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Activity of siderophores against drug-resistant Gram-positive and Gram-negative bacteria.

ABSTRACT: Infections by drug-resistant bacteria are life-threatening. As iron is a vital element for the growth of bacteria, iron-chelating agents (siderophores) can be used to arrest their multiplication. Exogenous siderophores - exochelin-MS and deferoxamine-B - were evaluated for their inhibitory activity against methicillin-resistant Staphylococcus aureus and metallo-β-lactamase producers - Pseudomonas aeruginosa and Acinetobacter baumannii - by disc diffusion, micro-broth dilution, and turbidimetric growth assays. The drug-resistant isolates were inhibited by the synergistic activity of siderophores and antibiotics. Minimum inhibitory concentration of exochelin-MS+ampicillin for different isolates was between 0.05 and 0.5 mg/mL. Minimum inhibitory concentration of deferoxamine-B+ampicillin was 1.0 mg/mL and greater. Iron-chelation therapy could provide a complementary approach to overcome drug resistance in pathogenic bacteria.

SUBMITTER: Gokarn K

PROVIDER: S-EPMC5765970 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Activity of siderophores against drug-resistant Gram-positive and Gram-negative bacteria.

Gokarn Karuna K Pal Ramprasad B RB

Infection and drug resistance 20180109

Infections by drug-resistant bacteria are life-threatening. As iron is a vital element for the growth of bacteria, iron-chelating agents (siderophores) can be used to arrest their multiplication. Exogenous siderophores - exochelin-MS and deferoxamine-B - were evaluated for their inhibitory activity against methicillin-resistant Staphylococcus aureus and metallo-β-lactamase producers - Pseudomonas aeruginosa and Acinetobacter baumannii - by disc diffusion, micro-broth dilutio ...[more]

PMID: 29386910

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Project description:Gepotidacin is a first-in-class, novel triazaacenaphthylene antibiotic that inhibits bacterial DNA replication and has in vitro activity against susceptible and drug-resistant pathogens. Reference in vitro methods were used to investigate the MICs and minimum bactericidal concentrations (MBCs) of gepotidacin and comparator agents for Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli Gepotidacin in vitro activity was also evaluated by using time-kill kinetics and broth microdilution checkerboard methods for synergy testing and for postantibiotic and subinhibitory effects. The MIC90 of gepotidacin for 50 S. aureus (including methicillin-resistant S. aureus [MRSA]) and 50 S. pneumoniae (including penicillin-nonsusceptible) isolates was 0.5 μg/ml, and for E. coli (n = 25 isolates), it was 4 μg/ml. Gepotidacin was bactericidal against S. aureus, S. pneumoniae, and E. coli, with MBC/MIC ratios of ≤4 against 98, 98, and 88% of the isolates tested, respectively. Time-kill curves indicated that the bactericidal activity of gepotidacin was observed at 4× or 10× MIC at 24 h for all of the isolates. S. aureus regrowth was observed in the presence of gepotidacin, and the resulting gepotidacin MICs were 2- to 128-fold higher than the baseline gepotidacin MICs. Checkerboard analysis of gepotidacin combined with other antimicrobials demonstrated no occurrences of antagonism with agents from multiple antimicrobial classes. The most common interaction when testing gepotidacin was indifference (fractional inhibitory concentration index of >0.5 to ≤4; 82.7% for Gram-positive isolates and 82.6% for Gram-negative isolates). The postantibiotic effect (PAE) of gepotidacin was short when it was tested against S. aureus (≤0.6 h against MRSA and MSSA), and the PAE-sub-MIC effect (SME) was extended (>8 h; three isolates at 0.5× MIC). The PAE of levofloxacin was modest (0.0 to 2.4 h), and the PAE-SME observed varied from 1.2 to >9 h at 0.5× MIC. These in vitro data indicate that gepotidacin is a bactericidal agent that exhibits a modest PAE and an extended PAE-SME against Gram-positive and -negative bacteria and merits further study for potential use in treating infections caused by these pathogens.

Dataset Information

Activity of siderophores against drug-resistant Gram-positive and Gram-negative bacteria.

Publications

Activity of siderophores against drug-resistant Gram-positive and Gram-negative bacteria.

Similar Datasets

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