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In the News, Microbiology, Public Health, Research

The end of antibiotics? Researchers warn of critical shortages

The end of antibiotics? Researchers warn of critical shortages

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Bacteria spark infection. Antibiotic kills most bacteria. Remaining bacteria evolve resistance. Second antibiotic wipes out all bacteria. Repeat. Repeat until, that is, there are no effective antibiotics, a scenario that looks increasingly likely, according to recent research from the Center for Molecular Discovery at Yale University led by Michael Kinch, PhD. Kinch now leads the Center for Research Innovation in Business at Washington University in St. Louis, which featured his work in a recent article:

The number of antibiotics available for clinical use, Kinch said, has declined to 96 from a peak of 113 in 2000. The rate of withdrawals is double the rate of new introductions, Kinch said. Antibiotics are being withdrawn because they don’t work anymore, because they’re too toxic, or because they’ve been replaced by new versions of the same drug. Introductions are declining because pharmaceutical companies are leaving the business of antibiotic use discovery and development.

Many of the major players like Pfizer, Eli Lilly, AstraZeneca and Bristol-Myers Squibb are no longer developing antibiotics, Kinch wrote in a recent article in Drug Discovery Today. In part, their disinterest is driven by a tight profit window. The drug approval process takes about 11 years, but a patent only provides 20 years of protection, leaving just nine years to recoup development costs, according to Kinch.

As outlined in the Washington University piece, at least two major initiatives are working to reverse this trend. The Infectious Diseases Society of America introduced the 10 x ’20 Initiative to spur efforts to create 10 new antibiotics by 2010. And Britain is sponsoring the Longitude Prize 2014, a £10 million award for a simple test that will quickly determine the type of bacteria causing an infection and therefore the most effective antibiotic.

Previously: Healthy gut bacteria help chicken producers avoid antibiotics, Free online course aims to education about “pressing public health threat” of antibiotic resistance and Side effects of long-term antibiotic use linked to oxidative stress
Photo by CDC Public Health Image Library

Immunology, Microbiology, Public Health, Research

Gut bacteria may influence effectiveness of flu vaccine

Gut bacteria may influence effectiveness of flu vaccine

flu_shotPast research has shown that the microbes living in your gut can dictate how body fat is stored, hormone response and glucose levels in the blood, which can ultimate set the stage for obesity and diabetes. Now new research suggests that the colonies of bacteria in our intestine play an important role in your body’s response to the flu vaccine.

In the study, Emory University immunologist Bali Pulendran, PhD, and colleagues followed up on a unexpected finding in a 2011 paper: the gene that codes for a protein called toll-like receptor 5 (TLR5) was associated with strong vaccine response. Science News reports that in the latest experiment:

[Researchers] gave the flu vaccine to three different groups: mice genetically engineered to lack the gene for TLR5, germ-free mice with no microorganisms in their bodies, and mice that had spent 4 weeks drinking water laced with antibiotics to obliterate most of their microbiome.

Seven days after vaccination, all three groups showed significantly reduced concentrations of vaccine-specific antibodies in their blood—up to an eightfold reduction compared with vaccinated control mice, the group reports online … in Immunity. The reduction was less marked by day 28, as blood antibody levels appeared to rebound. But when the researchers observed the mice lacking Tlr5 on the 85th day after vaccination, their antibodies seemed to have dipped again, suggesting that without this bacterial signaling, the effects of the flu vaccine wane more quickly.

Previously: The earlier the better: Study makes vaccination recommendations for next flu pandemic, Working to create a universal flu vaccine and Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease
Photo by Queen’s University

Applied Biotechnology, In the News, Infectious Disease, Microbiology, Public Safety

How-to manual for making bioweapons found on captured Islamic State computer

Black DeathLast week I came across an article, in the usually somewhat staid magazine Foreign Policy, with this subhead:

Buried in a Dell computer captured in Syria are lessons for making bubonic plague bombs and missives on using weapons of mass destruction.

