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 Brief Description of Biofilm Infections

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Martha Foster



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PostSubject: Brief Description of Biofilm Infections   Wed Jul 13, 2016 5:28 am

This article will be a brief description of the formation of biofilms and why they may be involved in bacterial infections of the urinary tract.  Biofilms have been mentioned  on this forum but not in depth and not accompanied by a detailed description.  This will be a more in depth description and hopefully will stimulate other comments on this kind of infection.

Here are a few facts about biofilms:  Microbes do not normally live as free-flotating, planktonic organisms in enriched media on agar plates.  They naturally prefer life on the edge, in protected communities nestled within biofilm.  Biofilm is a gathering of sessile microoganisms encased by a self-generated hydrated matrix, strongly attached to a surface.  Bacterial and fungi living within biofilm differ substantially from their free-living planktonic fellows.  Genes mediating adhesion, growth, and motility are downregulated, while those mediating exopolysaccharide synthesis and antibiotic resistance are upregulated.  Microbes within biofilms communicate with each other, display metabolic specialization, and even sometimes appear to undergo apoptotoic programmed cell death so as to benefit the greater biofilm community.  Biofilms are ubiquitous in nature, including the human body.

Biofilms increase microbial survival.  Biofilm shields microbes from humoral and cell-mediated immune responses.  Resistance to antimicrobial agents is intrinsic to the biofilm mode of life.  Depending on the species and antibiotic, biofilm phenotypes are from 10 to over 1000 times more resistant to antibiotics than their planktonic comrades.  The mechanisms of antibiotic resistance are not well-understood.  Reduced antimicrobial diffusion into biofilms is one means.  There are other proposed mechanisms  and all of these combine to provide biofilm communities with a multifaceted defense system.

I would like to give credit for the information above to Dr. Stephen Olmstead in the USA. Most of the information is quoted from a longer article he wrote and that was published in The Townsend Letter.  There are many other doctors and researchers who are finding biofilms in infections in many areas of the body, but we are most interested in this forum about possible biofilm infections in the urinary tract.  There is a great deal of information that has been published in journals all over the world.  Below are some of the articles I have found.  And please watch this video on YouTube, featuring Dr. William Costerton, describing a short history of the discovery of biofilms and predictions for the future treatment.
https://www.youtube.com/watch?v=aXFl_GGW7x8

Interesting articles are included below:
 
http://cid.oxfordjournals.org/content/early/2014/10/03/cid.ciu634.full.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617679/
https://www.ucl.ac.uk/infection-immunity/research/tabs/biofilm

More posts are welcome to add to the above description of biofilm infections which could add another dimension to the cause of IC/LUTS.

Martha Foster
Virginia, USA
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Andi2016

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PostSubject: Re: Brief Description of Biofilm Infections   Sat Jul 16, 2016 11:23 am

Thanks for sharing this, Martha Foster.  Scott Hultgren's team has been talking about Uropathogenic
Escherichia coli (UPEC) and intracellular bacterial communities (IBC) as being a 'biofilm-like' state for some time now.  Since they are saying this is responsible for recurrent UTIs,  I don't understand why it's considered such a far stretch for it to be linked to IC/PBS.   Here's a link to Hultgren's lab that refers to biofilm:  
http://hultgrenlab.wustl.edu/research/bacterial-community-interactions-biofilms-and-microbiome/


I was interested in your link to the UCL Biofilm Centre and seeing Professor James Malone-Lee's name listed under their contributing scientists and clinicians.  His team has also referred to certain uropathogens having the ability to form intracellular and extracellular biofilm.

I need to find where I read it, but I'm sure one of Hultgren's papers states that UPEC can form biofilm very early on in an infection - something like 6 hours in.  And once it forms, it produces little pocket reservoirs inside the bladder where bacteria can hide, survive and continue to thrive unheeded.    If this is the case, how can we rely on standard agar testing to rule out a UTI?   Especially when those tests are designed for acute UTIs that involve planktonic bacteria in the urine.

This is written to explain biofilm involvement in chronic wound infections  - but it's a very good explanation to understanding biofilm: http://www.woundsinternational.com/media/issues/288/files/content_8851.pdf

This is also a really good youtube clip about biofilm - and infections in the urinary tract is mentioned:
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Andi2016

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PostSubject: Re: Brief Description of Biofilm Infections   Sat Jul 16, 2016 5:07 pm

I see urology is on the agenda for the Allegheny Health Network Center for Excellence in Biofilm Research (AHN CEBR) based in Pittsburgh.

