Micro in the News

To overcome drug resistance

At the end of April, the WHO released their first, sobering report on antimicrobial resistance across the globe. Dr. Keiji Fukuda, WHO's Assistant Director-General for Health Security warned that: "Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era in which common infections and minor injuries, which have been treatable for decades, can once again kill." The message is of grave concern, but scientists are on it. A recent issue of The Scientist featured four strategies for developing new antibiotics. Some researchers are tweaking the chemical structures of old drugs to make them effective again; some are building cocktails of drugs (the “more power in numbers” approach); others are adding sensitizing agents (adjuvants) to existing drugs; and still others are mining natural environments for entirely new classes of antimicrobials. Check out all the details here.

Engineered yeast chromosome

Synthetic biology and microbiology recently, and officially, collided when scientists from Johns Hopkins University announced the synthesis of an entirely synthetic yeast chromosome. Synthetic biology aims to engineer biological parts, devices, and systems for useful purposes, and the new work moves the field one step closer. The computer-designed, artificial chromosome was inserted into yeast cells...and they lived! One of the ultimate goals of this type of research is to design synthetic microbes that produce any number of materials not found in nature (e.g. synthetic drugs and other beneficial molecules).

Flashback: archaea revealed!

This month, The Scientist published an interesting story about the technique that made possible Carl Woese’s discovery of Domain Archaea. George Fox, professor of biology and biochemistry at the University of Houston, who was a postdoc in the Woese lab at the time of the discovery, argues that if modern sequencing techniques had been used, the archaea would have been missed and would have been classified as “an odd niche of bacteria.”

Chasing a fungal pathogen

mBiosphere recently published a fun profile of June Kwon-Chung, chief of the Molecular Microbiology Section in the Laboratory of Clinical Infectious Disease at NIAID. She has spent the last 40 years hunting, and then trying to understand, a species of the fungus, Cryptococcus, called gattii. While its sister fungus, C. neoformans mostly infects AIDS patients, C. gattii, usually only infects healthy people. It turns out these people aren’t quite as healthy as initially thought, and Kwon-Chung explains why in a recent mBiosphere paper.

Syphilis: then and now

A feature in this month's The Scientist magazine focuses on syphilis and the new approach scientists are taking to understand the origin and evolution of the disease. Syphilis is caused by a corkscrew-shaped bacterium called Treponema pallidum. Although it was first identified in 1905 and antibiotics have effectively controlled the spread of the disease in developed countries, 12 million people are diagnosed with syphilis each year, and in poor countries, this disease is still a major public health concern.

Happy birthday crystallography! 100, wow!

Nature, an international science journal, recently released a special online issue full of news & views, podcasts, and feature articles celebrating 100 years of crystallography. Crystallographers grow molecules into large crystals and expose them to X-rays. As the radiation passes through the crystals, it scatters and forms a diffraction pattern that can be used to determine the structure of the molecule. X-ray crystallography has influenced all areas of science from chemistry to microbiology, from the structure of lysozyme, DNA, and ribosomes to the structure of HIV. Nature’s online feature includes a multimedia history of crystallography, a feature about new powerful x-ray lasers, views on women in crystallography, an argument about the structure of HIV’s anchor molecule (which has implications for vaccine development), and much, much more.

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Neanderthal viruses in modern DNA

Researchers from Oxford University and Plymouth University have discovered ancient human viruses in modern DNA. The scientists compared fossil DNA from Neanderthals and Denisovans to gene sequences from cancer patients and found that the modern DNA shares sequences with the ancient DNA. These sequences belong to a family of viruses called HML2. It is not yet known if these viruses cause cancer or any other disease or are just part of the 90% of “junk” in our DNA. But the scientists are studying the possibility that ancient viruses in human DNA might play a role in the development of diseases like cancer or AIDS.

Syphilis surrogate

How do you study a pathogen you can’t grow in the lab? In a recent news article, Dr. Charles Wolgemuth, University of Arizona Tucson, along with researchers from the University of Connecticut Health Center, experimented with the swimming speeds of both Treponema pallidum (the causative agent of syphilis, which cannot be cultured in the lab) and Borrelia burgdoferi (the bacterium that causes lyme disease) and discovered that they both respond similarly to decreases or increases in the viscosity of the external environment. With this information, they can now use B. burgdoferi, which can be grown in the lab, as a ‘surrogate’ in the study of how T. pallidum moves through organ tissues. The team used mathematical modeling to show how the organism’s flagella react to these changes, which could potentially lead to new methods of treating or preventing these diseases.

