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Tiny RNA fragments control bacterial infections

The views expressed are those of the author and are not necessarily those of Scientific American.

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There is more than one type of genetic material within the cell. As well as DNA, which stores the code for making cellular protiens, there is also RNA, which contains similar snatches of code but is less stable and more mobile than DNA. If DNA is a library of books which are not allowed to be removed, then RNA is little buts of paper containing copies of pages that are spread around for people to read.

The differences between RNA (left) and DNA (right). RNA is also found as a double helix, a triple helix and a strange looped thing. Image from wikimedia commons, credit link below.

Given its power to act as an intermediary between DNA and protiens, which are two of the most important macromolecules within the cell, RNA has a huge number of jobs to do. One of those jobs is to regulate which parts of the DNA are making proteins. Not all of the DNA in the cell is being used all the time, and small pieces of RNA have the ability to show the cell which parts of the DNA need to be working at any one time.

In the case of the bacteria Streptococcus pneumoniae, the small RNAs can turn on the parts of the DNA required to make the bacteria virulent. It seems that the bacteria uses very specific RNA fragments to turn on different genes at different stages in its virulence cycle. At each stage, a specific set of small RNAs will be produced in order to control gene expression. A recent paper from PLoS Pathogens (reference below) carried out three sets of experiments to show this. Firstly, they sequenced the entire genome of the Streptococcus in order to find the sections that looked similar to other bacterial small RNAs. Once identified (they found around 89!) they specifically removed the ability of the cells to make the some of the small RNAs to see the effect that had on bacterial virulence. Finally, they looked for the targets of these RNAs, to find out which parts of the DNA expression they were actually affecting.

Streptococcus pneumoniae from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #262. Credit link below.

To explore the effect of removing the small RNA sections they looked at a measurement called the “competitive index” which involved infecting mice with both the wild-type and mutated bacteria (bacteria without the small RNAs) and seeing how well they compared when in competition with each other. A competitive index of one means that equal amounts of wild-type and mutant bacteria were found, less than one means that more wild-type bacteria were found and greater than one means that more of the mutated bacteria were found. As expected, in almost all individual cases the mutants performed worse than the wild-type in infection, some performing significantly badly.

Results from reference 1 below

The graph above shows the effect of removing certain sRNA from bacteria infecting the blood. Each point represents a single individual, with the lines showing the average of the strain. The scale is logarithmic, which means that while strain F5 was around 5 times worse than the wild-type on average, strain R12 was over 100 times worse. What’s also interesting is that one individual with the F5 mutation performed better than the wild type, although two of them also performed much, much worse. The paper explored the fate of mutations on virulence in the nose/throat area and the lung, with mutants performing worse in all cases.

Finding the target sites of the small RNAs was more complex, as each one appeared to both up-regulate (turn on the production) and down-regulate a large number of proteins. To explore this, the researchers carried out Northern Blots, which leave a stain for every protein produced inside the cell, for both the mutants and the wild type and then compared the similarities and differences. The graph below shows the huge differences in proteins controlled, and suggests that each small RNA has a large number of effects within the cell, controlling a range of responses including DNA repair, synthesis of nucleotides, and virulence.

The number of upregulated and downregulated proteins found for each mutation. Image from the reference below

Using RNA to send important messages to the genome is an advantageous strategy for bacteria, as it uses less energy than creating proteins to do the job, and requires less DNA to store the information. RNAs can either be very specific, or focus on multiple targets, allowing them to have very defined roles in controlling large genetic changes, such as the onset of bacterial virulence. The main task the researchers have now, is to work out the precise function of all these RNAs, and which genes they tweak to create the pathogenic bacterial cell.

Credit link for image 1

Credit link for image 2 (Link to the CDCs Public Health Image Library)

Reference 1: Mann B, van Opijnen T, Wang J, Obert C, Wang YD, Carter R, McGoldrick DJ, Ridout G, Camilli A, Tuomanen EI, & Rosch JW (2012). Control of Virulence by Small RNAs in Streptococcus pneumoniae. PLoS pathogens, 8 (7) PMID: 22807675

S.E. Gould About the Author: A biochemist with a love of microbiology, the Lab Rat enjoys exploring, reading about and writing about bacteria. Having finally managed to tear herself away from university, she now works for a small company in Cambridge where she turns data into manageable words and awesome graphs. Follow on Twitter @labratting.

The views expressed are those of the author and are not necessarily those of Scientific American.

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  1. 1. Ignisha 8:20 pm 08/26/2012

    Can the findings of this study lead to the development of medicine that halt the bacteria from developing into virulent stage?

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  2. 2. WRR Munro 9:52 pm 08/26/2012

    I’d imagine the answer is that it will be very hard to achieve in a way that’s useful to reduce disease. They’ve already created less virulent bacteria, in that they’re less competitive with their wild cousins – which is the problem. The tricky bit will be to create a variant that can out-compete the wild-types but be do less damage to humans.

    If they could create staphylococcus aureus which safely out-competes with MRSA, that would be a major boon, though.

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  3. 3. S.E. Gould in reply to S.E. Gould 3:25 am 08/27/2012

    I’m not sure this study has a direct clinical application, and I’m certainly not keen on the idea of using less-virulent bacteria to outcompete the wild ones – too much chance of DNA sharing and mutation! Understanding how bacterial virulence works is important though, and you never know which particular bit of research might reveal a new area for clinical exploration.

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  4. 4. vapur 7:54 am 08/27/2012

    quotes, “If DNA is a library of books which are not allowed to be removed…”

    But they books can be rewritten? Bad analogy!

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  5. 5. S.E. Gould in reply to S.E. Gould 8:26 am 08/27/2012

    It was not an analogy to describe every facet of the behaviour of DNA, it was just a quick explanation of the differences between DNA and RNA. The point is that the DNA stays more-or-less where it is in the cell, while the RNA zips around all over the cytoplasm as well as interacting with the DNA.

    The only real analogy that works is: “DNA is like DNA” because to be honest there is nothing else that behaves in exactly the same way as DNA. It’s a wonderfully unique molecule.

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  6. 6. aidel 11:38 am 08/27/2012

    Is a similar mechanism at work with viruses?

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  7. 7. S.E. Gould in reply to S.E. Gould 4:23 am 09/4/2012

    @aidel: Sorry it’s taken me so long to reply to this! Virus’s are in a slightly different position as the actual virus just contains a small bit of genetic material inside a protein coat. It doesn’t start expressing that material until it gets inside a host cell. Once they are in the host cell though, they do indeed use small pieces of RNA for expression – some from their own DNA and some from the host DNA.

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  8. 8. dean12345 7:47 am 02/11/2015

    Does antibiotics medicine contains RNA .

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