That got my attention. Just months ago, I’d written my own article on bioterrorism for our newspaper, Inside Stanford Medicine. So I was aware that, packaged properly, contagious one-celled pathogens can wipe out as many people as a hydrogen bomb, or more. Not only are bioweapons inexpensive (they’ve been dubbed “the poor man’s nuke”), but the raw materials that go into them – unlike those used for creating nuclear weapons – are all around us. That very ubiquity, were a bioweapon to be deployed, could make fingering the perp tough.

The focal personality in my ISM article, Stanford emergency-medicine doctor and bioterrorism expert Milana Trounce, MD, had already convinced me that producing bioweapons on the cheap – while certainly no slam-dunk – was also not farfetched. “What used to require hundreds of scientists and big labs can now be accomplished in a garage with a few experts and a relatively small amount of funding, using the know-how freely available on the internet,” she’d said.

This passage in the Foreign Policy article rendered that statement scarily apropos:

The information on the laptop makes clear that its owner is a Tunisian national named Muhammed S. who joined ISIS [which now calls itself "Islamic State"] in Syria and who studied chemistry and physics at two universities in Tunisia’s northeast. Even more disturbing is how he planned to use that education: The ISIS laptop contains a 19-page document in Arabic on how to develop biological weapons and how to weaponize the bubonic plague from infected animals.

I sent Trounce a link to the Foreign Policy article. “There’s a big difference between simply having an infectious disease agent and weaponizing it,” she responded in an email. “However, it wouldn’t be particularly difficult to get experts to help with the weaponization process. The terrorist has a picked a good infectious agent for creating a bioweapon. Plague is designated as a Category A agent along with anthrax, smallpox, tularemia, botulinum, and viral hemorrhagic fevers. The agents on the Category A list pose the highest risk to national security, because they: 1) can be easily disseminated or transmitted from person to person; 2) result in high mortality rates and have the potential for major public-health impact; 3) might cause public panic and social disruption; and 4) require special action for public-health preparedness.”

Islamic State’s interest in weaponizing bubonic plague should be taken seriously. Here’s one reason why (from my ISM article):

In 1347, the Tatars catapulted the bodies of bubonic-plague victims over the defensive walls of the Crimean Black Sea port city now called Feodosia, then a gateway to the Silk Road trade route. That effort apparently succeeded a bit too well. Some of the city’s residents escaped in sailing ships that, alas, were infested with rats. The rats carried fleas. The fleas carried Yersinia pestis, the bacterial pathogen responsible for bubonic plague. The escapees docked in various Italian ports, from which the disease spread northward over the next three years. Thus ensued the Black Death, a scourge that wiped out nearly a third of western Europe’s population.

Previously: Microbial mushroom cloud: How real is the threat of bioterrorism? (Very) and Stanford bioterrorism expert comments on new review of anthrax case
Photo by Les Haines

Autoimmune Disease, Evolution, Immunology, Microbiology, Nutrition, Public Health, Stanford News

Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?

Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?

hunter-gatherer cafe

Our genes have evolved a bit over the last 50,000 years of human evolution, but our diets have evolved a lot. That’s because civilization has transitioned from a hunter-gatherer lifestyle to an agrarian and, more recently and incompletely, to an industrialized one. These days, many of us are living in an information-intensive, symbol-analyzing, button-pushing, fast-food-munching society. This transformation has been accompanied by consequential twists and turns regarding what we eat, and how and when we eat it.

Toss in antibiotics, sedentary lifestyles, and massive improvements in public sanitation and personal hygiene, and now you’re talking about serious shake-ups in how many and which microbes we get exposed to – and how many of which ones wind up inhabiting our gut.

In a review published in Cell Metabolism, Stanford married-microbiologist couple Justin Sonnenburg, PhD, and Erica Sonnenburg, PhD, warn that modern civilization and its dietary contents may be putting our microbial gut communities, and our health, at risk.

[S]tudies in recent years have implicated [dysfunctional gut-bug communities] in a growing list of Western diseases, such as metabolic syndrome, inflammatory bowel disease, and cancer. … The major dietary shifts occurring between the hunter-gatherer lifestyle, early Neolithic farming, and more recently during the Industrial Revolution are reflected in changes in microbial membership within dental tartar of European skeletons throughout these periods. … Traditional societies typically have much lower rates of Western diseases.

