I did a post about a week ago, talking about the relationship between the bodies natural (commensal) bacteria and the immune system. I was quite excited therefore to find a paper (reference below) which found a specific protease enzyme that is used by commensal throat bacteria to prevent harmful biofilm formation by Staphylococcus aureus, the bacteria responsible for MRSA.The helpful bacteria in question is Staphylococcus epidermidis which lives naturally in the throat and nasal cavity of humans. When culturing these bacteria along with the Staph aureus it was found that some epidermidis cultures were capable of destroying biofilm formation, by using the protease Esp. The diagram below shows the effects of extracted Esp on colonies of Staphylococcus aureus (image from the reference):
Figures g and j show Gram stains of the colonies, the blue dye has just stained where bacteria are present. The remaining figures show scanning electron micrographs of the colonies taken at two different levels of magnification. For those interested, the scale bar for g,h,j and k is 10um and for i and l is 1um.
To double check that this protein was having an effect within the bacteria knockout mutants were made which removed the gene from Esp from the epidermidis. These bacteria were incapable of destroying Staph aureus growth. Adding a plasmid containing the Esp gene back into the bacteria restored their ability to fight off the Staph aureus which seems fairly conclusive. Furthermore this affect also works with VRSA and MRSA; Staph aureus which are resistant to antibiotics.
Below is a diagram of the effect of actual epidermidis bacteria on Staph aureus colonies (image from the reference).
These are nasal swabs taken from volunteers who had Staph aureus infections and were given the commensal epidermidis strains to try and clear them. It can be seen that the number of staph aureus is decreasing, although some bacteria are still present after five days of treatment. That might not necessarily be a bad thing as it allows the immune system to kick in with a response, and make antibodies ready for the next potential attack.There are several exciting things that come out of this. Firstly the use of purified Esp as a defence against MRSA biofilms has the potential to be of major importance, although there may be clinical reasons why it's not such a good idea to spray proteases all over the inside of someones nose! From a less medically-useful perspective it's a wonderful example of bacterial-colony interaction. The kind of struggle for survival that happens inside your nose is occurring for bacteria everywhere; in soil, in the water, in the air, and even in humans.
From the Staph epidermidis point of view your nasal cavity is just a great place to live (warm, safe, lots of nutrients) and it's not going to give up that kind of living environment without a fight!
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Iwase, T., Uehara, Y., Shinji, H., Tajima, A., Seo, H., Takada, K., Agata, T., & Mizunoe, Y. (2010). Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization Nature, 465 (7296), 346-349 DOI: 10.1038/nature09074
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8 comments:
It's a pretty cool find huh. We wrote it up a little while back. I have been wondering whether it would be possible to make some kind of respiratory probiotic including Esp and/or Staph ep to elict passive protection.
Also I dont remember seeing it but did they test Esp against other species? If effective at inhibiting Strep pneumo growth then there is the potential for this to be HUGE!
Thanks for the summary.
@disease: I don't think they looked at the effect on any other species, but you're right, it would be amazing if the Esp (or even the strep!) had an effect on Pneumo, or even psedomonas aeruginosa or something.
I'm surprised there's so little work on respiratory probiotics actually, given there's so much industrial and commercial interest in gut microbials.
respiratory, skin, even underarm probiotics - millions of people would benefit from those. Commercial products are available, but I don't know of any studies proving the benefits (examples: probiotic mouthwash or probiotic skin cream). See also this proposal: Developing Methylophilus methylotrophus probiotic to help TMAU sufferers.
I know that for streptococcus salivarius produces a lantibiotic that eliminates other flora. Someone has even marketed it as a treatment for halitosis.
http://www.breezecare.com/probiotics/blisexplained.html
@aurametrix and @fax: thanks for the extra info! It really is interesting to know that some companies are actually picking up on this. Whether academic scientists like it or not industry is good at pouring money into research areas :)
Another wonderful post!
I suppose there could be a potential problem with using Staphylococcus epidermidis as a respiratory probiotic. Like many commensal species, S. epidermidis is an opportunistic pathogen. It usually sits happily on the skin or in the nasopharynx, but it causes problems when it gets in the wrong place or if host immunity is compromised.
S. epidermidis pneumonia has been documented in immunocompromised patients, but even in immunocompetent patients, S. epidermidis causes serious infections. Because it is so abundant and has a tendency to form biofilms on surfaces, it is responsible for many infections associated with prosthetic implants, such as urinary catheter infections, joint replacement infections, and endocarditis.
Interestingly, nosocomial S. epidermiditis strains have become increasingly difficult to treat, because repeated exposure to antibiotics have triggered them to evolve resistance.
The human body is a delicate ecosystem!
@HHM I thought their might be issues with opportunistic invasions, I'm guessing that this is more likely to happen in the respiratory tract that in the stomach, especially due to biofilm formation.
There is a paper which I might get round to at some point about the build-up of antibiotic resistance in commensal strains. This can act as a large pool of resistance, which becomes a major problem in the case of either opportunistic infection or conjugation.
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