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Posts about bacteria, antibiotics, microbes, and the overuse of antibiotics. See also health care related posts.
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Related: Articles on the overuse of antibiotics - Antibiotic Resistance and You

Potential Antibiotic Alternative to Treat Infection Without Resistance

Researchers at the University of Michigan have found a potential alternative to conventional antibiotics that could fight infection with a reduced risk of antibiotic resistance. Sadly Michigan is another school that is allowing work of those paid for by the citizens of Michigan to be lock away, only due to the wishes of an outdated journal business model instead of supporting open science. The Big Ten seems much more interested in athletic riches than in promoting science. The Big Ten should be ashamed of such anti knowledge behavior and require open science for their schools if they indeed value knowledge.

By using high-throughput screening of a library of small molecules, the team identified a class of compounds that significantly reduced the spread and severity of group A Streptococcus (GAS) bacteria in mice. Their work suggests that the compounds might have therapeutic value in the treatment of strep and similar infections in humans.

“The widespread occurrence of antibiotic resistance among human pathogens is a major public health problem,” said David Ginsburg, a faculty member at LSI, a professor of internal medicine, human genetics, and pediatrics at the U-M Medical School and a Howard Hughes Medical Institute investigator.

Ginsburg led a team that included Scott Larsen, research professor of medicinal chemistry and co-director of the Vahlteich Medicinal Chemistry Core at U-M’s College of Pharmacy, and Hongmin Sun, assistant professor of medicine at the University of Missouri School of Medicine.

Work on this project is continuing at U-M and the University of Missouri, including the preparation of new compounds with improved potency and the filing of patents, Larsen said. Large research schools are also very interested in patents. That is ok, though seems to cloud the pursuit of knowledge too often when too large a focus is on dollars at many schools. But, it seems to put the schools primary focus on dollars; education seems to start to be a minor activity at some of these large schools.

Current antibiotics interfere with critical biological processes in the pathogen to kill it or stop its growth. But at the same time, stronger strains of the harmful bacteria can sometimes resist the treatment and flourish.

An alternate approach is to suppress the virulence of the infection but still allow the bacteria to grow, which means there is no strong selection for strains that are resistant to antibiotics. In a similar experiment at Harvard University, an anti-virulence strategy was successful in protecting mice from cholera.

About 700 million people have symptomatic group A Streptococcus infections around the world each year, and the infection can be fatal. Most doctors prescribe penicillin. The newly identified compounds could work with conventional antibiotics and result in more effective treatment.

Related: full press releaseWhat Happens If the Overuse of Antibiotics Leads to Them No Longer Working?Norway Reduces Infections by Reducing Antibiotic UseNew Family of Antibacterial Agents DiscoveredMany Antibacterial Products May Do More Harm Than GoodAnti-microbial Paint

Microbiologist Develops Mouthwash That Targets Only Harmful Cavity Causing Bacteria

A new mouthwash developed by a microbiologist at the UCLA School of Dentistry is highly successful in targeting the harmful Streptococcus mutans bacteria that is the principal cause tooth decay and cavities.

In a recent clinical study, 12 subjects who rinsed just one time with the experimental mouthwash experienced a nearly complete elimination of the S. mutans bacteria over the entire four-day testing period.

Dental caries, commonly known as tooth decay or cavities, is one of the most common and costly infectious diseases in the United States, affecting more than 50 percent of children and the vast majority of adults aged 18 and older. Americans spend more than $70 billion each year on dental services, with the majority of that amount going toward the treatment of dental caries.

This new mouthwash is the product of nearly a decade of research conducted by Wenyuan Shi, chair of the oral biology section at the UCLA School of Dentistry. Shi developed a new antimicrobial technology called STAMP (specifically targeted anti-microbial peptides) with support from Colgate-Palmolive and from C3-Jian Inc., a company he founded around patent rights he developed at UCLA; the patents were exclusively licensed by UCLA to C3-Jian.