Every healthy human harbors an interactive internal ecosystem consisting of something like 1,000 species of intestinal microbes.  As individuals, these resident Lilliputians may be tiny, but what they lack in size they make up in number. Down in the lower part of your large intestine dwell tens of trillions of  single-celled creatures – a good 10 of them for every one of yours. If you could put them all on a scale, they would cumulatively weigh about four pounds. (Your brain weighs three.)

Together they do great things. In a Stanford Medicine article I wrote a few years back, “Caution: Do Not Debug,” I wrote:

The communities of micro-organisms lining or swimming around in our body cavities … work hard for their living. They synthesize biomolecules that manipulate us in ways that are helpful to both them and us. They produce vitamins, repel pathogens, trigger key aspects of our physiological development, educate our immune system, help us digest our food and for the most part get along so well with us and with one other that we forget they’re there.

But when our internal microbes don’t get enough of the right complex carbohydrates (ones we can’t digest and so pass along to our neighbors downstairs), they may be forced to subsist on the fleece of long carbohydrate chains (some call it “mucus”)  lining and guarding the intestinal wall. Weakening that barrier could encourage inflammation.

The Sonnenburgs note that certain types of fatty substances are overwhelmingly the product of carbohydrate fermentation by gut microbes. These substances have been shown to exert numerous anti-inflammatory effects in the body, possibly protecting against asthma and eczema: two allergic conditions whose incidence has soared in developed countries and seems oddly correlated with the degree to which the environment a child grows up in is spotlessly hygienic.

Previously: Joyride: Brief post-antibiotic sugar spike gives pathogens a lift, The future of probiotics and Researchers manipulate microbes in the gut
Photo by geraldbrazell

Global Health, Microbiology, Nutrition, Pediatrics, Research

Malnourished children have young guts

Malnourished children have young guts

Bangladeshi_childrenChildren who grow up malnourished lag behind healthy kids in terms of their height and weight. But a new study finds that they also fall behind in the bacteria in their guts. The findings may explain why weight gains are often temporary, and malnourished children remain underweight compared to healthy children in the long-term.

Babies get their first gut bacteria from their mothers during birth. As they eat new foods, the community that live in the intestines changes and matures throughout the first few years of life. By age three, an “adult” community has taken up residence in the gut, and helps the body to break down food and boost the immune system. But in malnourished children, scarce or low-quality food and infections from poor sanitation result in an underdeveloped bacterial community that looks more like the inhabitants of a young child.

A study by Sathish Subramanian and colleagues published yesterday in Nature finds that children living in a slum in Dhaka, Bangladesh who were treated for malnutrition with nutrient-dense foods, have a temporary improvement in their gut bacteria. But the community will regress back to a younger state months after the therapy stops. The results correlate with observations that nutritional therapy saves lives, but cannot correct problems such as stunted growth, learning disabilities and a weakened immune system.

Initially, the researchers took stool samples from healthy children of a range of ages from the same slum. By looking at the identity of the bacteria from their intestines, the researchers could figure out what types of bacteria live in the gut at different times. They then looked at the bacterial communities from children receiving therapeutic foods to treat malnutrition to determine the “age” of their communities throughout the course of their treatment.

In a commentary on the study, Elizabeth Costello, PhD, and David Relman, MD, researchers in the Department of Microbiology and Immunology at Stanford, compare the gut communities of malnourished children to a degraded environment, such as a clear-cut rainforest that becomes choked with weeds. Just as it is difficult to clear the weeds and restore the original rainforest trees, it is challenging to rehabilitate the gut communities of chronically malnourished children.

“Degraded communities can be resistant or resilient to change, and although host health can be restored, youth cannot,” write Costello and Relman. “Thus, an ounce of prevention is likely to be worth a pound of cure and, as with other types of developmental delays, early intervention may be crucial.”

The study’s authors suggest that monitoring the gut communities of impoverished children may be one way to kept tabs on their health, and to measure if experimental nutritional treatments are working. Just like height or weight, the age of the gut bacterial community may be one way to track a child’s growth and development.

