It takes a nerd to get excited about bacterial biofilms!

[icnmgrjill]

Okay, I admit it! I'm a closet nerd. Always have been, always will be... it's a family genetics kind of thing when you have a brother whose a nuclear physicist and a sister who is an amazing wine chemist. So, I proudly announce that, yes, I am a nerd.... and it's "totally cool" some days... like today... to read something so exciting that you have to share it with others!!! So... put on your honorary nerd hat and read on.

When I was finishing up my degree in Pharmacology (don't ask me why I chose this major!), my senior Microbiology project on culturing antibiotic resistant infections. I gathered samples bathrooms, kitchens, floors, water fountains from my dorm at UCSB, the local hospital, various buildings around campus, cars, etc. Just small sterile swabs.. which we then used to innoculate an "agar" plate. An agar plate is commonly used in labs and, basically, it's like jello for bacteria. I wanted to see what bacteria, if any, would grow. Well, I found some whoppers. You know what they say.... hospitals may be where you go to get well, but there are some scary bacteria living on the floors, equipments, etc... and my project proved that yet again.

But, once I had a dozen or so agar plates growing large colonies of bacteria, we then put tiny disks of paper saturated with antibiotics on... to see if it would kill the bacteria... or if they would just keep right on growing. Amazingly, back in 1982, most of the bacteria we found was resistent to one or more antibiotics .. which means, of course, that they had mutated and learned how to defend themselves against the medication.

Who would have guessed that bacteria are smart... and can adapt and adjust to protect themselves... but as we all know.... many antibiotics are losing effectiveness due to overuse and the fact that bacteria have adapted to fight them.

In January this year, I read a study about college students in three or four northwestern states who all came down with bladder infections. What was interesting was that they all had exactly the SAME infection. Research later proved that it had come from contaminated meat that had been distributed to colleges in various states. In this case, the ranchers apparently overfed antiobiotics to the cattle until one nasty staphylococcus mutated and defeated it. This superbug then spread throughout the cattle herd... and, apparently, was viable even after slaughtering and cooking. Hmmm.. you ask... how could a bacteria do this??

Enter the biofilm. Imagine a supercolony of bacteria living behind a shield so strong that even sterilization by heat (autoclaving) can't kill it. Now imagine that that shield & colony can move at will ... that little colonies of bacteria can excrete a protective coating and then create a healthy little colony of buggers that can easily attach to themselves to animal tissue, human tissue, medical equipment, catheters and the like. Researchers have found that biofilms can actually move the length of a catheter... including directly into the human bladder. This could explain why so many people get bladder infections after catheterizations... and why my friend Jenny had many multiple resistent staph infections after undergoing peritoneal dialysis. Smart buggers they are.

Now, I can't tell you if the meat induced bladder infections were directly related to biofilms... but it's commonly accepted now that most bacteria live within some type of biofilm. How that translated into meat and human exposure may be very simple or very complex. Maybe the biofilm was just in the muscle... waiting for us to bite. Or maybe it came from contaminated equipment at the ranch or butcher. What it certainly shows that we should pay attention to any situation which can promote infections of all types.

If you're interested in the science and the current research on bacterial infections and biofilms (and want to hereby embrace your own nerd within), Medscape has just released a superb, comprehensive article, "Catheter Related Infections: It's All About the Biofilm" which is a must read for anyone struggling with UTI's or who is self catheterizing.

Read it at: http://www.medscape.com/viewarticle/508109

PS.... I want to start a Scott Hultgren fan club! If you don't know who he is... do a google search of his name!

[mom_in_ma]

Jill,
I'm a nerd too... I admit it. Thanks for sharing the interesting information.

That said, I just want to thank you for the work that you do here. This site helped me tremendously when I was first diagnosed and it helped me figure out the treatments that worked best for me. Thanks to you, I lead a normal life most of the time. I'm not sure I can ever fully express how greatful I am.

[Dixiefireball]

thanks Jill. Sounds like your talking about me with all these uti i get matter of fact i've got a IV in my arm now(comes out tomorrow) because I couldn't take nothing by mth to lick this infection. I'm going to go read the link you put up and book mark it. I do the at home treatments daily and get at least one real uti

[rhea]

Jill...so funny I too am a not so closeted nerd.The informtion is so interesting. I always wanted to work in research in bacteria and infectious disease (my brother is HIV + and I am unable to accept that we have no cure), either that or 17th century poetry (total geek) but baby ar 17 and 19-well too much school. Thanks for keeping us updated on so many different topics. Gonna go and check out Scott Hultgren, you haven't lead us wrong yet. Again, from all of us thanks for being a wonderful leader.