The human body is home to millions of different bacteria, some of which cause diseases such as dental caries but many of which are vital for optimum health. Most common broad-spectrum antibiotics, like conventional mouthwash, indiscriminately kill both benign and harmful pathogenic organisms and only do so for a 12-hour time period.

The overuse of broad-spectrum antibiotics can seriously disrupt the body’s normal ecological balance, rendering humans more susceptible to bacterial, yeast and parasitic infections.

Shi’s Sm STAMP C16G2 investigational drug, tested in the clinical study, acts as a sort of “smart bomb,” eliminating only the harmful bacteria and remaining effective for an extended period.

“With this new antimicrobial technology, we have the prospect of actually wiping out tooth decay in our lifetime,” said Shi, who noted that this work may lay the foundation for developing additional target-specific “smart bomb” antimicrobials to combat other diseases.

Related: full press releaseFalse Teeth For CatsCavity-Fighting LollipopBiologists Identified a New Way in Which Bacteria Hijack Healthy Cells

What Happens If the Overuse of Antibiotics Leads to Them No Longer Working?

Antibiotics have been a miraculous tool to keep up healthy. Like vaccines this full value of this tool is wasted if it is used improperly. Vaccines value is wasted when they are not used enough. Antibiotics lose potency when they are overused. The overuse of anti-biotics on humans is bad (especially the huge amount of just lazy, not scientific use). But the massive overuse in livestock is much worse, it seems to me.

The health system in the USA is broken in a huge way in which it is broken is the failure to address creating systemic behavior that promotes human health and instead just treating illness. It is much better to avoid a situation where we breed super bugs and then try to treat those super bugs that have evolved to be immune to the antibiotics we have to use.

When antibiotics no longer work

While the source of the current salmonella outbreak remains murky, we can reasonably speculate about the genesis of the bug’s drug-resistance: the reportedly endemic overuse of antibiotics by the agricultural industry.

Drugs are given to livestock for multiple reasons. An obvious one is for the treatment of diseases. When livestock are sick, veterinarians administer a significant dosage in hopes of eliminating the animal’s affliction. Another reason is preventative. Animals in close quarters are more susceptible to infection, so farmers will often administer medicine to healthy animals in order to nip anything nasty in the bud. Most controversially, though, members of the agricultural industry use antibiotics for the express purpose of promoting livestock growth.

It’s a well-known, if not entirely intuitive, fact that healthy animals who are fed small, or “sub-therapeutic,” doses of antibiotics will wind up larger than their unmedicated counterparts. In many such cases, these drugs are given to livestock through their feed or water, and without the prescription or oversight of a veterinarian, according to Dr. Gail Hansen, a senior officer at the Pew Campaign on Human Health and Industrial Farming.

An estimated 80 percent of all antibiotics in the U.S. are given to food-producing livestock, according to the FDA. And approximately 83 percent of that medicine is “administered flock- or herd-wide at low levels for non-therapeutic purposes, such as growth promotion and routine disease prevention,” according to a lawsuit filed against the FDA in May. These figures could have very real consequences for public health, because the Catch-22 of this antibiotic abandon is the widespread development of drug-resistant bacteria, colloquially referred to as “super-bugs.”

In 2006, the European Union banned all use of antibiotics on livestock for growth promotion. And the U.S. Senate will consider similar legislation this year. Sen. Dianne Feinstein, D-Calif., reintroduced the “Preservation of Antibiotics for Medical Treatment Act” last month, which would significantly rein in agricultural drug use, and strictly prohibit the application of sub-therapeutic doses of drugs that have benefits for humans.

Still, the agricultural industry disputes data about its use of antibiotics and the rise of super-bugs, and it has aggressively fought efforts to legislate the matter. As a result, it’s hard to tell how far the legislation might proceed.

