This week I'll be blogging at Scienceblogs.com, specifically on the pages of its new book club. So please join us in a discussion about the intriguing and controversial issues brought up in Carl Zimmer's new book, Microcosm: E. coli and the new science of life.
I've had the pleasure of watching Carl's writing career evolve over the last 18 years, since the day he climbed on board the Science Digest/Discover magazine train in 1990. 
Polyphenols, a class of phytochemicals abundant in red wine grapes, appear to reduce the ability of bacteria to cause cavities, according to a Rochester University Medical Center study published in the Journal of Agricultural and Food Chemistry.
The findings suggest that specific polyphenols, present in large amounts in fermented seeds and grape skins, interfere with the ability of bacteria to form the sticky biofilms that contribute to tooth decay. Beyond cavities, the compounds' action suggests a new way to block the kind of bacterial biofilms that cause life-threatening, internal infections.
Such an approach embodies the emerging recognition that anti-bacterial drug design needs to move beyond bacteria-killing antibiotics toward drugs that don't, by their nature, favor the success of resistant strains. By taking away a microbe's ability to cause disease but leaving it in place, the grape compounds may do just that.
"The message is not 'drink more wine to fight bacteria,'" says (spoilsport) Rochester researcher Hyun Koo, DDS, Ph.D., of the medical center's Center for Oral Biology. "We hope to isolate the key compounds within the winemaking waste that render bad bacteria harmless, perhaps in the mouth with a new kind of rinse."
The research team cultured oral bacteria on fake tooth enamel (photo) to test their grape compounds' biofilm blocking activity.
Good news for the fight against drug resistance came with two, short items in the business sections of last week's newspapers. Back-to-back FDA approvals gave U.S. doctors rapid tests for both MRSA (methicillin resistant staph aureus) and a panel of a dozen common respiratory viruses.
Both diagnostic tests use gene amplification, or polymerase chain reaction (PCR), to identify their targets. Most importantly they do so fast --- in a matter of hours rather than days, the latter being the standard with traditional laboratory cultures.
| Staph. aureus, photo credit unknown
This is such great news because without such rapid diagnostics, doctors routinely resort to powerful antibiotics when treating infections--as a hedge against the worst possible culprits. This is a particular Catch 22 in hospitals: Withhold the antibiotic and you risk losing a patient to a multidrug-resistant superbug such as MRSA. Routinely put patients on heavy-duty antibiotics and you're sure to breed bacteria that can shrug off still more antibiotics.
In addition, wiping out a patient's "good," or protective, bacteria with antibiotics leaves the body vulnerable to invasion by dangerous bacteria in their environment --- hospitals being the most dangerous places in this regard.
The first of the new rapid tests is BD Diagnostics' GenOhm StaphSR Assay for detecting MRSA. The assay makes clever use of a pair of linked gene-probes. One end lights up when it finds a gene unique to Staphylococcus aureus. The other does so when it finds the cassette of genes for methicillin resistance. Earlier versions of the test produced false positives when patients harbored both drug-susceptible Staph. aureus and one or more harmless bugs that happened to carry the methicillin-resistance cassette. By linking the two probes, the newly approved test lights up only when it finds both genes in the same bacterium.
Luminex's xTag Respiratory Viral Panel simultaneously probes for the 12 viruses responsible for 85 percent of respiratory infections, including common colds and flu. This can help physicians identify the majority of respiratory infections that DON'T call for antibiotics (which target bacteria, not viruses). Unfortunately, the panel does not rule out the possibility that a patient with a viral infection is simultaneously infected with a disease-causing bacterium.
The Food and Drug Administration (FDA) just gave its go-ahead for a clinical safety trial using a genetically engineered tooth bug to prevent cavities.
As described in Good Germs, Bad Germs, oral microbiologist Jeff Hillman has spent nearly a decade trying to bring his cavity-fighting Streptococcus mutans to human trials. Ordinary Strep. mutans is the culprit behind tooth decay. It does its damage by excreting enamel-eroding acids.
Hillman needed three steps to create his "probiotic" replacement strain in the mid-1990s. First, he found a naturally occurring strain of Strep. mutans that could elbow out anyone's pre-existing version. One kind of Strep. mutans or another colonizes virtually all of us around the time we sprout our first baby teeth. And once in place, our native tooth bacteria tend to stick around for life.
Scores of researchers have spent decades trying to rid the mouth of its entrenched tooth bugs, with no success. Once Hillman found a natural Strep. mutans that could do the replacement job, he knocked out its gene for acid production. Unfortunately, that pretty much killed it. The bug needed to excrete acid to dispose of its waste.
