglycopeptide Antibiotics to Staphylococcus aureus and Streptococcus pneumoniae Cells

A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics

Two Novel Semisynthetic Lipoglycopeptides Active against Staphylococcus aureus Biofilms and Cells in Late Stationary Growth Phase

Contact Info

Product

Resources

About