For Salmonella and many other disease-causing bacteria that find their way into our bodies, infection begins with a poke. That’s because these bad bugs are equipped with a needle-like protein filament that punctures the outer membrane of human cells and then, like a syringe, injects dozens of toxic proteins that help them replicate.
Cammie Lesser at Massachusetts General Hospital and Harvard Medical School, Cambridge, and her colleagues are now on a mission to bioengineer strains of bacteria that don’t cause disease to make these same syringes, called type III secretion systems. The goal is to use such “good” bacteria to deliver therapeutic molecules, rather than toxins, to human cells. Their first target is the gastrointestinal tract, where they hope to knock out hard-to-beat bacterial infections or to relieve the chronic inflammation that comes with inflammatory bowel disease (IBD).
Tags: antibodies, bacteria, bacterial toxins, bioengineering, digestion, drug delivery, drug delivery vehicles, E. coli, Escherichia coli, gastrointestinal tract, IBD, inflammation, inflammatory bowel disease, intestine, microbiology, NIH Director’s 2016 Transformative Research Award, probiotics, secretion system, Shigella, single-domain antibodies, synthetic biology, technology, type III secretion systems
For patients who’ve succeeded in knocking out a bad urinary tract infection (UTI) with antibiotic treatment, it’s frustrating to have that uncomfortable burning sensation flare back up. Researchers are hopeful that this striking work of science and art can help them better understand why severe UTIs leave people at greater risk of subsequent infection, as well as find ways to stop the vicious cycle.
Here you see the bladder (blue) of a laboratory mouse that was re-infected 24 hours earlier with the bacterium Escherichia coli (pink), a common cause of UTIs. White blood cells (yellow) reach out with what appear to be stringy extracellular traps to immobilize and kill the bacteria.
Tags: antibiotic resistance, bladder, bladder infection, chronic inflammation, Cox2, E. coli, Escherichia coli, FASEB Bioart 2016, immunology, inflammation, microbiology, recurrent UTI, urinary tract infection, UTI, white blood cells, women's health
For nearly 20 years, Hao Wu has studied innate immunity, our body’s first line of defense against infection. One of her research specialties is the challenging technique of X-ray crystallography, which she uses to capture the atomic structure of key molecules that drive an inflammatory response. But for this method to work, the proteins have to be coaxed to form regular crystals—and that has often proven to be prohibitively difficult. Wu, now at Boston Children’s Hospital and Harvard Medical School, can be relentless in her attempts to crystallize difficult molecular structures, and this quality has helped her make a number of important discoveries. Among them is the seminal finding that innate immune cells process and internalize signals to handle invading microbes much differently than previously thought.
Innate immune cells, which include macrophages and neutrophils, patrol the body non-specifically, keeping a look out for signs of anything unusual. Using protein receptors displayed on their surfaces, these cells can sense distinctive molecular patterns on microbes, prompting an immediate response at the site of infection.
Wu has shown that these cells form previously unknown protein complexes that mediate the immune response [1, 2]. She received an NIH Director’s 2015 Pioneer Award to help translate her expertise in the structural biology of these signaling complexes into the design of new kinds of anti-inflammatory treatments. This award helps exceptionally creative scientists to pioneer transformative approaches to major challenges in biomedical and behavioral research.
Tags: Alzheimer’s disease, anti-inflammatory treatment, ASC, cell signaling, chronic inflammation, cryo-EM, gout, immune response, immunology, inflammation, innate immunity, lymphoma, NIH Director’s 2015 Pioneer Award, NIH Pioneer Award, signalosome, SMOCs, structural immunology, supramolecular organizing centers, x-ray crystallography
In recent years, scientific evidence has begun to accumulate that indicates taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) on a daily basis may lower the risk of developing colorectal cancer. Now, a new study provides more precise information on who might benefit from this particular prevention strategy, as well as who might not.
Published in the journal JAMA, the latest work shows that, for the majority of people studied, regular use of aspirin or NSAIDs was associated with about a one-third lower risk of developing colorectal cancer. But the international research team, partly funded by NIH, also found that not all regular users of aspirin/NSAIDs reaped such benefits—about 9 percent experienced no reduction in colorectal cancer risk and 4 percent actually appeared to have an increased risk . Was this just coincidence, or might there be a biological explanation?