So Hillman knocked in a gene for an alternate route of waste disposal--alcohol production. Hillman lifted this gene from Zymomonas mobilis, the bacterium used to make "pulque," or Mexican beer. No, the resulting creation didn't make enough alcohol to make anyone remotely tipsy. However, it crossed the line from natural probiotic to "transgenic organism." After years of successful tests in animals, in 1998, Hillman became the first to approach the FDA requesting permission to use such a live transgenic in people.
FDA reviewers required him to install a failsafe-a way to get rid of the bacterium should it ever, for unknown reasons, cause trouble. He knocked out more genes-rendering the microbe unable to survive without a twice-daily supplement of an amino acid. To keep the bacteria alive, volunteers would need to swish daily with a mouthwash containing this nutrient.
Still, the approval dragged on, with Hillman learning that the FDA had lumped his tooth bug in the same category as potential bioweapons. Finally, in 2006, Hillman's company-Oragenics-was allowed to proceed with a mini safety trial-two people with full dentures that they could plunk into bleach at the end of a week.
This week Hillman got word that the FDA has approved a real safety trial. "Actual humans with real teeth!!!" he exults. "Young, healthy males." The volunteers will be isolated in a biohazard ward for the study's one-week duration.
For all the Frankenbug implications around transgenic organisms, I'm excited to see this research move forward. Tooth decay is no mere nuisance for the hundreds of millions of children and adults without access to dental care. Even here in the affluent US, untreated cavities are again on the rise, most likely due to the rising costs of dental care and dental insurance.
Okay, this post is going on too long. For a more disturbing alternative to fighting tooth decay, here's a track back to a post on Antibiotic Gum. For Oragenic's somewhat slick description of Hillman's tooth transgenic--the company calls it SMaRT, for Strep. mutans Replacement Therapy-- go here. And for Hillman's scientific description of the bug's creation, go here.
Scary superbugs continue to dominate this week's news with a major article in The Wall Street Journal. But buried in the horrific rundown on community MRSA and deadly hospital pathogens is the best news I've seen in a long time.
Near the end of Theo Francis's "Putting Superbugs on the Defensive," he reports: "[The University of Pittsburgh Medical Center] requires physicians to get approval from an antibiotic-management team when using certain high-powered antimicrobials that could affect the body's natural defenses against the bacteria."
The bacteria that Francis references is a an extremely toxic, hospital-bred strain of Clostridium difficile, which moves in when antibiotics raze the intestinal tract's normally tight knit community of native bacteria. Ordinary strains of C. difficile are ubiquitous in our environment and have long been the primary cause of so-called antibiotic-associated diarrhea, which runs the gamut from annoying to life-threatening. As regular readers of this blog know, US hospitals bred a highly deadly strain of C. difficile sometime in the late 1980s. Since then it has killed thousands of hospital patients, many of them having checked in for routine procedures that involved a course of antibiotics.
Some infection control specialists dared to hope that toxic C. difficile would be the jolt that would wake physicians to the dangers associated with razing their patients’ “good” bacteria. C. difficile isn’t the only superbug that moves in when antibiotics open up the parking places in the intestinal tract. Case Western’s Curtis Donskey, for example, has shown that the longer hospital patients remain on antibiotics, especially powerful gut-razing antibiotics, the more likely they are to pick up and spread vancomycin-resistant enterococcus (VRE), one of the most drug resistant and dangerous of hospital superbugs.
Powerful antibiotics are life-saving drugs, to be sure. But like most forms of chemotherapy, they have potentially dangerous consequences. It’s heartening to see hospitals using them more wisely. The reward: Francis reports that the Pittsburgh Medical Center has slashed its C. difficile infection rates by two-thirds from an all-time high in 2000.
My bad: I should have posted this days ago. Please join me for a live Internet discussion, "Can Germs Keep Us Healthy?," today at noon Eastern Time on Newsweek.com. Either link will take you there. You can submit questions beforehand as well as during the discussion. Thanks!
Vaccine dangers are back in the news, but The New Scientist points out that "a question mark hangs over the credentials of experts advising parents in the latest autism court case."
These expert witnesses include doctors promoting their use of chelation therapy for treating autism, this based on their claim that the disease is caused by mercury toxicity. Specifically they implicate the form of the metal contained in the vaccine preservative thimerosal.
Chelation therapy, as yet unproven for treating autism, comes with its own risks--including known side effects of liver toxicity and bone-marrow damage.
Of note, the form of mercury used in vaccines--ethyl mercury--does not accumulate in the body as does methyl mercury, the type associated with neurotoxicity (nerve and brain damage).