Related: Antibiotics Too Often Prescribed for Sinus WoesOveruse of Antibiotics (2005)FDA May Make Decision That Will Speed Antibiotic Drug Resistance (2007)

The end of the era of antibiotics

How did this happen? The driving forces are Darwin and human carelessness. Bacteria are constantly evolving, adapting to the changing conditions they face. Antibiotics usually kill bacteria. But sometimes a bacteria will develop a biological defense – particularly if too small a dose is used.

Antibiotics require a prescription in America, but our nation is still very much a part of the problem. Patients routinely demand these drugs, and doctors acquiesce, for respiratory infections and other ailments that will not respond to antibiotics because they are caused by a virus. We use soap with antimicrobial agents when regular soap does equally well. And we allow farmers to feed antibiotics to livestock in horrifying amounts, not to treat illnesses but to make farming more efficient.

The Potential Role of Concentrated Animal Feeding Operations in Infectious Disease Epidemics and Antibiotic Resistance

This working group, which was part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards—Searching for Solutions, considered the state of the science around these issues and concurred with the World Health Organization call for a phasing-out of the use of antimicrobial growth promotants for livestock and fish production. We also agree that all therapeutic antimicrobial agents should be available only by prescription for human and veterinary use.

Antibiotic Resistance in Livestock: More at Risk Than Steak
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Biologists Identified a New Way in Which Bacteria Hijack Healthy Cells

photo of Zhao-Qing Luo and Yunhao Tan

Associate professor of biological sciences Zhao-Qing Luo, foreground, and graduate student Yunhao Tan identified a new way in which bacteria modify healthy cells during infection. Shown on the computer screen are cells infected with a mutant strain of the bacteria Legionella pneumophila used in their research.

Purdue University biologists identified a new way in which bacteria hijack healthy cells during infection, which could provide a target for new antibiotics. Zhao-Qing Luo, the associate professor of biological sciences who led the study, said the team discovered a new enzyme used by the bacterium Legionella pneumophila – which causes Legionnaires’ disease – to control its host cell in order to take up residence.

“Legionnaires’ disease is a severe form of pneumonia, and this finding could lead to the design of a new therapy that saves lives,” Luo said. “At the same time it also provides great insight into a general mechanism of both bacterial infection and cell signaling events in higher organisms including humans.”

Successful infection by Legionella pneumophila requires the delivery of hundreds of proteins into the host cells that alter various functions to turn the naturally hostile environment into one tailor-made for bacterial replication. These proteins tap into existing communication processes within the cells in which an external signal, such as a hormone, triggers a cascade of slight modifications to proteins that eventually turns on a gene that changes the cell’s behavior, he said.

“Pathogens are successful because they know how information in our cells is relayed and they amplify some signals and block others in order to evade the immune system and keep the cell from defending itself,” Luo said. “Despite our understanding of this, we do not know much about how the proteins delivered by the bacteria accomplish this – how they work. This time we were able to pinpoint an enzyme and see how it disrupted and manipulated a specific signaling pathway in order to create a better environment for itself.”

The signaling pathway involved was only recently identified, and the discovery by Luo and graduate student Yunhao Tan also provides a key insight into its process. The signaling pathway involves a new form of protein modification called AMPylation in order to relay instructions to change cell behavior and has been found to be used by almost all organisms, Luo said.

The bacterium affects the host cell’s functions differently during different phases of the infection process, tapping into signaling pathways to turn on and off certain natural cellular activities. SidD stops the AMPylation process four hours after the start of infection in order to reverse an earlier modification that would be detrimental to the cell if left in place, he said.

Read the full press release.

Related: Using Bacteria to Carry Nanoparticles Into CellsDisrupting Bacterial Communication to Thwart ThemScientists Target Bacteria Where They LiveAre you ready for a world without antibiotics?

Are you ready for a world without antibiotics?

Are you ready for a world without antibiotics?

[Professor Tim Walsh] “This is potentially the end. There are no antibiotics in the pipeline that have activity against NDM 1-producing enterobacteriaceae. We have a bleak window of maybe 10 years, where we are going to have to use the antibiotics we have very wisely, but also grapple with the reality that we have nothing to treat these infections with.”

