Biofilms & Chronic Bacterial Infections

[Harrison]

Last year, I met a smart medical professional. She's a woman who knows a great deal about the role of pathogens in causing chronic inflammatory diseases, particularly “newer” types of bacteria that are called “mycoplasma” AKA cell-wall deficient bacteria.

She was kind enough to send me an article on biofilms, which are "colonies" of bacteria -- all of which can lead to big problems for patients with medical devices. Here’s an excerpt from her email to me. Please carefully read the long article herein:
_______________________________________

Subject: Biofilms & Chronic Bacterial Infections

The more I think about it, I'll bet that biofilms are the main culprit in infections which involved steel pins and plates and such. It has occurred to me that this explains my (now deceased) mother's long (Th1-like) illness following a bad injury from a car accident that required a surgical steel pin in her hip. I don't know why it took me so long to figure this out, but after seeing this article, it finally dawned on me that this explains her 3.5 decades of chronic health problems

It also makes me realize that biofilms are probably where you need to be focusing your time and energies in relation to spine patients.

http://www.jci.org/cgi/content/full/112/10/1466

I stumbled on this because I've been researching "antibiotic resistance" in chronic prostatitis for a friend. One thing led to another until I eventually decided to follow some of the biofilm leads. Somehow or other, I stumbled upon this article in the process. I hope you find it interesting and helpful.

ML
_______________________________________


Case in point: I now know for a fact that at least one patient with serious, severe post-op pain had a spinal device removed; and it was sent to the pathology lab for analysis. And it did test positive for bacterial infection (high enough titer to be unequivocal, I assume). So, for those people that have relentless, debilitating pain, give this article some serious thought.

For other patients that have other complications that are unusual, perhaps the cause may not be “biofilms” per se, but still involves similar pathogens – on a systemic level.

I also understand we can’t be microbiologists here, sleuthing our way to a diagnosis. But I also know that many patients are not getting answers. Case in point: the person that has had a long list of unusual myalgias, neuropathies (and more) was told his blood results are “normal” and “fine.” But visual microscopy revealed a totally different story! Recall my October 27th post.

This community would benefit greatly by getting help from a small team of pathologists and dedicated diagnosticians. We’ve barely scratched the surface (no pun intended) on this troubling issue…

[kanutta]

This is interesting, and useful to have in mind.

But what have struck me recently, after reading different articles, is that there are so many structures in the spine that can not be removed surgically, that can be the source of pain after fusion or ADR.
The PLL, the vertebral body, the meningues_ especially the dura and the arachoidea, the facets, the uncovertebral joints ...I'm sure there are more too.

There is so much focus on the disc and the nerveroots, and in some extent the facet joints...but there are many more structures that can be pain generators too...no?

More funds for research are needed, but as spinal disease is not lethal, there is little research going on compared to cancer and heart research.
But spinal disease costs the society more than cancer and heart added.

Strange...

[Harrison]

More funds for research are needed, but as spinal disease is not lethal, there is little research going on compared to cancer and heart research.
But spinal disease costs the society more than cancer and heart added.

Strange...

Well said...I could not have said it better. That's one of the main reasons why the Arthroplasty Patient Foundation is a new non-profit. To me, it is quite sad that very little financial and human capital (that is helping us now in 2007) is committed to a problem that contributes to the #1 reason for lost work time!

We, and our spines, are much more than a "modular" system of components. The organization will address a much more sophisticated approach that addresses (the many possible) root causes of this terrible disease...or diseases.

Lest we forget, patients have died on the table during spinal procedures (the number is very small, but if you are the "1 out of whatever number," does it matter?). Some of you may recall those terms & conditions you acknowledged in the consent form?

We'll talk about consent forms, living wills in the coming weeks. It's interesting this issue has not come up before -- at least explicitly.

[Linda]

This hit me really hard today as I was at the doctor. I guess because spine disease isn't "generally" life threatening it isn't deemed worth enough for research funds. Maybe this group needs to somehow raise awareness for research for spine disease. I wouldn't even begin to know how to do that but I would sure be willing to help if anybody has any ideas???
Linda

[cervie queen]

Life threatening? Not significantly, unless you consider the number of spinal patients who have considered suicide because of their inability to function or amount of pain or both.

