Breaking News
April 19, 2018 - Detecting diminished dopamine-firing cells inside brain could reveal earliest signs of Alzheimer’s
April 19, 2018 - Case study shows how intravascular ultrasound imaging helps detect acute aortic syndrome
April 19, 2018 - Research reveals new mechanism by which HIV evades the immune system
April 19, 2018 - Nanodisc-delivered cancer treatment helps eliminate tumors
April 19, 2018 - Functional connectivity MRI could help detect brain disorders and diseases
April 19, 2018 - Finding better way to quantify neuropathy symptoms and treatment efficacy
April 19, 2018 - Study examines effectiveness of caregiver education about sickle cell trait
April 19, 2018 - High-resolution images of tumor vasculature using new technology
April 19, 2018 - Lack of sleep may be linked to risk factor for Alzheimer’s disease
April 19, 2018 - Study finds neurotransmitter may play a role in alcohol relapse, addiction
April 19, 2018 - Researchers build molecular networks of calcific aortic valve disease
April 19, 2018 - Researchers develop highly specific apoptosis assay for pharmacodynamic analyses of tumor specimens
April 19, 2018 - Scientists decipher mechanism of chemotherapy induced female infertility
April 19, 2018 - New insight may allow researchers to design drugs that improve immune responses to vaccines
April 19, 2018 - FDA Approves Crysvita (burosumab-twza) for X-Linked Hypophosphatemia
April 19, 2018 - Researchers uncover origin of virus-fighting plasma B cells
April 19, 2018 - Study finds no evidence of lower intelligence in young children who had anesthesia
April 19, 2018 - Baboons break out of research facility briefly
April 19, 2018 - Study shows how deployment time increases risk of suicide attempt in soldiers
April 19, 2018 - Specific odors from malaria infected individuals attract more mosquitoes
April 19, 2018 - FDA Alert: Rhino 69 Extreme 50000 by AMA Wholesale: Recall
April 19, 2018 - Top HIV cure research team refutes major recent results on how to identify HIV persistence
April 19, 2018 - Experts propose new solutions to increase benefit, affordability of targeted cancer medicines
April 19, 2018 - Deficiency of innate immune adaptor TRIF shortens survival time of ALS mice
April 19, 2018 - New machine learning method offers better way to detect heart disease
April 19, 2018 - CNIO researchers determine structure of protein complex related to cell survival
April 19, 2018 - Faith-based diabetes support program launched by UTSA research team
April 19, 2018 - Volumetric Laser Endomicroscopy Helps ID Barrett’s Regions
April 19, 2018 - Engineered cartilage template to heal broken bones
April 19, 2018 - New computational framework accurately predicts drug-drug and drug-food interactions
April 18, 2018 - Some human cancers may be result of evolutionary accidents, research finds
April 18, 2018 - Higher levels of education linked to lower dementia risk in older African Americans
April 18, 2018 - Smoking Puts Blacks at Higher Risk for Heart Failure
April 18, 2018 - Physiotherapist contributes to guidelines for knee cartilage treatment
April 18, 2018 - Researchers use ‘top-down proteomics’ strategy to get new insights into cancer
April 18, 2018 - Physician assistants less likely to accurately diagnose early stage skin cancers
April 18, 2018 - New faster, streamlined method for bowel cancer detection and treatment
April 18, 2018 - Researchers identify new Listeria species in Costa Rica
April 18, 2018 - Novel interactive diagram shows many facets of mild traumatic brain injury
April 18, 2018 - Short sleep linked to obesity in children and adolescents
April 18, 2018 - When weight loss helps with sleep
April 18, 2018 - New mathematical model can predict efficiency of microbiome therapies
April 18, 2018 - People with high LDL cholesterol levels likely to get greater benefits from statins
April 18, 2018 - Listening to music enhances effect of anti-hypertensive drugs
April 18, 2018 - New method could help treat severe epilepsy in the future
April 18, 2018 - Study reveals increased risks for Alzheimer’s, suicide among youth in polluted cities
April 18, 2018 - Obese patients more likely to develop rapid and irregular heart rate
April 18, 2018 - Study may change global guidelines for managing children with uncomplicated fever
April 18, 2018 - Researchers find letter we’ve seen millions of times, yet can’t write
April 18, 2018 - Roswell Park researchers identify driver of cancer-promoting metabolic changes
April 18, 2018 - Study shows connection between early life stress, depression and sleep disturbances
April 18, 2018 - New tool developed to protect women from HIV infection
April 18, 2018 - Tradeshow Talks with HealthSapiens
April 18, 2018 - NYC mice carry deadly bacteria and viruses
April 18, 2018 - FDA Approves Tavalisse (fostamatinib disodium hexahydrate) for Chronic Immune Thrombocytopenia
April 18, 2018 - Doctors curbing first-time prescriptions for opioids
April 18, 2018 - Scientists analyze nanostructure of chicken eggshells
April 18, 2018 - Study finds muscle complications among active young adults with Type 1 diabetes
April 18, 2018 - Young children should be priority for snail fever treatment
April 18, 2018 - One class of diabetes drug not associated with reduced risk of death
April 18, 2018 - Breakthrough microscope revolutionizes live cell imaging of stem cells
April 18, 2018 - Study on arthritis prevalence and trends reveals unexpected findings
April 18, 2018 - Low-Vision Rehab Improves Several Elements of Visual Function
April 18, 2018 - Babies who look like their father at birth are healthier one year later: study
April 18, 2018 - New drug for migraine in the pipeline
April 18, 2018 - Precancerous colon polyps in Lynch syndrome patients display immune activation
April 18, 2018 - Mouse study shows how tungsten accumulates in the bones
April 18, 2018 - Scientists provide insight into how gene associated with autoimmunity contributes to disease
April 18, 2018 - AHA: Rx for Sedentary Kids — Friends and the Great Outdoors
April 18, 2018 - Expert panel reliable and accurate in identifying injuries in young children
April 18, 2018 - Two immune checkpoint inhibitors efficiently block leukemia development in preclinical tests
April 18, 2018 - New automated text messaging service may help combat opioid epidemic
April 18, 2018 - Large ALS-causing protein aggregates protect rather than harm neurons
April 18, 2018 - Older adults in high-quality nursing homes have lower risks for placement in long-term care facilities
April 18, 2018 - Targeting opioid receptor offers relief for chronic itching
April 18, 2018 - PBO long-lasting insecticidal nets found to be effective in reducing malaria prevalence
April 18, 2018 - New study maps links between 625 genes and different chemotherapy treatments
April 18, 2018 - Obesity rates keep rising for U.S. adults
April 18, 2018 - Bacterial ‘gene swapping’ affects emergence and spread of infectious diseases
April 18, 2018 - NSAIDs alone or with acetaminophen better than opioids at easing dental pain

