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Antimicrobial Resistance (AMR) Platform Research & Services

Housed at the Institute of Infectious Disease & Molecular Medicine (IDM)

 

Antimicrobial Resistance (AMR) Biology Platform

H3D has joined the global antimicrobial resistance (AMR) response, by collaborating with key partners and in building an AMR screening platform of ESKAPE pathogens (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae). This builds on our existing expertise in infectious disease drug discovery, H3D has now has facilities for AMR biology and a screening centre to test novel therapies, small molecules and natural products as starting points for potential AMR treatments. New protocols for AMR work include phenotypic screening, resistance profiling, mechanism of action studies including Target-ID and validation.

See the table below for additional details, including average turnaround time and control(s). For assays where an average turnaround time/control(s) are not available, this indicates that turnaround time is dependent on your unique experimental design and conditions; please book a consultation for an estimated turnaround time or additional information.

 

AMR Single Point (SP) Assays

Detect a single target for one or more microbial strains. Antimicrobial resistance is a top threat to global health and consideration of a activity against a single target in multiple microbial strains significantly furthers understanding of the resistance mechanisms that play a key role in substantiating this serious global problem.

  • Single point assay (6 strains)
  • Single point assay (1 strain)

 

AMR Dose Response Assays

  • ESKAPE panel 6 strains
    • ESKAPE pathogens are a group of highly aggressive and resistant organisms and include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. This group comprises the leading causes of nosocomial (hospital or healthcare associated) infections throughout the world.
  • The numbers specified for the following strains refer to widely-accepted recommended strains for antibiotic susceptibility testing, and are available for selection in H3D AMR Dose Response Assays:
    • Escherichia coli 25922
    • Staphylococcus aureus 25923
    • Klebsiella pneumoniae 1705
    • Acinetobacter baumannii 19606
    • Pseudomonas aeruginosa 27853
    • Enterobacter clocae 700323
    • Escherichia coli TolC mutant Assay (efflux pump)

 

AMR Clinical Strain Panel

H3D contains a collection of clinically isolated ESKAPE pathogens with various resistance profiles. A unique feature of this panel is that it represents the African population. These strains are available for screening in a single point and/or dose-response assay. The results from phenotypic screening assays can inform a project on the specificity and selectivity of samples against these strains.

 

Data from these assays can be used for lead optimization and drug candidate evaluation and results from these assays thereby inform key decision making and experimental design of human and/or animal in vivo studies. These assays must be combined with ADMET, DMPK, and other preliminary in vitro and in vivo assays in order to elucidate the necessary data for such key decision making and experimental design.

 

Assay Group Assay Specifications Average Turnaround Time Control(s)
AMR single pt Single point (6 strains) 2 weeks untreated bacterial & media sterility control wells 
AMR single pt Single point (1 strain) 2 weeks untreated bacterial & media sterility control wells 
AMR Dose Response ESKAPE panel 6 strains 2 weeks untreated bacterial & media sterility control wells 
AMR Dose Response Escherichia coli 25922   untreated bacterial & media sterility control wells  
AMR Dose Response Staphylococcus aureus 25923   untreated bacterial & media sterility control wells 
AMR Dose Response Klebsiella pneumoniae 1705   untreated bacterial & media sterility control wells 
AMR Dose Response Acinetobacter baumannii 19606   untreated bacterial & media sterility control wells 
AMR Dose Response Pseudomonas aeruginosa 27853   untreated bacterial & media sterility control wells 
AMR Dose Response Enterobacter clocae 700323   untreated bacterial & media sterility control wells  
AMR Dose Response Escherichia coli TolC mutant Assay (efflux pump)   untreated bacterial & media sterility control wells  
AMR Clinical Strain Panel Single pt or Dose-Response 26 strains   untreated bacterial & media sterility control wells  
AMR Biology Studies
 
Select Relevant H3D Authored Publications

Bellini D, Koekemoer L, Newman H, Dowson CG. Novel and Improved Crystal Structures of H. influenzae, E. coli and P. aeruginosa Penicillin-Binding Protein 3 (PBP3) and N. gonorrhoeae PBP2: Toward a Better Understanding of β-Lactam Target-Mediated Resistance. J Mol Biol. 2019 Aug 23;431(18):3501-3519. doi: 10.1016/j.jmb.2019.07.010. Epub 2019 Jul 10. PMID: 31301409.

Price, N.P.J., Jackson, M.A., Singh, V. et al. Synergistic enhancement of beta-lactam antibiotics by modified tunicamycin analogs TunR1 and TunR2. J Antibiot 72, 807–815 (2019). https://doi.org/10.1038/s41429-019-0220-x

 
Additional References supporting H3D's materials & methods:

CLSI, 2017. Performance Standards for Antimicrobial Susceptibility Testing. 27th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2017