Skip to 0 minutes and 6 secondsThere is an urgent need for new generations of antibacterial agents as antibiotic-resistant bacteria threaten everyone's health. In the face of increasing antibiotic resistance, we need to better understand the mechanisms of infectious disease. This includes a comprehensive understanding of antibiotic resistance, and a renewed commitment to discovering novel antimicrobial molecules and therapies. Both natural and synthetic organic compounds are likely to remain important sources for new antibiotics - we will explore potentially significant new approaches and strategies for breakthrough molecules. Phage therapy was studied extensively in Russia during the Cold War. The course of treatment involves the isolation
Skip to 0 minutes and 52 secondsof thousands of bacteriophage species: viruses that infect and replicate bacteria. A sample of the infectious bacteria is taken from the patient and tested against available viruses. Where a virus shows bacteriostatic (stops the growth of bacteria) or bactericidal (it kills bacteria) properties against this specific strain of bacteria the virus is allowed to replicate before being administered to the patient. The bacteriophages injected are specific to bacterial infection. So, beneficial bacteria, often found in the human gut, are not eliminated, as can occur when broad-spectrum antibiotics are used. Despite the potential to overcome antibiotic resistance phage therapy is not currently legalised in most countries. There is reluctance from pharmaceutical companies to invest in the virus 'catalogues'.
Skip to 1 minute and 46 secondsRecently, however, pharmaceutical research has turned to examining natural microorganisms, which are 'uncultivatable' under laboratory conditions, that is to say bacterial or fungal colonies that will not grow in an artificial environment. Currently the isolation chip, or iChip, is being trialled for its potential uses in isolating and developing colonies in situ. That is to say in their natural, external habitat. A sample of cells are collected and placed into a liquid suspension. The sterilized iChip is then passed though the suspension and 'captures' approximately 384 cells, each confined to their own diffusion chamber. The iChip is returned to the site from which the cell samples were originally taken.
Skip to 2 minutes and 36 secondsThis allows the cells within to access the nutrients that they would naturally receive as these diffuse into the iChip. The initial results from screening uncultured bacteria, collected in-situ, has been favourable. A recent study identified a potentially powerful new antibiotic. Teixobactin was found to be extremely effective against gram-positive bacteria, including some strains that already showed a wide diversity of drug resistance. However, teixobactin appeared to be ineffective against the majority of gram-negative bacteria. This can be partly attributed to its mode of action, which targets lipid II, a precursor required for the construction of peptidoglycan cell walls. Gram-positive bacteria possess thick peptidoglycan layers that act as their cell wall; meaning teixobactin can directly interact with them.
Skip to 3 minutes and 35 secondsThis mode of action means that random mutations to specific binding proteins do not inhibit the action of teixobactin, as can occur between beta-lactams and their binding proteins. Though teixobactin still has many clinical trials to undertake in order to ensure it is safe for human consumption there are high hopes that it can soon be added to our antibacterial arsenal. With researchers from four different countries researching teixobactin and the European Union contributing £4.2 million towards a new study on bacteriophages (to treat infections on skin burn sites) there is a definitive shift towards expanding our knowledge and understanding of the microbial world.
New directions of antibiotics
In a world without antibiotics, transplant surgery becomes virtually impossible, pneumonia (once again) becomes a mass-killer, gonorrhea would be hard to treat and tuberculosis becomes incurable. In 2014, the UK Government’s Review on Antimicrobial Resistance warned that failure to tackle drug-resistant infections could lead to at least 10 million extra deaths a year by 2050 and end up costing the global economy up to £70 trillion.
With the world’s cabinet of useful antibiotics almost bare, we have seen that researchers are rushing to discover replacements using natural resources. Some researchers are trying to mine the untapped potential of soil bacteria, devising new kinds of growth chambers that might allow unstudied species to thrive in the lab. Others are genetically engineering microbes to produce novel compounds that could be useful for making medicines. Still others are scavenging the native antibiotics in ocean life, fungi and insects.
Until we have replacements, it is important to keep bacteria at bay. Hygiene is an obvious weapon. Better cleaning, hand gels and stern warnings to staff and public alike have helped reduce infection rates in hospitals.
There is also a real need to conserve those antibiotics we have, including those used in livestock and fish farming (veterinary use of antibiotics outstrips human use globally). Human health may be at risk from antibiotic resistant infections being passed on via the food chain, from direct contact with infected animals and from farm waste. For example, biologists at York have found that only trace concentrations of antibiotic, such as those found in sewage outfalls, are enough to enable bacteria to keep antibiotic resistance. In the USA more than 70% of antibiotics that are medically important for humans are used in animals.
The finite lifetime of our current arsenal of antibiotics has been likened to the world’s finite reserves of oil. With the problems of energy usage, carbon trading was introduced to try to conserve oil and also reduce its pollutant effects. If such a worldwide tax was introduced for antibiotics the proceeds could fund future research and development.
But should we tax life-saving medicines, especially in poor countries?
Globally, should we reduce antibiotic use in food production, in livestock and fish, and introduce restrictions on the use of antibiotics in these animals that are important for humans?
© University of York