And this is the optimistic view – based on the assumption that drug companies can and will get moving on discovering new antibiotics to throw at the bacterial enemy. Since the 1990s, when pharma found itself twisting and turning down blind alleys, it has not shown a great deal of enthusiasm for difficult antibiotic research. And besides, because, unlike with heart medicines, people take the drugs for a week rather than life, and because resistance means the drugs become useless after a while, there is just not much money in it.

“The emergence of antibiotic resistance is the most eloquent example of Darwin’s principle of evolution that there ever was,” says Livermore. “It is a war of attrition. It is naive to think we can win.”

I have been writing about the huge risks we are talking with our future for years. The careless misuse of antibiotics is very costly (in human lives, in the future). Bacteria pose great risks to us. We need to take antibiotics to fight serious threats. The misuse of antibiotics by doctors, patients, agri-business… is the problem. And we are all living a much riskier future because far to little is being done to reduce the misuse of antibiotics.

More and more antibiotic treatments are losing effectiveness as bacteria evolve resistance. The evolution is accelerated by misuse. This costs lives today, but is likely to costs many thousands and hundreds of thousands and possible more in the next 50 years.

The NDM-1-producing bacteria were highly resistant to all antibiotics except tigecycline and colistin. In some cases, isolates were resistant to all antibiotics. The emergence of NDM-1 positive bacteria is potentially a serious global public health problem as there are few new anti-Gram-negative antibiotics in development and none that are effective against NDM-1.

Related: Antibiotics Breed Superbugs Faster Than ExpectedAntibiotics Too Often Prescribed for Sinus WoesBacteria Race Ahead of DrugsFDA May Make Decision That Will Speed Antibiotic Drug ResistanceRaised Without AntibioticsWaste Treatment Plants Result in Super BacteriaHow Bleach Kills BacteriaCDC Urges Increased Effort to Reduce Drug-Resistant Infections

Antibiotics, Farming and Superbugs

Antibiotics and farming – how superbugs happen

Provocative new research from Boston University’s medical school and department of biomedical engineering now suggests, though, that multi-drug resistance can be acquired in one pass, through a different mutational process triggered by sublethal doses of antibiotics – the same sort of doses that are given to animals on farms.

In earlier work, the authors found that antibiotics attack bacteria not only in the ways they are designed to (the beta-lactams such as methicillin, for instance, interfere with staph’s ability to make new cell walls as the bug reproduces, causing the daughter cells to burst and die), but also in an unexpected way. They stimulate the production of free radicals, oxygen molecules with an extra electron, that bind to and damage the bacteria’s DNA.

That research used lethal doses of antibiotics, and ascertained that the free-radical production killed the bacteria. In the new research, the team uses sublethal doses, and here’s what they find: The same free-radical production doesn’t kill the bacteria, but it acts as a dramatic stimulus to mutation, triggering production of a wide variety of mutations

Related: A radical source of antibiotic resistance…Overuse of AntibioticsBacteria Race Ahead of DrugsRaised Without Antibiotics

Norway Reduces Infections by Reducing Antibiotic Use

Norway conquers infections by cutting use of antibiotics

Twenty-five years ago, Norwegians were also losing their lives to this bacteria. But Norway’s public health system fought back with an aggressive program that made it the most infection-free country in the world. A key part of that program was cutting back severely on the use of antibiotics.

Now a spate of new studies from around the world prove that Norway’s model can be replicated with extraordinary success, and public health experts are saying these deaths — 19,000 in the U.S. each year alone, more than from AIDS — are unnecessary.

“It’s a very sad situation that in some places so many are dying from this, because we have shown here in Norway that Methicillin-resistant Staphylococcus aureus [MRSA] can be controlled, and with not too much effort,” said Jan Hendrik-Binder, Oslo’s MRSA medical advisor. “But you have to take it seriously, you have to give it attention and you must not give up.”