New bird flu strain

With the flu season upon us, no one wants to hear about new strains of the flu that can affect humans. However, in a recent news article, scientists describe another strain of bird flu that previously was not thought to infect humans.The 20 year-old woman from Taiwan who was infected with this strain was shortly hospitalized and treated.She was released after they gathered a throat swab for examination.The Taiwan Center for Disease Control identified the strain as the H6N1 strain of bird flu commonly found in chickens around Taiwan. This discovery puts new pressure on scientists to continue to examine flu strains and determine their potential for starting outbreaks of disease in humans.

Ultimate "fitness" program

After 25 years of examination, a bacterial strain that has gone through over 50,000 generations continues to become more “fit” for its simple lab environment.The Michigan State University experiment led by Richard Lenski, is examining if evolution begins to stop in a bacterium if its environment remains constant.Their findings show that there seems to be no “fitness peak” in the near future for their experiment.They have compared hundreds of samples from their self-entitled, “living fossil record” and found that the fitness of their strain continues to climb up a mountain with no peak in sight, so to speak. Although the experiment seems never-ending, it still provides new discoveries regarding evolution and predicting the fitness of future bacterial generations.

HIV in the brain

HIV is responsible for thousands of deaths each year. Although its killing effects are associated with suppression of the immune system, HIV infection can also influence a person’s neurocognitive ability. Scientists at the University of Minnesota recently showed that when the virus infects brain cells, it sheds a protein that alters the synaptic connections between networks of nerve cells. These results explain why nearly 50 percent of all people infected with HIV show some level of neurocognitive impairment. The scientists plan to expand this research and to find or create a drug that will keep this impairment from happening.

Feces-filled pill stops gut infection

Researchers are now one-step closer to treating antibiotic-resistant gut infections using a pill that contains microbes from the feces of healthy human patients. Clostridium difficile, a type of bacterium that causes severe diarrhea and even death, has been one of these tricky infectious microbes to treat. Thomas Louie, an infectious-disease specialist at the University of Calgary in Alberta, Canada, treated 31 patients suffering from C. difficile with the bacterial pills, curing all but one of the patients. Uses of the natural human biota, or microbes naturally found in the human body that do not cause disease, have been used before in hard to treat gut infections, but a fecal transplant is required, usually done through a colonoscopy-like procedure or through a nasal tube that runs directly to the gut. These fecal samples come from healthy human donors. Not all patients can undergo these procedures, however, and a pill containing the healthy microbes could be a step toward curing certain infections. While the results of the bacteria-containing pills have been promising, the pills have been expensive to make due to the finicky nature of the bacteria. Scientists still have extensive work to do before this pill can become commercially available. Image: CDC/Lois S. Wiggs.

More effective leishmaniasis drug tested

Scientists recently reported a new discovery that will improve the effectiveness of a leishmaniasis treatment and make it much cheaper. Leishmaniasis is a parasitic disease that impacts over 12 million people in developing countries, but the treatment costs around $5,000, which is more than most of those people can afford. The current therapy involves a daily dose of amphotericin B for three weeks, and although the current drug is effective, it has some side effects that may cause patients to be hospitalized. The new treatment strategy, which researchers from the University of Miami, Florida and the Universitat Autònoma de Barcelona have tested in mice, employs a nanoparticle called PDD to deliver amphotericin B directly to infected cells. Image: Paulo Henrique Orlandi Mourao.

New effort to treat feline diseases

Two of the most deadly infectious feline viruses will be the targets for a new antiviral study. Researchers in the College of Veterinary Medicine at Kansas State University are working to develop a broad-spectrum antiviral for the coronavirus that causes feline infectious peritonitis (FIP) and the calicivirus that causes virulent systemic feline calicivirus infection (vs-FCV). By studying the structural and functional similarities between the two viruses' proteases, the scientists plan to develop a drug that is effective, safe, and easy to adminster. Image: CDC.

Why there's no cure for the common cold

Every year it’s the same story: we all get the chance to experience the coughing, sneezing, and runny nose of the dreaded common cold. And with all the advancements in science and technology, why is there still no cure for the common cold? A group of scientists led by UW-Madison biochemistry Professor, Ann Palmenberg, are working to answer just that. Palmenberg and her team recently constructed a scrupulous topographical model of the capsid of Rhinovirus C, which is believed to be the cause of close to half of all childhood colds. The virus’s protein shell has recently been determined as quite distinct from that of the A and B strains of Rhinovirus that have long been studied because they're easy to grow in the lab. The ability to create this model has proven itself pivotal in understanding Rhinovirus C, which resists culturing, and up until 2006, had yet to be found lurking within human cells like its A and B siblings. With this ground breaking information, scientists are now one step closer to creating drugs designed to effectively fight against the common cold.

