Shortly after Félix d’Herelle discovered viruses that infect bacteria in 1917 (also found in 1915 by Twort), he recognized their therapeutic potential for treating infections. The discovery of penicillin in 1928 began the golden age of antibiotics, which pushed aside progress in treating infections with bacteriophages. With the advent of widespread antimicrobial resistance, development of phages as therapeutic drugs gained momentum. Three recent examples serve to illustrate the untapped potential of these viruses for treating human bacterial infections.
antibiotic resistance
Bacteriophage superspreaders
Bacteriophages are the most abundant biological entities on Earth. There are 1031 of them on the planet, and they infect 1023 to 1025 bacteria every second. That’s a lot of lysis, and it leads to the release of huge quantities of DNA that can be taken up by other organisms, leading to new traits. It seems that some bacteriophages are very, very good at releasing intact DNA, and they have been called superspreaders (link to paper).
In a very simple experiment, E. coli cells carrying a plasmid encoding ampicillin resistance were infected with the well studied phages T4 and T7 and also with a collection of 20 phages isolated from soil, water, and feces in Miami and Washington DC. After the cells lysed, DNA was extracted from the culture medium and introduced into antibiotic sensitive E. coli. Two phages, called SUSP1 and SUSP2, were thousands of times better at releasing plasmid DNA that readily conferred antibiotic resistance. These phages are superspreaders.
Superspreader phages can promote transformation by different plasmids, so their unique talent is not sequence specific. When these phages lyse cells, intact plasmid DNA is released. In contrast, phage T4 infection leads to degradation of plasmid DNA in the host cell. Superspreader phages lack genes encoding known  endonucleases – enzymes that degrade DNA, possibly explaining why plasmids are not degraded during infection. Other phages that lack such endonucleases, including mutants of lambda and T4, also promote plasmid mediated transformation.
Phages SUP1 and SUP2 don’t just spread plasmids to laboratory strains like E. coli. When crude mixtures of soil bacteria from Wyoming and Maryland were mixed with SUP1 and SUP2 lysates from E. coli, antibiotic resistance was readily transferred. One of the main recipients of plasmid DNA is a member of the Bacillus genus of soil bacteria, showing that superspreaders can move DNA into hosts of a species other than the one they can infect.
With so many bacteriophages on the planet, it is likely that there are many other superspreaders like SUP1 and SUP2 out there. The implication is that massive amounts of intact plasmid DNAs are being released every second. These DNAs can be readily taken up into other bacteria, leading to new phenotypes such as antibiotic resistance, altered host range, virulence, the ability to colonize new niches, and much more.
You might wonder if all that plasmid DNA, floating in the environment, can also enter eukaryotic cells – and the answer is yes. No wonder eukaryotes didn’t invent anything.
TWiM 53: Live in Manchester
On episode #53 of the science show This Week in Microbiology, Vincent, Laura, David, Kalin and Paul get together at the Society for General Microbiology meeting in Manchester, England to talk about next-generation approaches to antimicrobial therapy.
You can find the audio for TWiM #53, along with show notes, at microbeworld.org/twim. Watch video of the episode below.
Behind the scenes in Manchester
Live from the Society for General Microbiology Conference in Manchester, UK
MicrobeWorld and the Society for General Microbiology (UK) to live stream two events from their Spring Conference 2013 in Manchester, England, March 25-28.
Peter Wildy Prize for Microbiology Education
Monday, March 25, 2013 17:20 GMT (1:20 PM EST | 10:20 AM PST)Â Â
David Bhella, Ph.D., will be accepting the Peter Wildy Prize for Microbiology Education, awarded annually by the Society for General Microbiology for an outstanding contribution to microbiology education. Bhella’s acceptance speech will be live streamed at 17:20 GMT (1:20 PM EST | 10:20 AM PST). Vincent Racaniello was awarded the Wildy Prize in 2012.
This Week in Microbiology
Wednesday, March 27, 2013 15:30 GMT (11:30 AM EST | 8:30 AM PST)Â
Join Vincent Racaniello and co-host Laura Piddock, Ph.D., with guests Paul Williams, Ph.D., Kalin Vetsigian, Ph.D., and David Harper, Ph.D., for a live-streaming episode of This Week in Microbiology. The live stream starts at 15:30 PM GMT (11:30 AM EST | 8:30 AM PST) and you can watch it below. If you have any questions for Vincent or his guests during the broadcast you can tweet your question using the #sgmman hash tag or type it into the chat function of the video player.
If you live elsewhere in the world, please use www.everytimezone.com, to calculate when the live streams will start in your area.