The World Health Organization says antibiotic resistance is one of the leading public health threats on the planet. A six-month investigation by The Associated Press found overuse and misuse of medicines has led to mutations in once curable diseases like tuberculosis and malaria, making them harder and in some cases impossible to treat.

Now, in Norway’s simple solution, there’s a glimmer of hope.

Related: Articles on the Overuse of AntibioticsCDC Urges Increased Effort to Reduce Drug-Resistant InfectionsKilling Germs May Be Hazardous to Your HealthAntibacterial Products May Do More Harm Than Good

Antibiotics Breed Superbugs Faster Than Expected

We continue to endanger ourselves by using antibiotics inappropriately. This is one of many things that happen when the public at large is ignorant about science and ignores scientific evidence. I don’t believe people want to put other people’s lives in danger. But our behavior in the face of the evidence has us doing just that. I believe because we don’t value science rather than because we don’t care about putting others (and ourselves) in danger. Antibiotics Breed Superbugs Faster Than Expected

Bacteria don’t just develop resistance to one drug at a time, but to many — and at accelerated rates. That’s because antibiotics boost bacterial production of free-radical oxygen molecules that damage bacterial DNA. Repairs to the DNA cause widespread mutations, giving bacteria more chances to randomly acquire drug-resistant traits.

Drug resistance is a serious public health concern. According to the federal Centers for Disease Control and Prevention, 70 percent of 1.7 million infections acquired in hospitals every year are resistant to at least one drug. Those infections annually kill 99,000 Americans — more than double the number that die in car crashes.

Drugs that once destroyed almost any bacteria now kill only a few, or don’t work at all. In the case of some drugs, like Cipro, the decline is dramatic: Where in 1999 it worked against 95 percent of E. coli, it treated only 60 percent by 2006. Against lung infection-causing Acinobacter, its effectiveness fell by 70 percent in just four years.

Though drug resistance is ultimately inevitable, conventional wisdom holds that antibiotics consumed at suboptimum doses hasten the process. Bugs that would have succumbed to a larger dose live to multiply, pushing the strain as a whole closer to resistance. That happens when a prescription goes unfinished, or when antibiotics used on farms enter food and water at low levels.

Of the 35 million pounds of antibiotics consumed annually in the United States, 80 percent goes to farm animals. Much of it is used to treat diseases spread by industrial husbandry practices, or simply to accelerate growth. As a result, farms have become giant petri dishes for superbugs, especially multidrug-resistant Staphylococcus aureus, or MRSA, which kills 20,000 Americans every year – more than AIDS.

Alarming cases of farm-based MRSA and other diseases led to a proposed Congressional law restricting the use of agricultural antibiotics. That bill, supported by the American Medical Association and American Public Health Association, is opposed by farm lobbyists and remains stuck in committee.

Related: Antibiotics Too Often Prescribed for Sinus WoesOveruse of AntibioticsDisrupting the Replication of BacteriaWaste Treatment Plants Result in Super BacteriaBacteria Can Transfer Genes to Other Bacteria

Microbes Flourish In Healthy People

Bugs Inside: What Happens When the Microbes That Keep Us Healthy Disappear? by Katherine Harmon

The human body has some 10 trillion human cells—but 10 times that number of microbial cells. So what happens when such an important part of our bodies goes missing?

“Someone who didn’t have their microbes, they’d be naked,” says Martin Blaser, a professor of microbiology and chair of the Department of Medicine at New York University Langone Medical Center in New York City.

Even though it is such an apparently integral and ancient aspect of human health, scientists are still grasping for better ways to study human microbiota—before it changes beyond historical recognition. Borrowing models from outside of medicine has helped many in the field gain a better understanding of this living world within us. “The important concept is about extinctions,” Blaser says. “It’s ecology.”

The first step in understanding these systems is simply taking stock of what archaea, bacteria, fungi, protozoa and viruses are present in healthy individuals. This massive micro undertaking has been ongoing since 2007 through the National Institutes of Health’s (NIH) Human Microbiome Project. So far it has turned up some surprisingly rich data, including genetic sequencing for some 205 of the different genera that live on healthy human skin.