New tech for vaccine development

Professor Stephen Albert Johnston and Joseph Barten Legutki from the Center for Innovations in Medicine at the Biodesign Institute have recently developed a microchip-based technology known as immunosignature diagnosis. This technology was originally developed solely for the early detection of disease, but currently another plausible application is being researched, vaccine evaluation. Testing the effectiveness of a vaccine is of the utmost importance and up until this point has been a fairly lengthy and costly process. Johnston and Legutki tested mouse H1N1, their flu model system, which included seasonal forms of the virus, as well as several commercially available vaccines that had the potential to provide either full or partial protection. They found that different forms of the virus produced different immunosignatures with differing intensities of immune response, but they all contained a “core” immunosignature. These seemingly tiny tidbits of information helped prove that immunosignatures were indeed sensitive enough to detect subtle differences in vaccine formulations and more. With time and testing, Johnston and Legutki hope that immunosignature will be the next big step toward reducing cost and timeframes for vaccine testing and serve as a valuable tool for public health response to pandemic disease.

Combating multidrug-resistant bacteria

It is no secret that as bacteria become resistant to more and more antibiotics, infections become harder and harder to treat. Researchers from the University of Copenhagen and the University of British Columbia have collaborated to formulate a substance, Host Defense Peptidomimetic 4 (HDP-4), that is capable of combating multidrug-resistant microorganisms. Unlike traditional antibiotics, HDP-4 utilizes a multifunctional mechanism, which reduces the chance of a bacterium developing resistance. HDP-4 destabilizes the bacterium's membrane and inserts itself directly into the DNA causing bacterial death. Furthermore, research shows that HDP-4 is linked to the activation of a host’s own immune responses. This research is putting pressure on pharmaceutical companies to invest in projects like these and ultimately help safe thousands of lives a year.

Mapping human HIV resistance

Scientists from France and Switzerland have successfully mapped the entire HIV genome as well as the genome of its victims. The virus mutates up to a million times a day, making it difficult for the host’s immune system to effectively fight back. However, in some individuals the immune system is capable of neutralizing the virus, thus slowing down its replication and destruction rate. It is the genes of these individuals that compelled scientists to determine the specific genetic material necessary for defensive measures against the rapid mutation rate of HIV. This knowledge gives insight into what genetic variations can cause specific types of mutations within the virus. Using the genomes of both victim and virus, there is a possibility of developing drug therapies designed specifically to the patient’s genetics to enhance their strengths and weaknesses in immune responses against HIV.

New technique to enumerate proviral HIV

HIV is a champion at evading the human immune system. One of its strongest defenses is its ability to remain dormant in the body, existing as proviruses. Scientists have recently discovered that these proviruses, while largely inactive, exist in numbers significantly higher than anticipated and possess the ability to become an active form of HIV. Scientists at the Howard Hughes Medical Institute discovered a method with which the population of dormant provirus can be estimated. By activating the T cells and then analyzing the genomes of the proviruses that still remained inactive, scientists were able to determine that of the inactive reservoir, 12% possessed intact genomes that could reactivate and start replication. This 12% tells researchers that the amount of dormant HIV that can cause disease is up to 60 times larger than previously thought. For patients, this discovery means that the inactive proviruses may potentially induce new infection despite successful treatment with antiretrovirals. For researchers, this discovery opens the door for more research into HIV reservoirs and the development of drugs that target the inactive provirus.

Ethnicity influences mouth bacteria

A group of scientists from Ohio State University recently described the bacterial traits that are shared between people with good oral health. While doing the study, they discovered that the bacteria present in someone’s mouth correlates with their ethnicity. By sequencing bacterial DNA from 192 individuals, 398 total bacterial species were discovered. Of these 398, only 8 species were present in every individual, while bacterial species were similar between those with the same ethnicity. The researchers were then able to use this information to predict the ethnicity of an individual. They were able to predict the ethnicity of African-Americans with the best accuracy, followed by Latinos, and then Caucasians. This information may help scientists develop ethnic-specific medical treatments and could play a part in developing a new way to identify individuals.