Headlines about the high-profile lawsuit are sure to sustain the enduring public fears around childhood vaccines. Over the last decade, the Insititutes of Medicine has pursued extensive research aimed at ferreting out any increased health risks associated with the mercury-based preservative thimerosal. Meta analysis of dozens of scientific studies found none. Nonetheless, US vaccine makers have removed thimerosal from all "baby shots" and now offer mercury-free formulations of most adult vaccines.
Tellingly, rates of autism have not dropped in the 8 years since manufacturers began phasing thimerosal out of US vaccines--as would be expected if this mercury-based preservative was to blame.
The New Scientist notes the similarity to the recent UK court cases and scares that led to a precipitous drop in childhood immunizations against measles, mumps, and rubella (MMR) in that country. The resulting mumps resurgence recently spilled over to North America, in the form of several mumps outbreaks thought to have been sparked by British visitors.
The bound page proofs are now out, and Good Germs, Bad Germs has its first review--from Publishers Weekly. Here it is ...
Good Germs, Bad Germs: Health and Survival in a Bacterial World
Jessica Snyder Sachs. Hill & Wang, $25 (336p) ISBN 978-0-8090-5063-5
Science writer Sachs (Corpse) makes a strong case for a new paradigm for dealing with the microbial life that teems around and within us. Taking both evolutionary and ecological approaches, she explains why antibiotics work so well but are now losing their effectiveness. She notes that between agricultural antibiotic usage and needless prescriptions written for human use, antibiotic resistance has reached terrifying levels. A decade ago, resistant infections acquired in hospitals "were killing an estimated eighty-eight thousand Americans each year... more than car accidents and homicides combined." Our attempts to destroy microorganisms regularly upset useful microbial communities, often leading to serious medical consequences. Sachs also presents evidence suggesting that an epidemiclike rise in autoimmune diseases and allergies may be attributable to our misguided frontal assault on the bacterial world. The solution proposed is to encourage the growth of healthy, displacement-resistant microbial ecological communities and promote research that disrupts microbial processes rather than simply attempting to kill the germs themselves. Despite the frightening death toll, Sachs's summary of promising new avenues of research offers hope. (Oct. 16)
The teeming bacterial kingdom in our digest tract is certainly getting its “15 minutes of fame” thanks to the research of gastroenterologist-turned-microbiologist Jeffrey Gordon and his team of young post-docs at Washington University, in St. Louis.
In December, Gordon’s crew extended their string of high-profile papers with two Nature reports. One describes how weight loss produces a profound change in what lives in our guts.
The other documents how the Wash U researchers found they could send germ-free mice down the road to either leanness or obesity by inoculating the animals’ intestinal tracts with either a “lean microbiota” or an obesity-related one (either the Bacteroides thetaiotaomicron or Eubacterium rectale, respectively).The reports generated scads of press on “microbesity” and “fat microbes,” with the unfortunate implication that weight gain was the result of some kind of infection to be eradicated.
This new interest in our previously ignored “nation within” is also generating interest in more obscure research. This week, for instance, The New York Times reported on a paper published in the December issue of the Journal of Clinical Pharmacy and Therapeutics. In it, University of Arkansas graduate student Laura Hill reports how a 10-day course of the so-called “cold-busting” herb echinacea produced a dramatic shift in the intestinal microflora of 15 volunteers--boosting the concentration of aerobic, or air-breathing bacteria (normally a tiny portion of our intestinal flora), as well as that of the Bacteroides group in general and Bacteroides fragilis in particular.
While a normal part of a health intestinal microflora, a high concentration of Bacteroides has been associated with elevated risk of colon cancer, Hill points out, while certain strains of B. fragilis may contribute to inflammatory bowel disease in those predisposed to the condition.
Hill and her professor, UA food scientist Jerald Foote, express alarm over the finding that just 10 days on echinacea produced a significant shift in their volunteers’ microflora, as this herb has long been accepted as safe to use for up to eight weeks. Many people pop a capsule of concentrated extract daily throughout the cold and flu season.
Given our intestinal bacteria’s chief function--helping our bodies break down and absorb a broad variety of plant nutrients--neither Gordon’s findings nor Hall and Foote’s should come as any surprise. After all, every one of us knows all too well how the foods we eat produce profound effects on the microbial activity inside our guts: As babies it made us cry, as teenagers it made us laugh, and as adults, it makes us cringe with embarrassment. I’m talking, of course, about the flatulence that result whenever we feed our hydrogen-producing intestinal bacteria. (Around a third of us likewise host one or more methane-producers.)
The extra calories liberated by these micro-digestive processes have long ensured our species’ survival in lean times. That it’s now being blamed on obesity strikes me as akin to blaming weight gain on having a fully functional stomach.
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