[Harrison]

But what have struck me recently, after reading different articles, is that there are so many structures in the spine that can not be removed surgically, that can be the source of pain after fusion or ADR. The PLL, the vertebral body, the meninges, especially the dura and the arachoidea, the facets, the uncovertebral joints ...I'm sure there are more too.

Kanutta, I meant to single out this thought some time ago, as I thought it was particularly well said. If in fact the etiology of spine disease is multifactorial, and may involve more structures than the disc, should we always expect stellar results from ANY spine surgery?!

Perhaps spine patients with disease limited solely to spinal discs are the "lucky" ones. In the meantime, the new foundation will work to develop programs for FAR better diagnostics for ALL spine patients. There is so much more diagnostic capability that is needed!

[Terry]

Is that you Richard with the road bicycle? You ought to travel to Norther Michigan and I'll hop on my Colnago C-40 to train you on some hills. Nice project and I hope you have a Merry Christmas.

Terry Newton

[Slackwater]

Originally posted by Harrison:
Last year, I met a smart medical professional. She's a woman who knows a great deal about the role of pathogens in causing chronic inflammatory diseases, particularly “newer” types of bacteria that are called “mycoplasma” AKA cell-wall deficient bacteria.

She was kind enough to send me an article on biofilms, which are "colonies" of bacteria -- all of which can lead to big problems for patients with medical devices. Here’s an excerpt from her email to me. Please carefully read the long article herein:
_______________________________________

Subject: Biofilms & Chronic Bacterial Infections

http://www.jci.org/cgi/content/full/112/10/1466

BioFilms,

Orthopaedic Research Society,
Volume 25, Issue 7 , Pages 858 - 866
Published Online: 5 Apr 2007
Copyright © 2007 Orthopaedic Research Society

"Vancomycin covalently bonded to titanium alloy prevents bacterial colonization

Abstract
Periprosthetic infection is a devastating consequence of implant insertion and can arise from hematogenous sources or surgical contamination. Microbes can preferentially colonize the implant surface and, by forming a biofilm, escape immune surveillance. ..."


Volume 25, Issue 1 , Pages 2 - 10
Published Online: 25 Sep 2006
Copyright © 2006 Orthopaedic Research Society.

Biofilm formation by bacteria isolated from retrieved failed prosthetic hip implants in an in vitro model of hip arthroplasty antibiotic prophylaxis"

[Harrison]

June 12, 2008
Researchers identify biofilms that cause infection

COLLEGE STATION, Texas — Understanding the way bacterial cells "talk" to each other could lead to more effective methods for fighting the often persistent and serious infections caused by the biofilms they form, says a Texas A&M University professor of chemical engineering who not only has deciphered their language but also discovered how to quell their conversation.

Examining Escherichia coli bacteria — widely considered a model organism for microbiology studies — Professor Thomas K. Wood of the Artie McFerrin Department of Chemical Engineering at Texas A&M has succeeded in identifying, decoding and even modifying cell-to-cell signals so that biofilm formation is inhibited.

His findings are covered in a series of five published articles, two of which appear in "The International Society for Microbial Ecology Journal" — a member of Nature Publishing Group's stable of scientific publications. In addition, his progress is detailed in "The Public Library of Science ONE," "Applied and Environmental Engineering" and in "BMC Microbiology."

Wood's work is important in addressing the widespread health issues resulting from bacteria in its biofilm form. Put simply, biofilm is a protective and adhesive slime excreted by bacteria that have joined together to form a community. The substance can grow on a variety of living and nonliving surfaces, including submerged rocks, food, teeth (as plaque) and biomedical implants such as knee and hip replacements.

And where there's an infection, there is usually biofilm.

The National Institutes of Health, Wood noted, estimate that about 90 percent of infections in humans are caused by biofilm. The Centers for Disease Control estimate biofilm to be present in 65 percent of hospital-acquired (nosocomial) infections. Biofilms have been linked to everything from gum diseases to cystic fibrosis. They typically are the cause for the fatal infections that develop post surgery. More commonly, biofilm is the chief culprit behind the nagging ear infections so common among children.

"It's been only in the last few years that pediatricians have realized that children are crying day in and day out from ear infections because it's a bacterial biofilm on their eardrums," Wood said. "Prior to that, the approach was to treat the infections with drugs that got rid of bacteria but not bacteria in a biofilm, and it was completely ineffective.

