This Sunday, February 12, is Darwin Day—an occasion to recognize the scientific contributions of 19th-century naturalist Charles Darwin. In this video (originally posted on Darwin Day 2016), our own evolutionary geneticist, Dan Janes, answers questions about Darwin and the role of evolution in health and biomedicine.
When I Grow Up…
Gautam Dantas remembers the day in 10th grade when he first wanted to be a scientist. It was the day he had a new biology teacher, a visiting researcher from the U.S. The teacher passionately described his own biochemical studies of how organisms live together in communities. By the end of the class, Dantas had resolved to earn a Ph.D. in biochemistry.
He ended up doing much more—gaining expertise in computational biology, protein design and synthetic biology. He now combines his skills and knowledge in multifaceted research that spans four departments at Washington University in St. Louis. His goal: to better understand and help combat a vital public health threat—drug-resistant bacteria.
“Our motivation is that we are living in the antibiotic era, and antibiotic resistance is getting out of control,” Dantas says. “We have very few new antibiotics we can use, so we’re kind of scrambling [to find new ways to treat bacterial diseases].”
His research focuses on one of the groups most vulnerable to bacterial infections—newborn babies.
According to his lab’s website , the research is “at the interface of microbial genomics, ecology, synthetic biology, and systems biology,” and it aims “to understand, harness, and engineer the biochemical processing potential of microbial communities.” They do it by scrounging around in infant diapers.
Since their introduction in the 1940s, antibiotic drugs have saved countless lives. Simultaneously, they weeded out strains of bacteria easily killed by the drugs, allowing drug-resistant strains to thrive. Every year, at least 2 million people in the U.S. become infected and at least 23,000 die from drug-resistant bacteria, according to the Center for Disease Control and Prevention. Continue reading “The Irresistible Resistome: How Infant Diapers Might Help Combat Antibiotic Resistance (sort of)”
The outside of every cell on Earth—from the cells in your body to single-celled microorganisms—is blanketed with a coat of carbohydrates, or sugar molecules, that extend from the cell surface, branching off and bending as they interface with the extra-cellular space. The specific patterns in which these carbohydrates are arranged serve as an ID code that help cells recognize each other. For example, human liver cells have one pattern, while human red blood cells another. Certain diseases can even alter the pattern of surface carbohydrates, which is one way the body can recognize damaged cells. On foreign cells, including invading bacteria such as Streptococcus pneumoniae, the carbohydrate coat is even more distinct.
Laura Kiessling , a professor of chemistry at the University of Wisconsin, Madison, studies how carbohydrate coats are assembled and how cells use these coats to tell friend from foe. The implications of her research suggest strategies for targeting tumors, fighting diseases of inflammation and, as she discusses in this video, developing new classes of antibiotics.
Scientists have identified a new family of proteins that, like the targets of penicillin, help bacteria build their cell walls. The finding might reveal a new strategy for treating a range of bacterial diseases.
The protein family is nicknamed SEDS, because its members help control the shape, elongation, division and spore formation of bacterial cells. Now researchers have proof that SEDS proteins also play a role in constructing cell walls. This image shows the movement of a molecular machine that contains a SEDS protein as it constructs hoops of bacterial cell wall material.
Any molecule involved in building or maintaining cell walls is of immediate interest as a possible target for antibiotic drugs. That’s because animals, including humans, don’t have cell walls—we have cell membranes instead. So disabling cell walls, which bacteria need to survive, is a good way to kill bacteria without harming patients.
This strategy has worked for the first antibiotic drug, penicillin (and its many derivatives), for some 75 years. Now, many strains of bacteria have evolved to resist penicillins—and other antibiotics—making the drugs less effective.
According to the Centers for Disease Control and Prevention, drug-resistant strains of bacteria infect at least 2 million people, killing more than 20,000 of them in the U.S. every year. Identifying potential new drug targets, like SEDS proteins, is part of a multi-faceted approach to combating drug-resistant bacteria.
Today, February 12, is Darwin Day—an occasion to recognize the scientific contributions of 19th-century naturalist Charles Darwin. In this video, our own evolutionary geneticist, Dan Janes, answers questions about Darwin and the role of evolution in health and biomedicine.