Despite the flood of new data, Foxman laughs when asked if there is any hope for a final report from the Human Microbiome Project any time soon. “This is the very, very beginning,” she says, comparing this project with the NIH’s Human Genome Project, which jump-started a barrage of new genetic research. “There are basic, basic questions that we don’t know the answers to,” she says, such as how different microbiota are between random individuals or family members; how much microbiota change over time; or how related the microbiota are to each other on or inside a person’s body.

Related: Microcosm by Carl ZimmerTracking the Ecosystem Within UsAlligator Blood Provides Strong Resistance to Bacteria and VirusesBeneficial Bacteria

Disrupting Bacterial Communication to Thwart Them

Interrupting Bacterial Chatter to Thwart Infection

To measure their own numbers, bacteria produce, release, and detect chemical signals called autoinducers. As a population of bacteria grows, it releases more autoinducer into its environment. When individuals detect that a threshold level of autoinducer is present, they change their behavior – by releasing a toxin, for example.

Bassler and her colleagues disrupted these lines of communication by interfering with molecules called acyl-homoserine lactone (AHL) autoinducers, which drive quorum sensing among a kind of bacteria known as Gram-negative bacteria. Gram-negative bacteria include Pseudomonas, E. coli and Salmonella, and other disease-causing microbes. In the study, the team focused on Chromobacterium violaceum, which rarely infects human, but can be lethal to other organisms. C. violaceum lends itself to studies of quorum sensing because it produces a readily detected, bright purple dye when it detects that its population has reached a critical mass.

The experiment shows that interfering with quorum sensing may provide an alternative to traditional antibiotics, Bassler says, and circumvent the problem of resistance that antibiotics foster by killing off susceptible bacteria but allowing resistant ones to survive and propagate.

Related: Bacteria Communicate Using a Chemical Language (quorum sensing)Disrupting Bacteria Communication (2007)Electrolyzed Water Replacing Toxic Cleaning SubstancesGram-negative Bacteria Defy Drug Solutions

Bacteria Use Nitric Oxide to Resist Antibiotics

Scientists Discover Mechanism to Make Existing Antibiotics More Effective at Lower Doses

Eliminating this NO[nitric oxide]-mediated bacterial defense renders existing antibiotics more potent at lower, less toxic, doses. With infectious diseases the major cause of death worldwide, the study paves the way for new ways of combating bacteria that have become antibiotic resistant.

NO is a small molecule composed of one atom of oxygen and one of nitrogen. It was known as a toxic gas and air pollutant until 1987, when it was first shown to play a physiological role in mammals, for which a Nobel Prize was later awarded. NO has since been found to take part in an extraordinary range of activities including learning and memory, blood pressure regulation, penile erection, digestion and the fighting of infection and cancer. A few years ago, the Nudler’s group from NYU demonstrated that bacteria mobilize NO to defend against the oxidative stress. The new study from the same group supports the radical idea that many antibiotics cause the oxidative stress in bacteria, often resulting in their death, whereas NO counters this effect. This work suggests scientists could use commercially available inhibitors of NO-synthase, an enzyme producing NO in bacteria and humans, to make antibiotic resistant bacteria like MRSA and ANTHRAX more sensitive to available drugs during acute infection.

The study by Nudler and his colleagues was funded by a 2006 Pioneer Award from the National Institutes of Health in Bethesda, Maryland. The Pioneer Award, a $2.5 million grant over five years, is designed to support individual scientists of exceptional creativity who propose pioneering and possibly transforming approaches to major challenges in biomedical and behavioral research.

Related: Copper Doorknobs and Faucets Kill 95% of SuperbugsHow Bleach Kills BacteriaForeign Cells Outnumber Human Cells in Our BodiesBacteria Survive On All Antibiotic Diet

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