Patricia Waldron is a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Malnourished infants grow into impoverished adults, study shows and Who’s hungry? You can’t tell by looking
Photo by Mark Knobil

Health Policy, Infectious Disease, Microbiology, Public Health, Stanford News

Microbial mushroom cloud: How real is the threat of bioterrorism? (Very)

Microbial mushroom cloud: How real is the threat of bioterrorism? (Very)

Dr. Milana Trounce, M.D. teaches a class on the the risks of bioterror at the Stanford School of Medicine. Photo taken on Monday, April 21, 2014. ( Norbert von der Groeben/ Stanford School of Medicine )

“What if nuclear bombs could reproduce? Get your hands on one today, and in a week’s time you’ve got a few dozen.”

That’s the lead sentence of a feature article I just wrote for Inside Stanford Medicine. The answer is, bombs can’t reproduce. But something just as potentially deadly – and a whole lot easier to come by – can, and does.

What I learned in the course of writing the feature, titled “How contagious pathogens could lead to nuke-level casualties” (I encourage you to take a whack at it), was bracing. Stanford surgeon Milana Trounce, MD, who specializes in emergency medicine, has been teaching a course that pulls together students, faculty and outside experts from government, industry and academia. Her goal is to raise awareness and inspire collaborations on the thorny multidisciplinary problems posed by the very real prospect that somebody, somewhere, could very easily be producing enough killer germs to wipe out huge numbers of people – numbers every bit as large as those we’ve come to fear in the event of a nuclear attack.

Among those I quote in the article are infectious-disease expert David Relman, MD, and biologist/applied physicist Steven Block, PhD, both of whom have sat in on enough closed-door meetings to know that bioterrorism is something we need to take seriously.

Not only do nukes not reproduce. They don’t leap from stranger to stranger, or lurk motionless in midair or on fingertips. Nor can they be fished from soil and streams or cheaply conjured up in a clandestine lab in someone’s basement or backyard.  One teaspoon of the toxin produced by the naturally occurring bacterial pathogen Clostridium botulinum is enough to kill several hundreds of thousands of people. That’s particularly scary when you consider that this toxin – better known by the nickname “Botox” -  is already produced commercially for sale to physicians who inject it into their patients’ eyebrows.

As retired Rear Adm. Ken Bernard, MD, a former special assistant on biosecurity matters to Presidents Bill Clinton and George W. Bush and a guest speaker for Trounce’s Stanford course, put it: “Who can be sure there’s no off-site, illegal production? Suppose a stranger were to say, ‘I want 5 grams — here’s $500,000’?

That’s five grams, as in one teaspoon. As I just mentioned, we’re talking hundreds of thousands of people killed, if this spoonful were to, say, find its way into just the right point in the milk supply chain (the point where loads of milk from numerous scattered farms get stored in huge holding tanks before being parsed out to myriad delivery trucks). That’s pretty stiff competition for a hydrogen bomb. For striking terror into our hearts, the only thing bioweapons lack is branding – nothing tops that mushroom-cloud logo.

Previously: Stanford bioterrorism experts comments on new review of anthrax case and Show explores scientific questions surrounding 2001 anthrax attacks
Photo of Milana Trounce by Norbert von der Groeben

Applied Biotechnology, Bioengineering, Global Health, Microbiology, Science

The pied piper of cool science tools

The pied piper of cool science tools

Kid-scopeWhen Stanford bioengineer Manu Prakash, PhD, and his students set out to solve a challenging global health problem, the first order of business is to have fun.

“We’re a curiosity-driven lab,” says Prakash, as he sits in his office overflowing with toys, gadgets, seashells and insect exoskeletons.

In the last month, Prakash introduced two new cool science tools — a 50-cent paper microscope and a $5 programmable kid’s chemistry set. The response from fellow science lovers, compiled on this Storify page, has been amazing.

Already, 10,000 kids, teachers, health workers and small thinkers from around the globe have signed up to receive build-your-own-microscope kits. Thousands more have sent us e-mails describing the creative ways they’d use a microscope that they could carry around in their back pockets.