[Martha13]

Jill,

I don't think any urinary tract patient is a nerd to be interested in bacteria and biofilms. As you know some of us in Virginia (and now Canada) are doing research into a bacterial association with IC. You also know that many of us support the theory that the Gram positive species, Enterococcus, is associated with the symptoms of IC. Bacteria have always been suspected but many researchers have given up because they can't find any consistent species in IC patients - or even any type of bacteria at all.

On the contrary, using very sensitive culturing and testing techniques we can find all kinds of bacteria in patients and controls. The PCR, a molecular device, enables the researcher here, Dr. Helen Fillmore, to isolate Enterococcus by using selected primers (chemicals) specific to that species in a majority of IC-diagnosed patients. Others have published articles to the affect that they are unable to find signs of bacteria via PCR testing, but maybe they did not use primers that could recognize species present.

A doctor just told me he had a male patient diagnosed with IC but the local lab found "no growth". The doctor sent the specimen to United Medical Lab in McLean, VA requesting both routine and broth culturing. The report came back showing over 100,000 colonies of both E. coli and Enterococci. United is the only lab in the US (or world for that matter) doing broth cultures. We, patients, need to search and ask for better testing! The labs are not doing an adequate job for us and the medical profession is not demanding it.

A urologist at UCLA has written about a Rapid Pathogen Detection method to screen for urinary tract pathogens. http://cmise.org/images/citems/a_img_330_en_Seminar_Announcement_-_Liao.pdf The large laboratory testing corporations are not ever going to do broth culturing en masse. It is too time-consuming and labor intensive, but if there is molecular-based testing available hopefully they will get on the bandwagon.

There is a desperate need for this kind of testing! If any patients who read this live in the LA area it would be helpful to try to contact this MD to ask when it may become available in labs all over the US and abroad. Our preliminary research shows that with good testing much bacteria can be found. Asymptomatic women also have bacteria so there is something that causes some of us to be susceptible to infection. But bacteria are treatable, so it is good news if we prove this to be a cause. But first the medical and laboratory community needs to be screening chronic patients with better tests.

We will continue with our research. We are looking at whether the Enterococcus intracellularize, just as the E. coli have been found to form biofilms. Many IC-diagnosed patients who have been treated with the correct antibiotic have recovered completely, but it takes time to reach and eradicate these bugs.

We believe, just as with stomach ulcers, bacteria will one day be proven to be a culprit in IC!

Matha Foster

[Allibeth]

In my wildest dreams people at ICA, ICN, and UM become open-minded about infectious causes of IC, and we all band together to find a cure. It isn't just bacteria with biofilms or that become encapsulated or intracellularize thus resistant to abx (and nearly impossible to culture), but there is mycoplasma, mycobacteria, viruses, fungi, and goodness knows what is yet to be discovered that is difficult (or nearly impossible) to detect and treat, especially with mainstream culturing techniques and conservative antibiotic treatment (let us not forget -- since an earlier post mentioned HIV -- that HIV wrecked havoc for decades before discovery and then it took yet another few years to create a test for it). It took Dr. Marshall years and years to convince the medical industry that a bacterium causes ulcers, and it's only in the past 7 years that chlamydia in the blood vessels (which won't grow on your basic agar plate) was identified as a huge factor for developing heart disease. If urologists took care of people with scarred Fallopian tubes, we probably still wouldn't know about genital-chlamydia as urologists are so close-minded about finding infectious causes (in general) -- chlamydia won't grow on agar and they just wouldn't look farther. As my sister says, if it was middle-aged women in Lyme, CT that got aches and pains and ruptured knee caps from Lyme Disease the whole epidemic would have been attributed to some vague middle-aged female problem -- thankfully (well, not for the afflicted kids) enough children got Lyme that when their mothers demanded some attention they got it...and then the Lyme spirochete was discovered. There's so many examples of illness being improperly treated and then <bam> an infectious agent is discovered. If people want more info along these lines, please send me an email and I'll direct you to some sites that are on the cutting edge of infectious disease research.