Invasive fungal infections—the kind that infect the bloodstream, lung and brain—are inordinately deadly. A big part of the problem is the lack of drugs that are both effective against the fungi and nontoxic to humans.
The situation might change in the future though, thanks to the work of a multidisciplinary research team led by chemist Martin Burke at the University of Illinois. For years, the team has focused on an antifungal agent called amphotericin B (AmB for short). Although impressively lethal to fungi, AmB is also notoriously toxic to human cells.
Most recently, the research team chemically modified the drug to create compounds that kill fungi, but don’t disrupt human cells. The scientists explain it all in the latest issue of Nature Chemical Biology.
Invasive fungal infections are so intractable because most antifungal drugs aren’t completely effective. Plus, fungi have a tendency to develop resistance to them. AmB is a notable exception. Isolated 50 years ago from Venezuelan dirt, AmB has evaded resistance and remains highly effective. Unfortunately, it causes side effects so debilitating that some doctors call it “ampho-terrible.” At high doses, it is fatal.
For decades, scientists believed that AmB molecules kill fungal cells by forming membrane-piercing pores, or ion channels, through which the cells’ innards leak out. Last year, Burke’s group overturned this well-established concept using evidence from nuclear magnetic resonance, chemistry and cell-based experiments. The researchers showed that AmB molecules assemble outside cells into lattice-like structures. These structures act as powerful sponges, sucking vital lipid molecules, called ergosterol, right out of the fungal cell membrane, destroying the cell. Continue reading “Designing Drugs That Kill Invasive Fungi Without Harming Humans”
When treating infections, the most critical actions are to quash the infection at its site of origin and prevent it from spreading. If allowed to spread to the bloodstream, an infection could result in body-wide inflammation known as sepsis that can cause organ failure and death.
Intra-abdominal infections, most often caused by gut bacteria, can lead to painful inflammation and present a high risk for sepsis. These infections, which include appendicitis, are some of the most common illnesses around the world.
A standard treatment regimen includes surgically removing the original infection and then prescribing antibiotics to keep the infection from coming back and to prevent sepsis. Currently, doctors administer antibiotics until 2 days after the symptoms disappear, for a total of up to 2 weeks.
Like many other researchers, University of Virginia’s Robert Sawyer wondered if treating intra-abdominal infections with shorter antibiotic courses could be just as effective as the standard treatment. To find out, he and a team of researchers from around the country designed the Study to Optimize Peritoneal Infection Therapy (STOP-IT). Continue reading “Preventing Sepsis in Half the Time”
Antibiotics save countless lives and are among the most commonly prescribed drugs. But the bacteria and other microbes they’re designed to eradicate can evolve ways to evade the drugs. This antibiotic resistance, which is on the rise due to an array of factors, can make certain infections difficult—and sometimes impossible—to treat.
Read the Inside Life Science article to learn how scientists are working to combat antibiotic resistance, from efforts to discover potential new antibiotics to studies seeking more effective ways of using existing ones.
In the United States alone, at least 2 million people each year develop serious infections with bacteria that have become resistant to the antibiotics we use to combat them, and about 23,000 die, according to the Centers for Disease Control and Prevention. Antibiotic resistance can turn once-manageable infections into “superbug” diseases that are difficult—and sometimes impossible—to treat.
Scientists funded by the National Institutes of Health are studying many aspects of antibiotic resistance, including how it spreads. Read this Inside Life Science article for just a few research examples and how the work could aid efforts to curb the emergence of resistance.
Drugs that target a single essential protein in a microbial invader can be effective treatments. But the genomes of pathogens—including bacteria, fungi and parasites—mutate rapidly, and resistance can develop if a mutation changes a target protein’s structure. Molecules that interfere with multiple microbial proteins at once have the potential to overcome the growing problem of antimicrobial drug resistance.
Researchers led by Eric Oldfield of the University of Illinois recently explored whether an experimental drug called SQ109, developed to treat tuberculosis (TB), could be tweaked to attack multiple enzymes, as well as to kill different types of microbes. The scientists succeeded in creating several multitarget analogs of SQ109 that were more effective than the original drug at killing their target pathogens in laboratory experiments. These analogs included one compound that was five times more potent against the bacterium that causes TB while also being less toxic to a human cell line tested.
This work was also funded by the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Allergy and Infectious Diseases and the NIH Office of the Director.