Urinary tract infections full of iron thieves

Research in the differences between E. Coli in the gut and in these UTIs help target treatment options.


Bacteria need iron, and as soon as they invade the human body, they are on the hunt for it. There is a limited supply of iron inside the human body where it is stored by the proteins tranferrin and ferritin.

Disease-causing bacteria have evolved by producing siderophores which are iron-chelating molecules. These molecules can bind to iron stored in ferritin and transferrin and "steal" it for the bacteria.

In this new study, the authors compared Escherichia coli taken from it's natural habitat in the gut and compared it to E. coli found in the urinary tracts of subjects suffering from urinary tract infections (UTIs). They found "epigenetic optimization" of the E. coli from the urinary tract:

Urinary tract infections (UTIs) are among the most common bacterial infections treated by physicians worldwide. Although symptoms of acute infection are often resolved with a course of antibiotics, the same bacterial strain often causes subsequent bouts of symptomatic infection. Escherichia coli are the most common bacteria causing UTI and the infecting strains are widely believed to originate from the gastrointestinal tract where multiple E. coli strains reside. Here, we use a novel mass spectrometric technique in a population of patients with recurrent UTI to identify how strains that cause UTI differ from other strains that were present in the gastrointestinal tract at the same time. We found that urinary E. coli strains preferentially expressed two small molecules called yersiniabactin and salmochelin. These molecules are called siderophores, meaning they are able to scavenge iron to support bacterial survival and growth. Synthesis and transport of these small molecules requires a coordinated network of proteins encoded by a collection of different genes. These findings suggest that new antibiotics directed against yersiniabactin or salmochelin-producing E. coli strains may be an improved, and more targeted, strategy to prevent recurrent UTIs.

Since some iron-transport systems also naturally transport antibiotics into the cell it is important to understand the molecular mechanism of iron transport here. Understanding these pathogenic bacteria may lead to new ways of either delivering or designing drugs which exploit this difference.

Many of us with Cushing's Syndrome/Disease (even if in remission) suffer from low ferritin. When we have an infection, due to our compromised immune system, we often have a difficult time recovering. When accounting for the iron-depleting nature of our infections, we are doubly plagued.

To read more:

• How some bacteria may steal iron from their human host
• Acquisition of siderophores in Gram-negative bacteria
• Pathogenic E. coli
  

Jeffrey P. Henderson, Jan R. Crowley, Jerome S. Pinkner, Jennifer N. Walker, Pablo Tsukayama, Walter E. Stamm, Thomas M. Hooton, Scott J. Hultgren (2009). Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia coli PLoS Pathogens, 5 (2) DOI: 10.1371/journal.ppat.1000305

Fiona Apple may just have it right....

He said 'It's all in your head' and I said 'So's everything' but he didn't get it --Fiona Apple in "Paperbag".

Pituitary tumors have a large spectrum pathology. These "little buggers" may cause large problems, also. Dr. Shereen Ezzat of the Toronto Cancer Institute has been studying pituitary tumors for several years, and presents the case for epigenetic disruption of gene expression which causes alterations of normal pituitary cells. Using the information he and others have gathered, he is hopeful treatments for these lesions/tumors can be developed. Since the morbidity/mortality of most with pituitary tumors is greatly increased, and the only long-term therapies so far are surgical or radioactive, improved treatment is anxiously sought by those of us with Cushing's or presently in remission.

According to Dr. Ezzat, pituitary tumors comprise 10% of the tumors surgically removed intercranially with increased morbidity due to invasion of surrounding structures. As a Cushie community, we know this only too well first-hand. All too often the only recourse for the hypercortisolemia due to ACTH producing tumor cells is a bilateral adrenalectomy. Radiation is often a secondary treatment to decrease tumor growth or Nelson's syndrome.

In another article, Dr. Ezzat says, "Some pituitary adenomas grow rapidly, producing symptoms of an intracranial mass, loss of normal anterior pituitary hormone production, and visual-field disturbances due to stretching of the overlying optic chiasm. They can invade downward into paranasal sinuses, laterally into the cavernous sinuses (thereby disrupting coordinated eye movement) and upwards into the brain. They can cause death by invasion of the brain."

