April 29, 2014

The bacteriophages of tuberculosis

I’ve written previously about bacteriophages, the viruses that infect bacteria, and I studied them for my first lab project. So I was pretty excited by a lovely little pearl in PLoS Pathogens last month discussing mycobacteriophages; the viruses that specifically attack mycobacteria.

By S.E. Gould

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I've written previously about bacteriophages, the viruses that infect bacteria, and I studied them for my first lab project. So I was pretty excited by a lovely little pearl in PLoS Pathogens last month discussing mycobacteriophages; the viruses that specifically attack mycobacteria. Mycobacteria are a group of bacteria that contain some highly dangerous human pathogens, including the agents of tuberculosis: Mycobacterium tuberculosis.

M. tuberculosis are particularly slow at reproducing, sometimes taking as much as 24 hours before splitting in half. This is chronically slow for a bacteria considering E. coli manages it in about 20 minutes. Bacteriophages are therefore very useful for increasing the genetic diversity of the bacterial population by carrying around genes between individual bacterium. Phages have also been exploited by researchers who find it useful to be able to insert new genes into bacteria making them easier to genetically manipulate and study.

There is potential for bacteriophages to act as therapeutic agents, particularly those that infect the bacteria and destroy it. This is particularly relevant for tuberculosis which has high levels of antibiotic resistance. Unfortunately most mycobacteriophages don't kill their bacterial hosts, instead they just insert their DNA into the bacterial genome becoming part of it.The other problem is that during established infection M. tuberculosis exists within human cells surrounded by an inflammatory structure called a granuloma. This makes it difficult for both phages and antibiotics to reach the bacteria.

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One option the authors do propose is that a cocktail of 3-6 bactericidal phages might be used to prevent the spread of infection, attacking the bacteria before they have a chance to settle down in a persistent infection within the human host. They suggest that if someone is diagnosed with tuberculosis anyone in close contact with them (such as family and co-workers) could take a phage inhaler to remove tuberculosis bacteria from the throat and upper lungs before an infection can be established. The added benefit of phages is that they are specific for the bacteria they infect and therefore will not affect the natural bacterial flora in the respiratory tract.

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Reference 1; Hatfull GF (2014) Mycobacteriophages: Windows into Tuberculosis. PLoS Pathog 10(3): e1003953. doi:10.1371/journal.ppat.1003953

Reference 2: Gross L (2006) A Novel Phage Protein Mediates the Virus's Removal from Bacterial Chromosomes. PLoS Biol 4(6): e213. doi:10.1371/journal.pbio.0040213

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