In vitro activity of a novel siderophore- cephalosporin, GT-1 and serine-type β-lactamase inhibitor, GT-055, against escherichia coli, klebsiella pneumoniaeand acinetobacter spp. Panel strains

Le Phuong Nguyen, Naina Adren Pinto, Thao Nguyen Vu, Hyunsook Lee, Young Lag Cho, Jung Hyun Byun, Roshan D’souza, Dongeun Yong

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4 Citations (Scopus)

Abstract

This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-β-lactam β-lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. isolates. GT-1 and GT-1/GT-055 were tested in vitro against comparators among three different characterised panel strain sets. Bacterial resistome and siderophore uptake systems were characterised to elucidate the genetic basis for GT-1 minimum inhibitory concentrations (MICs). GT-1 exhibited in vitro activity (≤2 μg/mL MICs) against many MDR isolates, including extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing E. coli and K. pneumoniae and oxacillinase (OXA)-producing Acinetobacter spp. GT-1 also inhibited strains with mutated siderophore transporters and porins. Although BLI GT-055 exhibited intrinsic activity (MIC 2–8 μg/mL) against most E. coli and K. pneumoniae isolates, GT-055 enhanced the activity of GT-1 against many GT-1–resistant strains. Compared with CAZ- AVI, GT-1/GT-055 exhibited lower MICs against E. coli and K. pneumoniae isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of E. coli, K. pneumoniae and Acinetobacter spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1–resistant strains.

Original languageEnglish
Article number267
JournalAntibiotics
Volume9
Issue number5
DOIs
Publication statusPublished - 2020 May

Bibliographical note

Funding Information:
This work was supported by the BioNano Health-Guard Research Center, funded by the Ministry of Science, ICT and Future Planning (MSIP) of Korea as a Global Frontier Project (H-GUARD_2014M3A6B2060509); by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through the Agricultural Microbiome R&D Program, funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA) (918003-4); and by a grant from the National Institute of Health, Korea (2019ER540300R514931). This work was also supported by the Brain Korea 21 plus Project for Medical Science, Yonsei University.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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