For the love of science, here are a few of these inspirational e-mails:

I would love to have one. I’m only in 6th grade but I love science. I hope to visit the moon one day. — Raul

I am an electrical engineer from Kenya and have never used a microscope in all my life. But what I would really like to do is to avail the foldscope to students in a primary school that I am involved in mentoring. This apart from hopefully inspiring them in the wonders of science, would enable the students see the structure of the mosquito proboscis, a malaria-spreading agent in this part of the world. I would also like to look at the roots of mangrove trees and see the structure that enables them to keep sea water salts out. — Macharia Wanyoike

This is brilliant! I am in science and nanotechnology education and my wish is for South African rural children, Namibia, Zimbabwe, Botswana to all have these microscopes! It will be amazing. — Professor Sanette Brits, University of Limpopo, South Africa

waterbearI am studying how magnetic fields at different frequencies affect water bears. They are very difficult to find and it would be great if I had a tool to help me find them that is  portable while searching for them. I have digital motic microscope phase contrast and darkfield microscopes but nothing portable. — Edward W. Verner (Water bear shown to the left.)

I could use it to check if patients have scabies. Or if I were visiting remote monasteries in the Himalayas where they have outbreaks. I’d definitely pack it. For myself I’d use it on nature walks. GREAT ACCOMPLISHMENT for mankind. Congratulations. — Linda Laueeano, RN

Hi! I am a high school student from South Korea. While I was searching for interesting project, I saw your video. It was very amazing and I can’t believe that only one dollar can save hundreds and thousands people who were suffering from malaria and other diseases that can be found by your “foldscope”. I really love to study about your project and I had already read your thesis. Truly, it was hard to understand everything, but I really tried hard and I discussed this issue for more than a week with my science club. We are group of 10 people and we are eager to do this project. Also I really appreciate you to do this wonderful thing for poor kids in many other countries. Thanks. — Joung Yeon Park

I am assisting a K-12 community school with creating a STEAM Innovation Knowledge HUB, as they are trying to move their Common Core Curriculum into a STEM to STEAM driven program. It would be great to receive several Foldscopes or be able to purchase. Please contact me ASAP. Congratulations on a great new support product and great innovation. Thank you, smile. — Dr. Dion N. Johnson, Wayne State University

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Global Health, Immunology, Infectious Disease, Microbiology, Research, Stanford News

Discovered: Why so many people with schistosomiasis (there’s a lot of them) are so vulnerable to bacterial co-infection

Discovered: Why so many people with schistosomiasis (there's a lot of them) are so vulnerable to bacterial co-infection

More than a billion people worldwide – almost all of them in developing countries – are infected by worm-like parasitic organisms called helminths. Organisms making up just a single genus of helminth, Schistosoma, account for one-quarter of those infections, which damage different body parts depending on what schistosomal species is doing the infecting. Some go for the lung. Others (card-carrying members of the species Schistosoma haematobium) head for the urinary tract, with one in ten infected patients suffering severe physical consequences.

People with schistosomiasis of the urinary tract are especially vulnerable to bacterial co-infections. Worse, these co-infections exacerbate an already heightened risk of bladder cancer in infected individuals, it’s believed. Unfortunately, considering the massive numbers of cases, surprisingly little is understood about the molecular aspects of the infection’s course.

A big reason for that relative ignorance has been the absence of an effective animal model enabling the detailed study of urinary-tract schistosomiasis. A couple of years ago, Stanford schistosomiasis expert Mike Hsieh, MD, PhD, developed the world’s first decent mouse model for the disease, allowing him to explore the molecular pathology that occurs early in the course of infection. Now, in a just-published study in Infection and Immunity, Hsieh has put that mouse model to work in coaxing out the cause of the curious collegiality of S. haematobium and co-infecting bacteria.

The secret, the scientists learned, is that S. haemotobium infection induces a spike in levels of a circulating immune-system signaling protein, or cytokine, called IL-4. That excess, in turn, results in a drop in the number and potency of a subset of immune cells that are important in fighting off bacterial infections. The discovery opens a pathway toward the development of new, non-antibiotic drug treatments for co-infected patients that won’t wreak havoc with their microbiomes, as antibiotics typically do.