"Currently researchers are conducting pioneering studies in the specialties of orthopaedics, cardiology, oncology, obstetrics, and urology. The goal of these collaborations is to better understand the role bacteria, particularly biofilms, play in complex clinical situations."

https://www.ahn.org/allegheny-health-network-research/our-research-institutes/biofilm-research
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Susa2016



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PostSubject: Re: Brief Description of Biofilm Infections   Sat Jul 16, 2016 5:58 pm

I'd just like to add my two pennies worth to this thread:

Sara Soto in a paper entitled "The Importance of biofilms in urinary tract infections" notes the following

"According to the NIH, biofilm forming bacteria involved up to 80% of all infections, with urology being one of the main fields in which biofilm can become a serious problem. Biofilm can be found in the urothelium, prostate stones, and implanted foreign bodies".

"Several studies observed that most of isolates collected from patients with relapse infections were biofilm producers “in vitro”. Relapse by uropathogenic E. coli (UPEC) has been related to the ability of pathogenic strains to form biofilm. In these cases, biofilm production may be the key determinant for the persistence of UPEC in the vaginal reservoir, the bladder epithelial cells, or both.  Thus, in a study carried out in the Hospital Clinic of Barcelona, 43 ambulatory female patients ≥ 18 years of age were included following an index episode of cystitis or pyelonephritis, and they were clinically followed for at least 6 months, collecting urine cultures every month. Eighty E. coli strains were collected, 27 causing relapses and 53 causing reinfections. Among them, 74% and 42% were “in vitro” biofilm producers, respectively, demonstrating a relationship between persistence, relapse, and biofilm formation".
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summerly



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PostSubject: Re: Brief Description of Biofilm Infections   Mon Jul 18, 2016 11:37 am

Thanks everyone for the interesting articles. Aren't bacteria amazing! I don't know about everyone else, but it seems to me that if bacteria can form biofilm communities that make them extremely difficult to culture and even harder to get rid of, and they can also form these biofilms within cells, then how on earth can they say that infection is not involved in ICBPS? Would a bladder flare relate to when bacteria in biofilms are in the spore/re-seeding part of their lifecyle?

If it's okay, I thought I'd add a few more to the list which I found interesting.

According to this article -
http://www.ncbi.nlm.nih.gov/pubmed/11463434- “even sensitive bacteria that do not have a known genetic basis for resistance can have a profoundly reduced susceptibility when they form a biofilm” and bacteria communicate through an “exchange of chemical signals between cells in a process known as quorum sensing.”

And here is a fantastic Ted talk on quorum sensing -
https://www.ted.com/talks/bonnie_bassler_on_how_bacteria_communicate?language=en

"E. coli has also been reported to be able to form intracellular biofilm-like aggregates inside bladder cells making the bacteria hard to reach by both host defence mechanisms and antibiotics" (Anderson et al., 2003) see below, from this link - http://www.ncbi.nlm.nih.gov/pubmed/17526829

Anderson, G. G., Palermo, J. J., Schilling, J. D., Roth, R., Heuser, J. & Hultgren, S. J. (2003). Intracellular bacterial biofilm-like pods in urinary tract infections. Science 301, 105–107.

And a pdf on biofilms in wound care but it explains the biofilm lifecycle in a way that is easy (for me at least) to understand.
https://www.google.com.au/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwjFq-eMg_zNAhXEkpQKHXybCCEQFggdMAA&url=http%3A%2F%2Fwww.woundsinternational.com%2Fmedia%2Fissues%2F288%2Ffiles%2Fcontent_8851.pdf&usg=AFQjCNE1mEoh9VdHCnssNuOuFSSCDcIF7g&cad=rja

News article on enzymes to break up biofilms.
https://www.sciencenews.org/article/scientists-find-way-break-through-bad-bacteria%E2%80%99s-defenses

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Andi2016

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PostSubject: Re: Brief Description of Biofilm Infections   Mon Jul 18, 2016 3:09 pm

You make a very good point, Summerly. There seem to be a few progressive research groups in the US and the UK that are making really interesting findings in terms of biofilm in the urinary tract and bacterial behaviour. Based on these new understandings, how can an infectious cause be ruled out? Prof Marshall commented he was searching for a way to absolutely exclude an infectious cause for IC/PBS. I wonder how/if the possibility of biofilm involvement can be ruled out? There is such strong proof out there linking intracellular and extracellular biofilm to recurrent UTIs.

I've watched the Bill Costerton interview (posted above by Martha Foster) so many times. When looking at nature, he discovered 99.9999 percent of bacteria was stuck on surfaces in biofilms and barely any free floating bacteria was found in the actual water. He says biofilm won't show up using cultures (and cultures are used in labs all over the world to diagnose UTIs - or in our case, to rule them out). The culturing process used in labs is based on Koch's methods, which were designed to diagnose acute bacteria infections, and these cultures are just not good at picking-up biofilm infections. According to Bill Costerton, microbiologists stopped using cultures for analysing soil and water populations back in the late 1970s-early 1980s, but they are still being used right throughout medicine.

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Andi2016

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PostSubject: Re: Brief Description of Biofilm Infections   Thu Aug 18, 2016 2:42 pm

You've got to love Bill Costerton's voice Smile

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