[twiggy]

Oh dear, I must say that I am finding this rather depressing. Smart bacteria-- #$#$!!Having suffered more UTI's than I can count--and receiving a duel diagnosis of IC/prone to frequent UTI's for no logical reason--I am truly overwhelmed. I have long thought that my IC is some type of undetected bacteria since I NEVER, NEVER had any bladder problems prior to developing a seemingly unbreakable chain of UTI's. Now my bladder is a complete painful mess! For those of us now suffering from IC, it is frustrating to think how far we are from a cure. And to think how simple it would be if we could only detect the bacteria causing IC --if, indeed, it is from some undetected bacteria. I have done broth cultures, taken corresponding antibiotics, and still didn't get well. In addition, I was recently diagnosed from a culture with a type of bacteria that is often a result of surgical procedures. Now, get this. I HAVEN'T HAD ANY SURGICAL PROCEDURES FOR A YEAR SO HOW COME THIS BACTERIA SUDDENLY APPEARED IN MY BLADDER? Hmmmmm... keep up the excellent work, Jill. I find being a nerd particularly problematic when it comes to dealing with physicians as most seem to think the general population is stupid. Then, add being a woman to the nerd factor and you get to go through life as a very frustrated person!

[Martha13]

Twiggy,

Sometimes even broth cultures cannot indentify all the urogenital bacteria present. Dr. Attila Toth, GYN, who practices in NYC is very good at culturing in his own lab. He has a very aggressive antibiotic treatment for those who do not respond to oral antibiotics. Several IC patients are now seeing him. His specialty is infertility which he thinks is due to undetected bacteria. Allison at allison212@hotmail.com is an RN and has seen him. Feel free to email her with any questions about his treatment. There are many species present in the female (and male) urogenital system and Allison has started a GU infection Yahoo group to discuss this.

Martha

[purpleviolet]

Hi all you experts,

I'm really flaring now, just before a long vacation drive! Boo! Had a culture a while ago of s.veridans 50,000 which uro said was above the normal amount, but since I was away never got to take any antibiotics, but that flare subsided by itself. Now I wonder if this flare is related to that bacteria coming back again? Any experts know what this bug is? How does all this finding of weird bacteria jive with the latest research that showed no dna of bacteria or viruses in IC bladders? Seems like the research is going in 2 different directions.

[icnmgrjill]

Alibeth,

We're certainly not closed minded about the role of bacteria for some IC patients but I'm very clear in saying that it is not the cause of all IC... because many patients have very specific onsets unrelated to bacteria... such as the man who fell off his roof and developed IC that night at Stanford Univ., or the woman who developed IC after having a very rough labor which tore her muscles or the many many people who seem to develop IC after what they self admit is an addiction to coffees and sodas. Or, in my case, what began as a chemical burn due to chlorine exposure. Also, we have a strong genetic component to IC that is also unrelated to bacteria.

Could bacteria be a contributing factor for some IC patients? Sure, I've always said that. But, I do not believe that it is a contributing factor for ALL IC patients. As a subset of IC, I think it's one of the smaller contributing factors. I think that muscle injury is a much stronger contributing factor over all... after spending ALOT OF TIME interviewing many of the best IC and bacteria researchers.

As to collaboration?? I've tried on many occasions. They simply aren't interested. I doubt they ever will.

I did, however, ask two leading advocates on the web (you know them) for the bacterial theory to write a story for our newsletter just in the past two weeks. They both said "no" for lack of data supporting their theory. So... what I can say. I tried.

Jill

[Martha13]

Jill,

As one of the ardent supporters of the theory of a strong bacterial connection I am replying to your most recent post. I am sponsoring research to the tune of over $100,000 of my own money to investigate this connection. The lead researcher, a molecular neurobiologist who uses the PCR in brain tumor research, is donating her time. We now have a microbiologist from Canada whose expertise is in E. coli and biofilms. But research takes time and since we are working on a shoestring we do not have our study results completed and ready to publish, although at this point they are promising. When the final results are in it will be appropriate to write a summary for your newsletter prepared by the researcher.