Previously: Is the worm turning? Early stages of schistosomiasis bladder infection charted, Neglected story of schistosomiasis in Ghana, as told in a  sand animation and A good mouse model for a bad worm

Immunology, Mental Health, Microbiology, Public Health

Examining how microbes may affect mental health

Examining how microbes may affect mental health

Over on the NIH Director’s Blog today, there’s an interesting post about research efforts aimed at determining how the colonies of bacteria in our gut could play a role in mental health. As described in the piece, past research has shown there are a number of ways microbes can influence our thoughts, behavior and mood:

First of all, and perhaps most obviously, gut bacteria are engaged in a wide range of biochemical activities, producing metabolites that are absorbed into the human bloodstream. But there are other connections. One species of bacterium, for example, sends messages that are carried via the vagus nerve, which links the intestinal lining to the brain. When this species is present, the mice demonstrate fewer depressive behaviors than when it’s absent. Another bacterium plays an enormous role in shaping the immune system, which goes awry in many neurological diseases. This species of bacterium interacts directly with the immune system’s regulatory T-cells to provide resistance against a mouse version of multiple sclerosis, a progressive disease in which the immune cells damage the central nervous system by stripping away the insulating covers of nerve cells.

As Stanford microbiologist and immunologist Justin Sonnenburg, PhD, commented in a past entry on Scope, “There’s no doubt about it. These microbes are influencing every aspect of our neurobiology. There’s a direct connection between the microbes inside our gut and the central nervous system. They’re influencing our behavior, our moods, even our decisions.”

Previously: Could gut bacteria play a role in mental health?Study shows probiotic foods may alter metabolism, but can they boost your health? and Study shows intestinal microbes may fall into three distinct categories

Applied Biotechnology, Microbiology, Patient Care, Research, Stanford News, Surgery

Staphylococcus aureus holes up in upper nasal cavity, study shows

Staphylococcus aureus holes up in upper nasal cavity, study shows

nostrilsA posse led by Stanford microbe sleuth and microbiologist David Relman, MD, has apprehended Staphylococcus aureus, one of the most notorious sources of serious infections, lurking in formerly unsuspected nasal hideaways. The discovery may explain why attempts to expunge S. aureus from the bodies of hospitalized patients being readied for surgery often meet with less than perfect results.

About one in three of us are persistent S. aureus carriers, and another third of us are occasional carriers. This bacterial shadow, which abounds on skin (especially the groin and armpits) and is quite at home in the nose, does us no harm most of the time. But if it gets into the bloodstream or internal organs, it can cause life-threatening problems such as sepsis, pneumonia and endocarditis (infection of heart valves). That makes S. aureus not such a good thing to be coated with if you’re about to have your skin punctured by a catheter or pierced by a scalpel.

This is exacerbated by the all-too-frequent presence, particularly in hospital settings, of S. aureus strains resistant to an entire family of antibiotics related to methicillin. In 2011, more than 80,000 severe methicillin-resistant S. aureus infections and more than 11,000 related deaths occurred in the U.S. alone, along with a much higher number of less-severe such infections.

In a study just published in Cell Host & Microbe, Relman – who pioneered the use of ultra-high-volume gene-sequencing techniques to sort out the thousands of species of microbes that communally inhabit our skin, orifices and innards – and his team used this method to show that mucosal sites way up high in our nose, where standard S. aureus-elimination techniques may not reach, can serve as reservoirs for S. aureus. That may, at least in part, explain why efforts to rid patients of this potentially nasty bug have so often fallen short of the mark, as I noted in my news release about the new findings:

Rigorous and somewhat tedious regimens for eliminating S. aureus residing on people’s skin or in their noses do exist, but it’s typically a matter of weeks or months before the bacteria repopulate those who are susceptible. The new study offers a possible reason why this is the case.

Previously: Cultivating the human microbiome, Anti-plaque bacteria: Coming soon to your toothpaste? and Eat a germ, fight an allergy
Photo by OakleyOriginals

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