New hepatitis C drug facing FDA approval

Johnson and Johnson, the company of household product fame, has developed an experimental hepatitis C drug. Simeprevir, the newest in the line for hepatitis C treatment, has proved to be more effective than current hep C treatments. Hepatitis C is a disease that kills 15,000 people a year and another 3 million are infected with the disease in the United States. The original treatment involved a year-long pill and injection series that effectively cured less than half of the patients. Current treatments, developed by Merck and Vertex in 2011, enhanced the effectiveness of the original treatments by bringing the cure rate to between 65 and 75 percent. Johnson and Johnson’s Simeprevir sets this bar even higher with an 80% cure rate when combined with the original treatments. Despite this improved cure rate, the FDA has not yet approved the drug. With some patients experiencing rashes and sunburns while taking Simeprevir, the FDA is awaiting opinions from its expert panel on how to properly label the drug.

Bacteria may trigger MS

Scientists from Weill Cornell Medical College and Rockefeller University have recently identified a possible trigger for Multiple Sclerosis (MS), an autoimmune disease that affects the central nervous system (CNS). The culprit is a bacterium commonly found in soil, Clostridium perfringens. Types B & D of C. perfringens are capable of producing a potent epsilon toxin, which travels via the bloodstream to the brain. Once the toxin reaches the brain, it slows down the CNS's ability to transmit signals, symptoms that are similar to MS. The researchers then studied blood and spinal fluid samples from individuals with and without MS. They found that individuals with MS had epsilon toxin antibodies ten times higher than those without MS, indicating that the people with MS have had more epsilon toxin in their bodies. The researchers were also able to isolate Type B C. perfringens from one individual who reported having a "flare-up" of MS. The scientists are using this discovery to create better treatments and are hopeful that with continuing research they may discover how people with MS were exposed to C. perfringens.

Gene regulation differences between humans and chimpanzees

Chimpanzees and humans have very similar DNA; however, scientists have recently discovered that mRNA expression levels do not reflect differences in protein expression or biological functions between the two. To code for a protein, DNA must first be transcribed into messenger RNA (mRNA), and mRNA has always been used as a standard to determine differences in gene regulation among species. For instance, although humans and chimpanzees have nearly identical genomes, mRNA expression levels are different between the two; therefore, scientists assumed this observation could be extended to differences in protein expression. In the new work, scientists performed studies to test the mRNA expression and found that some mRNA did not lead to changes in protein level in humans versus chimpanzees.These results pose the question of why differences in protein expression do not correlate with differences in mRNA expression perfectly. Scientists believe this study shows that protein expression levels evolve under greater constraint than mRNA levels.

Stem cell transplant repairs damaged gut

Researchers have recently discovered gut stem cells in mice that can repair a type of inflammatory bowel disease.The gut stem cells found in the mouse were different than what was expected. Generally, specialized stem cells are located in tissues throughout the body and are specific for the tissue of origin. Scientists determined they could use these gut stem cells to form mature intestinal tissue. The cells were transplanted into mice with a form of inflammatory bowel disease. The cells successfully repaired the damaged tissue. This experiment has opened many possible avenues of research in humans with inflammatory bowel disease. One key determinant of finding success in humans is whether human cells will respond in the same manner as mouse cells.

Record breaking viruses

Just when scientists thought viruses couldn’t get any bigger or more complex, a group of researchers proved the science world wrong. A new article, published in Science magazine, discusses the
discovery of two new and extremely large viruses, Pandoravirus salinus (isolated from sediments off the coast of Chile) and Pandoravirus dulcis (a freshwater virus isolated from a pond in Australia). Research into giant viruses has been occurring for at least the past ten years since the discovery of Mimivirus and Megavirus chilensis, but the pandoraviruses offer many new genes and features to explore.One novel characteristic of these viruses is that they have almost no genetic relationship to Mimivirus or Megavirus chilensis. Besides this lack of a relationship with other large viruses, only six percent of the proteins coded for by Pandoravirus are similar to other previously identified virus proteins. This study opens the door to biodiversity research in regards to cellular biology and evolution.

A new S. aureus trick

Staphylococcus aureus is a deadly bacterium that can attack the immune system. This microbe kills hundreds of thousands of people every year, but new research by scientists at NYU Langone Medical Center has unlocked a new virulence mechanism employed by this deadly pathogen. Published in the journal, Cell Host and Microbe, the researchers describe how the bacteria release a specialized
toxin that is able to attach to surface receptors of the immune cells called neutrophils. The neutrophils are the body’s first response to invaders, and the system falls apart when these cells are destroyed. The research was also able to show how the variety of toxins that the bacteria release during an infection interact with each other and even stimulate each other. From this information, researchers are also looking into strategies to combat this route of infection as a new tool of defense.

Dormant microbes still repair DNA