Researchers catch killer cells red-handed in the act of microbial murder

image_pdfDownload PDFimage_print

Immune cells called “killer cells” target bacteria invading the body’s cells, but how do they do this so effectively? Bacteria can quickly evolve resistance against antibiotics, yet it seems they have not so readily been able to evade killer cells. This has caused researchers to become interested in finding out the exact mechanism that killer cells use to destroy bacterial invaders.

Although one way that killer cells can trigger bacterial death is by inflicting oxidative damage, it has not yet been at all understood how killer cells destroy bacteria in environments without oxygen.

Now, for the first time, researchers have caught killer cells red-handed in the act of microbial murder, observing them as they systematically killed three strains of microbes: E. coli and the bacteria responsible for causing Listeria infection and tuberculosis. The process inflicts bacterial cell death regardless of whether the environment contains oxygen or not.

Their findings, published in Cell, reveal that killer cells act methodically, shooting deadly enzymes into bacteria to “program” a complete internal breakdown and cell death.

The researchers, from Boston Children’s Hospital, the Wistar Institute and the University of Michigan (U-M), used an equally systematic approach to make the discovery.

“We took three bacteria that are very different — and to see which proteins were destroyed by killer cells — we measured their protein levels before, during and after they were attacked,” says Judy Lieberman, MD, PhD, of Boston Children’s Program in Cellular and Molecular Medicine (PCMM), who is co-senior author on the study.

Proteins are critical to life because they direct the use of nutrients and production of cellular machinery that bacteria need to survive.

“Each strain of bacteria has about 3,000 proteins and we saw that — in all three bacterial species — about five to 10 percent of those proteins were slashed by the killer cells’ death-inducing enzyme, called granzyme B,” Lieberman says. “If you made a list of the proteins that bacteria absolutely needed to survive, it would be a small list — interestingly, this seems to be identical to granzyme B’s hit list.”

Deadlier than antibiotics

To deliver the fatal blow of granzyme B, killer cells seek out surface markers on the body’s cell surfaces that might indicate a bacterial invader has taken up residence inside the cell. Killer cells then latch onto the infected cell and use an enzyme to create a small pore in the cell’s surface, through which they inject granzyme B. Once granzyme B gets into the cell, it passes into the invading bacterium and essentially destroys critical proteins for cell survival as well as its ribosomes, the pieces of bacteria’s cellular machinery that actually make proteins.

“The bacteria’s ribosomes fall apart and stop functioning,” says Lieberman, also a professor of pediatrics at Harvard Medical School.

It’s as if the bacteria’s internal factory of life not only loses the blueprints for the parts it needs to make, but also suffers a catastrophic mechanical failure of its assembly line.

“By discovering the bacterial proteins that killer cells ‘take out,’ we have identified potential therapeutic targets that could pave the way for a new class of antimicrobial drugs,” Lieberman suggests.

“We have a huge crisis of antibiotic resistance right now in that most drugs that treat diseases like tuberculosis or listeria, or pathogens like E.coli, are not effective,” said Sriram Chandrasekaran, PhD, co-senior author of the study from U-M, in a press release. “So, there is a huge need for figuring out how the immune system does its work. We hope to design a drug that goes after bacteria in a similar way.”

Importantly, no matter how many times the researchers exposed the bacteria to granzyme B, the bacteria did not develop resistance to its fatal attack. It’s possible that the only way bacteria can survive is to camouflage themselves so that killer cells cannot “see” them and shoot granzyme B into them.

Lieberman is now searching for the specific mechanisms by which bacteria might evade killer cells. She’s also investigating how similar “death pathways” take effect in fungi and parasites, such as those that cause malaria.

Source:

https://vector.childrenshospital.org/2017/11/bacteria-microbial-murder-mystery/

Tagged with:

About author

Related Articles