It is difficult to get grant money from the NIH/NIDDK and our first proposal was turned down with constructive comments. (At the time of submission we did not have a microbiologist on our team). But we are the "new kid on the block". Much of the money goes to the "known" researchers and we all know who they are. The Fishbein and ICA money also goes to these people. So far after millions of dollars and years of research they have not found a cause nor a really good treatment. We know that the study done by the U of MD in 2000 using antibiotics was not a good study. In the first place they were unable to find any bacteria in the 25 IC patients they used. But they treated these patients with 5 different antibiotics for 3 weeks each, in a scattershot approach. In the end 48% improved which they did not think was a big enough difference compared the placebo group. Those of us who have used antibiotic treatment know that 3 weeks on the RIGHT antibiotic is not long enough, and it has to be the antibiotic that is appropriate for the PATHOGEN isolated. And those of us who have succeeded on antibiotics have always had a pathogen or would not be put on antibiotics. Dr. Fugazzotto could find a species in almost 100% of the patients he tested, the one lab now doing broth cultures can also find several species of bacteria, and the PCR can find Enterococcus which is the only species we have designed it to look for at this point. Others have used the PCR but have used a general primer (chemical) while our researcher said you must use primers specific for the pathogens you are looking for. As I wrote you there is now a molecular Rapid Pathogen Detection test being developed at UCLA and that will be the wave of the future. The current agar plate test is not adequate and no big lab corporations are going to do broth cultures which are time-consuming and labor intensive - not profitable for them. Many of us have had "no growth" reports from the commercial labs when the broth culture shows plenty of bacteria - it just takes the right medium and allowing a longer time to grow them.

Why did 48% of the patients in that study improve? Would they have improved more if a species of bacteria had been found and treated with the right antibiotic? That would have been a legitimate test of antibiotic treatment. We are finding that it takes 6 months to a year on the right antibiotic for full resolution of the symptoms. But many have had the symptoms for years and so symptoms do not resolve overnight anda the bladder wall needs time to heal. We also know that many asymptomatic persons can have the same bacteria without symptoms but this is true in other infectious diseases - it is believed 30% of the population has H. pylori in their stomach but only about 20% develops an uler and no one knows why.

As to your examples of those you know of who have had the onset after a significant event or trauma to the bladder, I have no doubt this is true. As B J Czarapata said in an interview with you she believes this in an "opportunistic" infection. Somethings weaken the bladder's defenses and the bacteria already present invades. We also know that E.coli, at least, forms biofilms and hides from defenses. Other species may do that also and we are looking at that. We know it is not "just the presence of bacteria". Many things could contribute: the change in hormonal levels, the use of birth controls methods which changes the flora of the vagina where bacteria migrate first and where resevoirs of bacteria can build up, the immune system dysfunction, etc. Much more research needs to be done but the researchers and MDs have been conditioned by training and past research to believe that "IC is not bacterial". I could point to another study just published in the Journal of Urology that was flawed. They only tested for E. coli in bladder biopsies and since they did not find any they drew the conclusion that " there is not an infective eitiology for IC". What about all of the other pathogens such as Enterococcus, Staphylococcus, Klebsiella, Pseudomonas that can find their way into the bladder? These were not tested for and ruled out.

As to the examples you gave of those whose IC started with a specific event - males have these same events in their lives and yet IC is predominantly a female problem. We know due to anatomy it is much easier for bacteria to enter the bladder which is why females are the primary sufferers of UTIs. Females suffer much more trauma to the urogenital tract and hormones are critical to health in that area and much more subject to change.

I really believe when some of the more sophisticated uro testing comes online more pathogens will be identified. There is no question they are there and it is time for the agar plate (used as the gold standard for 50 years because it is cheap) to be replaced. We hope our research will hasten the powers-that-be to see the need for better culturing, especially for chronically symptomatic women. Perhaps if the pathogens were found quickly the treatment time would be shortened, too.

The first challenge is to improve culturing and once that is more universal research will begin to look more seriously at bacteria, which is what was originally sought as a cause. Now that we have molecular methods to look for it there is hope for the first time since Dr. Fugazzotto began to find it in his lab. He still deserves much credit for opening up so many of us to the possibility of a cure!

