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.

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.

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.

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)

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.

This past month, scientists at Merck’s Rahway, New Jersey, research labs announced their discovery of platensimycin, a chemical that kills Staphylococcus aureus via a new biological target—the bacterial enzyme FabF, crucial in the assembly of the fatty acids that make up a gram-positive bacterium's cell wall.

It’s been four decades since medicine gained a new class of antimicrobial drug, four decades in which standard drugs have driven the rise of once-rare bacterial genes for chopping up, pumping out or otherwise neutralizing them. These genes can now be found in abundance in the bacteria that inhabit not only our hospitals but also our bodies. For good reason, hope for treating drug-resistant infectious diseases has long resided in blind-siding the bugs with something entirely new, something against which no bacterial resistance mechanism has yet been found.

That’s what Merck scientist Jun Wang and colleagues say they have found in platensimycin, a small molecule produced by Streptomyces plantensis, a bacterium they isolated from a clod of South African dirt. S. platensis hails from the same family of soil bacteria that have already supplied us with the bulk of our antibiotic drugs, from streptomycin to daptomycin. [See recent entry, Shovelful of Resistance.]

The good news is that no antibiotic currently in use in either people or livestock has plantensimycin’s novel mode of action. The bad news is that many bacteria now possess the genetic blueprints for efflux pumps, a kind of generic resistance mechanism for expunging a bacterial cell of most anything noxious.

In fact, efflux pumps are just the sort of resistance mechanism switched on by two other antibiotics in the news this past month. Triclosan and triclocarban target another bacteria enzyme involved in fatty acid synthesis, and they can be found in thousands of consumer products including many kinds of soaps, deodorants, and toothpastes.

In the May issue of Environmental Science & Technology, scientists at Johns Hopkins’ Department of Environmental Health Sciences report that 75 percent of the triclocarban Americans rinse down their drains ends up intact in the sewer sludge applied to farm fields. The researchers estimate that this translates into some 200 tons of the antimicrobial and its cousin triclosan being applied to croplands each year. Last year, the same team found triclocarban contaminating every stream tested within miles of their Baltimore campus. The consequence of all this antibiotic in our water and on our croplands? Unknown.

The once-controversial idea that bacteria communicate and cooperate—both within and between species—has become widely accepted thanks to the work of molecular biologists such as Princeton University’s Bonnie Bassler.

Tel Aviv University physicist Eshel Ben Jacob studies one visually stunning result of this phenomenon: the growth patterns bacteria form in response to laboratory-imposes stresses. Ben Jacob subjects his petri-dish colonies to such challenges as borderline starvation and infusions of noxious chemicals, just the kinds of threats that microorganisms must survive in nature. The colors and shading of his images represent artistic license, but the underlying images are of actual colonies of tens of billions of organisms.

In response to Septrin antibiotic, for example, colonies of Paenibacillus dedritiformis bacteria secrete “come-hither” signals that cause their members to drawer closer together and form large vortices. This increases the colony’s ability to dilute the antibiotic with the lubricating fluid secreted by individual microbes. By contrast, when faced with a sparcity of food, the colony reorganizes into narrow, straight branches that maximize contact with the limited nutrients in its environment.

Here’s the link to Ben Jacob’s gallery of images and an introduction to his ideas on the foundation of cognition in bacteria.

For all the media hype, there’s not much an ordinary reader can do, at this point, about bird flu. Unfortunately, the hype--and growing fatigue--with the subject has obscured important news of a more immediate but less-publicized flu threat.

RICKY LANNETTI in classic running form. Photo by Dick Hostrander.

Two winters ago, emergency-room doctors across the country reported a spate of deaths involving rapidly worsening pneumonia in flu-weakened but previously healthy young adults. One of those victims was Ricky Lannetti, the star wide receiver for Lycoming College, in Williamsport, PA, when he died on December 6th, 2003.

“Like sand running through our fingers,” is how the doctors at Williamsport Community Hospital described Ricky’s rapid decline from flu-like symptoms to massive organ failure and death over the course of 12 hours.

Autopsy showed that Ricky died from an overwhelming infection of methicillin-resistant staph aureus, or MRSA, this on the heels of the flu that had been downing students on his campus since they returned from Thanksgiving break.

The CDC’s analysis of the staph that killed Ricky showed it to be the same nasty strain--USA300--that had been making headlines for causing so-called “flesh eating” skin infections among college and pro athletes the previous year.

That same flu season, hospitals in Baltimore saw four eerily similar deaths. Infectious-disease specialist John Francis, of Baltimore’s John Hopkins University, led the team of investigators who made the link between USA300 and influenza.

Doctors have long known, of course, that flu predisposes the frail and immune-compromised to bacterial lung infections, which is why this patient group is at the top of the list for vaccination each season.

Now USA300 staph provides ample reason for the rest of us to get vaccinated. Its genetic tricks include an array of toxins, including one that garrotes the white blood cells that the immune system deploys to attack microbial invaders.

“When this strain of staph ends up in the same body as the influenza virus,” says Francis, “the result is the perfect storm, a one-two punch to the immune system.”

Bear in mind, about a third of us silently harbor one strain of staph or another inside our nostrils without ever realizing it. It's not something doctors try to eradicate because, well, it just pops right back. Or worse, you get rid of a one strain only to pick up a worse one.

Some researchers have suggested that the only way to prevent colonization with a potential killer such as USA300 might be to inoculate people with a relatively harmless strain of staph. (Choose who gets your parking places, as it were.) Something very similar was done in the 1950s and '60s to stop an epidemic of highly virulent staph that was infecting and killing newborns in hospital nurseries around the world. Indeed, there's growing evidence that USA300 may be that same pandemic killer reincarnated in methicillin-resistant form. (more on that later)

Meanwhile, USA300s is rapidly spreading. It is now THE dominant strain in a number of communities across North America, and has begun surfacing in other countries as well. But surveys of its presence—typically done by testing patients coming into hospitals--remain sparse.

So how to protect yourself? Experts in infection control offer a few modest tips such as don't share towels and equipment at the gym. More importantly, though, it's not to late to get a flu shot to protect yourself of the worst-case scenario of potentially deadly co-infection--advice especially important for team athletes and college students, whose close quarters and shared athletic equipment encourage USA300's spread.

Here’s the medical journal report from the Baltimore investigators who connected the influenza-USA300 dots. And here’s a link to the Ricky Lannetti memorial website recently launched by his father. It likewise includes more information on MRSA.