But size does NOT always matter with these tumors. Dr. Ezzat also says "they can cause mood disorders, sexual dysfunction, infertility, obesity and disfigurement, hypertension, diabetes mellitus and accelerated heart disease. If untreated, hormone-excess syndromes can be lethal."

In the pre-print, recent article, Epigenetic Control in Pituitary Tumors , Dr. Ezzat discusses epigenetically-mediated gene dysregulation as a cause for the production of pituitary tumors. He explores the role of fibroblast growth factors and histone gene silencing and discusses the implications of the need to find the process or mechanism involved in order to develop new therapies.

Shereen Ezzat, M.D. (2008). Epigenetic Control in Pituitary Tumors Endocrinology Journal DOI: http://dx.doi.org/http://www.jstage.jst.go.jp/article/endocrj/advpub/0/0804240101/_pdf

This is not about obesity...

...again. In Obesity is a popular topic these days..... I mentioned "epigenetics". Epigenetics could promote obesity in next generation was released that same day by Baylor College of Medicine although I didn't see it 'til today. Fate? Coincidence? I have no clue, but here it is. And it's interesting.

"There is an obesity epidemic in the United States and it's increasingly recognized as a worldwide phenomenon," said Dr. Robert A. Waterland, assistant professor of pediatrics – nutrition at BCM and lead author of the study that appears in the International Journal of Obesity. "Why is everyone getting heavier and heavier? One hypothesis is that maternal obesity before and during pregnancy affects the establishment of body weight regulatory mechanisms in her baby. Maternal obesity could promote obesity in the next generation."

I do not think the explanation for obesity is a simple one anymore than I think chills are symptomatic of one illness. Nor should anyone.

Obesity is a popular topic these days.....

Is it a fad or is there really such an "epidemic" of obesity that it's become the topic of the year? I really can't answer that right now because I need to study it in more depth. I do know, however, that the mainstream media can grab onto a topic and worry it like a dog with a bone. Sometimes I just want to say "bury that dead horse already". Sometimes. A lot of the time.

But I'm not opposed to talking more about obesity as long as those talking about it are willing to help come up with viable, workable reasons with solutions and stay away from the attacks. I'm not persuaded the media sees the topic as anything other than another way to make money. It's a "hot" topic. That and gas prices.

Why not put both together in one topic? Oh wait, someone did that already: Increasing Gas Prices Could Be A Good Thing.

"According to a University of North Carolina study, the end result could be a 10 percent reduction in American obesity over the next seven years."

We could even combine it with politics! Wow...now that's a topic. No, I'm not talking about the very ill Ted Kennedy. Shame on you for thinking that!

Mr. Sali also announced a draft bill to "propose that the force of gravity, by the force of Congress, be reduced by 10%" to combat obesity. Mr. Sali said it was meant to parody a bill to raise the minimum wage, which he felt ran counter to the laws of economics.

Poor Australia....they are getting hit from all sides about it. Even their pets are obese. 33% of their cats and 41% of their dogs are overweight. (Who goes around and weighs all these animals?)

No, I don't take much of the media hype about anything seriously. I do take obesity seriously though. I've been fighting it for ages. Thus, this is a problem for me. I don't trust the hype, but I do observe the problem.

On the flip side, the BBC reports: Can genes explain rising obesity?

Contrary to conventional wisdom, the obesity epidemic is not restricted to people in Western countries who eat bad diets and are not very active.

In developing countries, it is estimated that over 115 million people suffer from obesity-related problems.

Experts believe that in many of these people these problems are not due to lifestyle but a condition called metabolic syndrome...There are many uncertainties about metabolic syndrome but one thing is certain - it cannot be explained entirely by genetics or lifestyle factors.

Betcha didn't read that one anywhere recently, did you? It's not newsworthy. A student newspaper caught wind of it, though. Yes, you can tell it's a student, but the sources are excellent. Well worth reading.

"This tells us that nutrition in utero is largely responsible for our epigenetic
programming and that under nutrition in one generation could explain the rise in
obesity, heart disease and diabetes in the next! It’s a far cry from the popular
cultural view that lifestyle changes are the be all and end all determinants of
good, or poor health - that everything boils down to personal decision
making..."

As with everything, take what you are reading with a grain of salt. I even challenge you make sure the statistics that are being quoted are real statistics. Anyone can make up numbers. And anyone can write anything on the internet. Including me.