Martha Foster

[Allibeth]

Hi Jill,
You mention muscle injury. I'm assuming that you're referring to serum markers of muscle injury/inflammation being increased in some people with IC. Infection can cause an elevation -- either directly or indirectly. For instance, take heart disease. Chlamydia of the heart vessels leads to cardiac muscle injury and (and subsequent elevations in CPK and its cardiac subset CPK-MB). Heart disease -- like IC -- has many factors. Certain people may have a genetic predisposition to heart disease, but unless there's a trigger -- be it infection or smoking, etc -- they might never develop the disease. Indeed, people with a predisposition to heart disease that have been on antibiotics that respond to chlamydia are less likely to suffer a heart attack.

It's important to keep in mind that infection can cause inflammation and muscle injury. Infection can cause scar tissue and ulcers. When infected tissue is stretched it can cause bleeding. I wouldn't be surprised if it was discovered that Hunner's ulcers and glomerulations -- at least in some cases -- are caused by infection, and that people with these symptoms were genetically susceptible.

You referred to me in your post about publishing in your newsletter. You offered to possibly let me publish something in your newsletter, and I said I couldn't now as I have some projects going on that have a higher priority than writing in your newsletter, but maybe in the future. It has nothing to do with the dearth of research already done re: infectious disease as you claim -- in fact, I fully acknowledge the lack of research, and this is what causes me to want to get the word out through articles and letters to NIH/politicians and also media with high circulation. So, believe it or not, I didn't jump at your offer like "omigod, Jill will let me publish something in her newsletter! Yippee! If only I had more research backing me up, but alas I don't so I must be lying and therefore refuse her offer." Your inference of this is appalling. Of course we need more infectious disease research! No one is denying this! (And by the way, no one I know has said that ALL cases of IC are related to infection, and that this is the only factor.) Perhaps, since ICN makes money by selling products, your organization could contribute money? There's a medical college accepting contributions for researching infectious agents in people with IC -- I'll forward the info to anyone that's interested.

[icnmgrjill]

Allibeth,

The most precious and meaningful gift that I CAN give to anyone is to give them the chance to share their thoughts in an article on our website. If someone says no, for any reason, I can't change that. I've made the offer and it stands.

And I wasn't referring to your refusal... but to two others... so please don't take make it personal. It wasn't... nor isn't.

Jill

[tigger_gal]

Allibeth,
Why would you say... "omigod, Jill will let me publish something in her newsletter! Yippee! It was an offer that she has offered to many. You make Jill sound like a some type of person that looks down on you and us.. I am going out on a limb here... But I am Speaking for EVERYONE on these boards. Jill is the nicest, reasonable, kind hearted, caring, loving, and understanding lady I have ever had the pleasure of speaking to. She offered you an opportunity, and you chose to pass it up at this time.. It is not Jills fault.
ok then you go on to say.... If only I had more research backing me up, but alas I don't so I must be lying and therefore refuse her offer." Your inference of this is appalling What on earth is getting inferred here? You have spoke your peace on the boards, and you have an offer standing to post in the news letter as a theory, to me it seems your offended by the fact you can't prove anything. No one has ever stated that you were lying, I am sorry you feel that way.
ok next thing implied Perhaps, since ICN makes money by selling products, your organization could contribute money? There's a medical college accepting contributions for researching infectious agents in people with IC -- I'll forward the info to anyone that's interested. How do you know what the ICN does with their money.. I know personally that hundreds of dollars went out at Christmas to help our children.. I know a $1,000.00 went out to help the Katrina Victims. I know that these boards and Jill provide for us are not free like the Yahoo boards. No one has the right to tell Jill how to spend her money, no more then anyone has the right to tell us how to spend ours.. How much do you donate to research? I don't donate any, I have a hard enough time donating to my bills, and groceries each month.
Jill did not have to create these boards for all of us to come to daily, weekly, monthly, what ever the case may be... However, she did, and she still pays to keep them up and running. So if Jill never donated a dime to research because she sinks all her money into keeping these boards and chat rooms open that fine by me.. WHY??? because she is actually donating in her own way.. Jill is donating her time, her life and alot of money into these boards so WE as icers have a place to come and talk...

Thanks Jill for all your hard work, and, effort fo having the strength and courage to run these boards..

Brat

(From Jill - Thanks Brat! Actually, a lot of people donate hundreds of hours to keep this site going too.. and they also deserve recognition. It's along way from being just my boards now!)

[dancemomof2]

Well said Cindy, not much more I could add that would be polite.