Defeating the Superbugs (Horizon)

Research led by Roy Kishony uses a

Research led by Roy Kishony uses a “morbidostat” to deliberately develop antibiotic resistant bacteria

Broadcaster: BBC 2

Year: 2012

Genre: Documentary

URL: http://bobnational.net/record/293666

Review by Josh Sutton

Antibiotic resistance in bacteria is currently one of the largest problems facing modern medicine. The rise in cases of multiple drug resistance tuberculosis (MDR-TB) and methicillin-resistant Staphylococcus aureus (MRSA) are only the best-known examples of a wider issue. In this Horizon documentary from 2012, the increasing threat of antibiotic resistance is covered, as well as reflections on the new treatments and drugs that scientists are developing to combat the growing resistance threat.

The importance of antibiotic resistance is immediately highlighted in the programme, with the story of a soldier put into a critical condition after his legs were blown off. His perilous state was actually due to an infection with antibiotic-resistant bacteria he went on to develop: MRSA, Pseudomonas aeruginosa and Acinetobacter baumannii. This infection could only be treated with antibiotics of last resort, which were toxic to both the bacteria and the soldier himself.

The potential spread of MDR-TB is used to explain what would happen if we did not develop any new antibiotics (http://bobnational.net/record/294123). The high population density in our cities allows easy spread of drug resistant strains. Previously a cocktail of antibiotics could treat TB, however there have been cases of totally drug resistant in other countries, and with increasing globalisation the risk of these more dangerous strains spreading is a potential threat. This clip (2:41) could be used as the beginning of a discussion on the impacts of antibiotic resistance, and the methods that could be used to help combat resistance.

One important aspect of the battle against antibiotic resistance is the need to better understand how mutations lead to resistance development. In Harvard University, experiments have been undertaken to deliberately develop resistance in E. coli (http://bobnational.net/record/294124).  Low concentrations of antibiotic are dripped into the bacterial cultures, using a morbidostat, allowing some of the bacteria to survive due to beneficial mutations. The antibiotic concentration is increased and further mutations allow more bacteria to survive. In this way mechanisms for resistance development can be studied. This clip (6:20) would be useful clip to discuss the mechanism of such evolution, as well as experimental design. The notion of deliberately generating “superbugs” also raises ethical questions.

In another informative section, the programme follows the work of Lance Price, who uses bacterial genomic analysis to track the epidemiology of antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). In a six minute section (http://bobnational.net/record/294126) we see how Price tracked down the spread of MRSA and how it evolved. It turned out that a key step in development of drug resistance occurred in pigs. This highlights issues relating to widespread use of antibiotics in farming. Although the practice is banned in the EU (since 2006), in many parts of the world farmers routinely add antibiotics to animal feed to increase yield. As Price notes, “The crown jewels of modern medicine are being used like cheap production tools“. Global travel allows these new strains to spread; the MRSA that Price was tracking has already turned up in over 18 countries. He now promotes agricultural practice that avoid this overuse of antibiotics. This section can be used as part of a discussion on ethics; on the one hand using antibiotics in the feed is contributing to antibiotic resistance, but on the other hand it is helping to increase food yield and for farmers in poorer parts of the world that may help them to make more money to survive, as well as produce more food to feed the hungry.

The documentary moves on to discuss alternatives to antibiotics. The first of these is the use of bacteriophage, viruses that specifically target bacteria (see http://bobnational.net/record/294127, again about 6 mins). David Harper collects bacteriophage (phage) from sewage plants. He wants to use these phage to kill pathogenic bacteria. Specific phage attack particular bacterial species. The advantage of phage over antibiotics is that they can evolve along with the target bacteria, meaning that resistance is harder to develop. This documentary suggests some of the challenges in finding suitable bacteriophage for treatment, but does not cover that fact many bacteriophage have a lysogenic lifestyle, so are not suitable for treatments. [For more information about the potential use of phages as medicine listen to this clip from the BBC Radio 4 programme Inside Health, featuring an interview with Professor Martha Clokie (http://bobnational.net/record/279344)].

The other alternative is involves an interruption to bacterial communication (quorum sensing). Professor Bonnie Bassler suggest we can achieve behaviour modification rather than killing them. How can it be that microbes so small can kill us? Because they don’t act individually. If we could stop this process, we might be protected. In this 10 minute clip (http://bobnational.net/record/294128) Prof Bassler shows there are parallels between bacterial collaboration in squid so that they make just enough light to help camouflage the host squid. The concentration of molecules secreted is used to determine the number of bacteria present and they only act when there is an appropriate number of individuals present. It seems all bacteria can communicate using these quorum sensing molecules. Bassler’s team have developed some antagonist molecules which interrupt the communication by binding to receptors. They have also developed molecules to bind to and sequester the signalling molecules to prevent the communication.

Both this clip and the clip discussing phages could be used as an introduction to the different approaches people are taking to find alternative drug treatments. [More information on quorum sensing can be found in this TED talk by Bonnie Bassler].

Overall this is an excellent documentary that covers many aspects of an important topic in great detail. It would serve as a good source of information for someone interested in the future antibiotics and antibiotic alternatives.

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