"When bacteria are growing within a biofilm, that growth takes place in a different way than when bacteria are swimming freely in suspension. Pharmaceutical firms make antibiotics to kill bacteria in suspension. Those are 1,000 times less effective on a biofilm. It's only in the last 10 years that we've realized people have died not because of free-floating bacteria but because of bacteria in a biofilm."

Wood's efforts to mitigate biofilm formation began with the recognition that construction of this substance was anything but random. To the contrary, biofilm formation is an extremely ordered process — a fact affirmed by examining biofilm structure on a microscopic level.

Though it appears as slime to the naked eye, biofilm is actually composed of several hills and valleys of varying heights and depths. These structural differences allow for nutrients to make their way to all bacteria within the biofilm community, Wood said. Despite the numerous formations present, these pillars and plateaus seldom collide with each other. The reason for that, Wood said, is that each bacterial cell is able to "talk" to one another and signal its location so that neighboring cells do not begin construction in an occupied space. If that happened, the bottom layers of the community could be sealed off from the nutrients on which they depend, Wood explained.

In-depth examination of those critical signals by Wood and his team of researchers found that E. coli relies on a compound known as autoinducer-2 (AI-2) for biofilm formation. Each E. coli bacterium produces this compound and then releases it in the cell¿s external environment. Eventually a large amount of AI-2 becomes present outside of the cells, and through a process called quorum sensing each bacterium re-absorbs the AI-2 when a specific concentration has been achieved, Wood explained. When the AI-2 re-enters the cells it activates an entirely new set of behaviors for the bacterium - in this case, signaling when and how to begin building a biofilm.

"What we're doing is examining how AI-2 is prompting the cell to make more biofilm," Wood said. "Sugars are the mortar. We identified the specific type of mortar — the sugar known as colonic acid. We found that AI-2 helps E. coli produce more biofilm by making colonic acid, which is a kind of sugar. If you can understand how a biofilm is formed, then you can start to attack it at different stages."

And that's exactly what Wood has done.

Further research by Wood revealed that E. coli uses two different signals to control biofilm formation. Which signal is utilized depends on the temperature of the external environment, Wood said. In other words, these bacteria change their "language" if they are inside the body versus outside the body. Whereas AI-2 is the signal utilized by E. coli inside the body, Wood discovered that a compound known as indole is used for biofilm growth outside of the body — for instance on surgical replacement parts yet to be implanted.

"The second signal that we unraveled is indole — a derivative of amino acids," Wood said. "Amino acids are what proteins are made out of. All living things need to make amino acids. All living things make this specific amino acid called tryptophan. It turns outs E. coli converts tryptophan into indole."

Armed with that knowledge, Wood discovered a method for inhibiting biofilm formation by modifying the indole signal in a way that would confuse the bacteria. In lay terms, think of Wood's achievement as adding a few extra letters to a spoken word. The resulting gibberish is not understood by other bacterial cells in the community, and the massive construction project never gets off the ground.

"Once we realized that indole was the signal, then we could slightly modify indole by putting an OH [hydroxide] molecule on it." Wood said. "The new compound is called 7-hydroxyindole. We also found that a different type of modification would not be successful. We learned that you can trick bacteria, but you have to do it well, and another modification does not have any effect on stopping biofilm formation.

"By adding that hydroxyl group and making the 7-hydroxyindole, we turn off the bacterium's ability to talk. We short-circuit the bacterium, and it becomes less of a bad actor."

For more information, contact
Source: Thomas K. Wood
(979) 862-1588
thomas.wood(at)che.tamu.edu

Written by: Ryan A. Garcia
(979) 845-9237
ryan.garcia99(at)tamu.edu

News Story 1892, June 12, 2008

Direct page link:
http://engineeringnews.tamu.edu/news/1892

[Twiz77]

Wow. Thanks for that information. Not only am I going to follow up on my MRI results (which I get tomorrow) and meet with NS and orthoped - BUT - going get those blood tests run for all sorts of pathogens and other items that may be taking safe harbor in my body before undertaking any type of procedure is done for this spine. I have several friends with immunity issues/disorders and have been perplexed that none of my drs thought to run blood tests. I said no - why would they since we were focused on the MRIs, CTS and Xrays. But - as I have been learning - the human body is an amazing thing....