ANTRUK’s Research Programmes

Developing a new antibiotic therapy by the early 2020’s

Antibiotic Research UK’s research programmes

Typically it can take up to 15 years and expenditure of many hundreds of millions of pounds to develop a new drug. ANTRUK aims to significantly reduce these timelines and costs by using smart approaches which will be very different to conventional drug development procedures. The Charity’s research focus initially will be on preserving our existing antibiotics rather than trying to find new ones.

  •  Multi-drug resistant (MDR) Gram-negative bacteria are the major risk to modern medicine.
  •  About 50% of all hospital infections are due to Gram-negative bacteria
  •  Of particular concern are antibiotic resistant bacteria associated with four different species, Klebsiella pneuomoniaePseudomonas aeruginosa, Escherichia coli and Acinetobacter baumanii. All three species can be found in the mouth, skin or gut
  •  A Multi Drug Resistant bacterium can produce specific metallobeta-lactamases which are resistant to all penicillins and cephalosporins and all beta-lactamase inhibitors such as clavulanic acid and avibactam. These bacteria are also resistant to virtually all other antibiotics, with the exception of colistin
  • If resistance arises to colistin, which it has, then there are no treatments left.
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 Diagram showing bacteria that are resistant to drugs Diagram courtesy of www.knowabouthealth.com showing the difference between non-resistant bacteria and drug resistant bacteria. Non-resistant bacteria multiply, and upon drug treatment, the bacteria die. Drug resistant bacteria multiply as well, but upon drug treatment, the bacteria continue to spread.

A number of authorities globally have spoken about the rapidly-emerging crisis. There is an urgent need to invent new antibiotics, though it may already be too late for this to happen in time and at the scale required. Therefore it is essential that we protect current antibiotics, particularly ‘last line of defence’ drugs, from resistance, and develop ‘Antibiotic Resistance Breakers’ (ARBs) that break the resistance that is sure to emerge.

In particular the charity is focussing on repurposing or repositioning existing drugs.

This involves

  1. taking drugs that are currently used for one indication such as cancer treatment or heart disease and examining them for antibiotic activity
  2. combining two existing antibiotics to see if they can overcome antibiotic resistance or
  3. combining one or more drugs together with the antibiotic to see if the antibiotic resistance can be overcome (Antibiotic Resistance Breakers).

A picture showing how antibiotic resistance breakers work

 The first three of the Charity’s research programmes will focus on Antibiotic Resistance Breakers against five widely used antibiotic classes viz. meropenem, ciprofloxacin, aztreonam, gentamicin, colistin and tigecycline to which resistance in Gram-negative bacteria has developed. Resistance can occur in a number of ways. One of these involves the loss of pores in the bacterial cell wall so that the antibiotic cannot penetrate the bacteria. If new pores could be created by the ARB then resistance might be overcome (see football analogy diagram)

 The Programmes

Research programmes and costs

 Test tube screening studies have been undertaken with pan-resistant Gram-negative antibiotic resistant bacteria. As these bacteria are hazardous, handling them requires specialist laboratory facilities in the United Kingdom that can handle these antibiotic resistant bacteria.
 Sites of action of gram-negative bacteria

The research programme has been overseen by Dr Lloyd Czaplewski as project manager under the overall control of the Science Committee.

 The project will focus on overcoming resistance to the fluoroquinolone class of antibiotics in the Gram-negative bacteria Escherichia coli, Klebsiella pneumoniaePseudomonas aeroginosa and Acinetobacter baumanni. The test tube studies will take the resistant bacteria and expose them to fluoroquinolone and another drug(s). The latter will be drawn from any drug that has been approved for any human disease ever.

The research programme will be overseen by a project manager under the overall control of STAC.

 This project will focus on overcoming resistance to colistin in the Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. The test tube studies will take the resistant bacteria and expose them to colistin and another drug(s). The latter drugs will be drawn from any drug that has been approved for any human disease ever.

The research programme will be overseen by a project manager under the overall control of STAC.

This project will focus on finding a new antibiotic from a chemical compound library, natural products or any other source. Gram-negative bacteria will be the target species and the library will either be obtained from commercial sources, provided by a pharmaceutical company, university or any other source of interesting compounds.

As this programme will examine novel compounds not hitherto used as drugs for any therapeutic area, by its nature it will be more expensive and take a longer time to complete than Projects 1-3.

This project will focus on finding a new antibiotic from a chemical compound library, natural products or any other source.. The focus of this project will be different from Project 4, either by examining a different library or using alternative screening systems and / or endpoints. Gram-negative bacteria will be the target species and the library will either be obtained from commercial sources, provided by a pharmaceutical company, university or any other source of interesting compounds.

As this programme will examine novel compounds not hitherto used as drugs for any therapeutic area, by its nature it will be more expensive and take a longer time to complete than Projects 1-3.