MicrobiologyBytes Weekly – timebombs, smarter antibiotic use and bacteriophages you've never even heard of

Alan Cann Welcome to the first edition of the new format MicrobiologyBytes!

In this week’s edition:

  1. Today is World Polio Day
  2. Antibiotics – have we got it all wrong?
  3. Unexploded device? The vCJD timebomb
  4. How science works
  5. The wonderful world of archaeal viruses
Today (October 24th) is World Polio Day 

In support of this event the UK Society for General Microbiology has published a useful document describing the fight against this disease – past, present and future – and the lessons it hold for other infections (free, and very useful for teachers and students).

Poliovirus
When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load 

Cancer is a difficult disease to treat, but great advances have been made in the past few decades, mostly coming from using drugs in combination rather than one at a time. Exactly the same drug combination approach works for HIV infection, although sadly it doesn’t provide a cure. As it becomes harder and harder to treat bacterial infections with the few remaining antibiotics which are still effective, we need similarly imaginative approaches to therapy. A new paper in PLOS Biology looks at combinations of different drugs that are purposefully used to produce potent therapies. Textbook orthodoxy in medicine and pharmacology states one should hit the pathogen hard with the drug and then prolong the treatment to be certain of clearing it from the host. If the textbooks are correct, a combination of two antibiotics that prevents bacterial growth more than if just one drug were used should provide a better treatment strategy. Testing alternatives like these, however, is difficult to do in vivo or in the clinic, so the authors examined these ideas in laboratory conditions where treatments can be carefully controlled and the optimal combination therapy easily determined by measuring bacterial densities at every moment for each treatment trialled. Studying drug concentrations where antibiotic synergy can be guaranteed, they found that treatment duration was crucial. The most potent combination therapy on day 1 turned out to be the worst of all the therapies we tested by the middle of day 2, and by day 5 it barely inhibited bacterial growth; by contrast, the drugs did continue to impair growth if administered individually. 

When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load: The Smile-Frown Transition. (2013) PLoS Biol 11(4): e1001540.

 

Unexploded device? The vCJD timebomb 

Over at the Principles of Molecular Virology blog, I’m publishing the updated content for the next edition of the book as I research it. Chapter 8 of Principles of Molecular Virology discusses subviral agents – viroids and prions responsible for diseases such as scrapie, BSE and CJD. So many facts about human prion disease remain unknown, but what is clear is that decades after it started, mad cow disease has not gone away – the effects of the outbreak will rumble on for decades to come. New data from the UK show that the previous estimate of the number of vCJD carriers was an underestimate, but what does the future hold for those exposed to BSE-infected food in the 1980s and 1990s?

Principles of Molecular Virology
Molecular structure of the HIV-1 envelope protein 

A group of researchers publishes a structure for the HIV-1 envelope protein complex – the crucial membrane-fusing molecular machine responsible for virus attachment and entry into host cells and which is the sole virus-specific target for neutralizing antibodies (Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer. (2013) PNAS USA 110 (30): 12438-12443). You’d think people would be happy. But not everyone is. “You got it wrong” they say, or “Oh no it isn’t“. “We took you comments into account and we still believe we are right” say the original authors. “Look at this picture of Einstein” says the world’s leading expert in the field. This saga is a great illustration of how science really works and a warning for students and journalists who want to believe that there are simple right/wrong answers to complex questions and that we either know something or we don’t. A great example of how sciences inches closer to the truth one step at a time.

Einstein
The wonderful world of archaeal viruses 

Think you know about bacteriophages? You might be shocked at how much you have to learn. Most microbiologists are obsessed with “true bacteria”, to the virtual exclusion of the Archaea. That prejudice carries over to their viruses. This review [sorry this one requires a subscription – I try to avoid this whenever I can] presents a personal account of research on archaeal viruses and describes many new virus species and families, demonstrating that viruses of Archaea constitute a distinctive part of the virosphere and display structures that are not associated with the other two domains of life, Bacteria and Eukarya. Studies of archaeal viruses provide new perspectives concerning the nature, diversity, and evolution of virus-host interactions. Broaden your outlook – this one is well worth reading.

The wonderful world of archaeal viruses. (2013) Ann Rev Microbiol. 67: 565-585.

Bactriophage STIV2

 

Got any comments or questions about any of these items? Just let me know.

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