Breaking News
December 13, 2018 - Research findings could lead to new targets for cancer-fighting therapeutics
December 13, 2018 - Butantan Institute signs collaboration agreement with MSD to develop dengue vaccines
December 13, 2018 - Study explores how patients want to discuss symptoms with doctors
December 13, 2018 - RUDN medics first to gather scattered data on hepatitis morbidity in Somalia
December 13, 2018 - Age and gender disparities found in use of bed nets to prevent malaria in sub-Saharan Africa
December 13, 2018 - Caffeine therapy benefits developing brains of premature babies
December 13, 2018 - New review focuses on electrospinning techniques used in musculoskeletal tissue engineering
December 13, 2018 - A new division focused on human immune system
December 13, 2018 - Zogenix Announces Positive Phase 3 Trial Results on the Efficacy and Safety of Fintepla (ZX008) in Dravet Syndrome
December 13, 2018 - BCR ABL Genetic Test: MedlinePlus Lab Test Information
December 13, 2018 - Caffeinated beverages during pregnancy linked to lower birth weight babies
December 13, 2018 - Stanford Medicine Health Trends Report examines opportunity to democratize health care
December 13, 2018 - Obsessive-compulsive disorder may protect individuals from obesity
December 13, 2018 - Scientists investigate how a painful event is processed in the brain
December 13, 2018 - Genetic study reveals new insights into underlying causes of moderate-to-severe asthma
December 13, 2018 - Vitamin C supplementation for pregnant smokers may reduce harm to infants’ lungs
December 13, 2018 - New study reveals yin-yang personality of dopamine
December 13, 2018 - Children with high levels of callous traits show widespread differences in brain structure
December 13, 2018 - Long-term Benefit of Steroid Injections for Knee Osteoarthritis Challenged
December 13, 2018 - Adding new channels to the brain remote control
December 13, 2018 - In the Spotlight: A different side of neuroscience
December 13, 2018 - Medical Marvels: Using immunotherapy for melanoma that spread to the brain
December 13, 2018 - Puzzles do not keep dementia away finds study
December 13, 2018 - New mouse model shows potential for rapid identification of promising muscular dystrophy therapies
December 13, 2018 - Study reveals urban and rural differences in prenatal exposure to essential and toxic elements
December 13, 2018 - New collaborative partnership in quest of novel antibiotics
December 13, 2018 - Single tau molecule holds clues to help diagnose neurodegeneration in its earliest stages
December 13, 2018 - AHA Scientific Statement: Low Risk of Side Effects for Statins
December 13, 2018 - What Is Acute Flaccid Myelitis?
December 13, 2018 - How bereaved people control their thoughts without knowing it
December 13, 2018 - Health care democratization underway, according to 2nd annual Stanford Medicine Health Trends Report | News Center
December 13, 2018 - Going Beyond a Single Color
December 13, 2018 - London-based startup launches ‘thedrug.store’ aiming to clean up CBD industry
December 13, 2018 - Loss of tight junction barrier protein results in gastric cancer development
December 13, 2018 - Novel way to efficiently deliver anti-parasitic medicines
December 13, 2018 - RKI publishes new data on disease prevention and utilization of medical services
December 13, 2018 - High-tech, flexible patches sewn into clothes could help to stay warm
December 13, 2018 - The CCA releases three reports on requests for medical assistance in dying
December 13, 2018 - Restoring Hair Growth on Scarred Skin? Mouse Study Could Show the Way
December 13, 2018 - Probiotic use may reduce antibiotic prescriptions, researchers say
December 13, 2018 - Drug repositioning strategy identifies potential new treatments for epilepsy
December 13, 2018 - Chronic rhinitis associated with hospital readmissions for asthma and COPD patients
December 13, 2018 - Food poisoning discovery could save lives
December 13, 2018 - Cloned antibodies show potential to treat, diagnose life-threatening fungal infections
December 13, 2018 - Exercise may reduce colorectal cancer risk after weight loss
December 13, 2018 - Russian scientists create hardware-information system for brain disorders treatment
December 13, 2018 - Moderate alcohol consumption linked with lower risk of hospitalization
December 13, 2018 - Nurturing Healthy Neighborhoods | NIH News in Health
December 13, 2018 - Rise in meth and opioid use during pregnancy
December 13, 2018 - Researchers gain new insights into pediatric tumors
December 13, 2018 - FSU study finds racial disparity among adolescents receiving flu vaccine
December 13, 2018 - Study investigates attitudes toward implementation of ‘sex as a biological variable’ policy
December 13, 2018 - Drug cocktail induces cancer cell death by switching off energy supply
December 13, 2018 - Baculovirus virion completely eliminates liver-stage parasites in mouse model
December 13, 2018 - Researchers create noninvasive technology that detects when nerve cells fire
December 13, 2018 - Allen Institute for Immunology to partner with CU Anschutz to understand dynamics of human immune system
December 13, 2018 - Inability to do daily living tasks delays discharge of mental health patients
December 13, 2018 - Treating patients with hypertension induced albuminuria
December 13, 2018 - New substance could improve efficacy of established breast cancer treatments
December 13, 2018 - Scientists develop new stem cell line to study conversion of stem cells into muscle
December 13, 2018 - Re-programming the body’s energy pathway boosts kidney self-repair
December 13, 2018 - Research findings could help improve treatment of anxiety and post-traumatic stress disorders
December 13, 2018 - The Microbiome Movement announce Microbiotica as official industry partner
December 13, 2018 - New study reveals potential benefits of cEEG monitoring for infant ICU patients
December 13, 2018 - Whole-body imaging PET/MRI offers information to guide treatment options for prostate cancer
December 13, 2018 - International investigators fight against the negative campaign on benzodiazepines
December 13, 2018 - Targeting biochemical pathway may lead to new therapies for alleviating symptoms of anxiety disorders
December 13, 2018 - FDA Approves Tolsura (SUBA®-itraconazole capsules) for the Treatment of Certain Fungal Infections
December 13, 2018 - Are scientists studying the wrong kind of mice?
December 13, 2018 - Computer memory: A scientific team builds a virtual model of a key brain region
December 13, 2018 - Visual inspection alone is insufficient to diagnose skin cancer
December 13, 2018 - Paternal grandfather’s access to food associated with grandson’s mortality risk
December 13, 2018 - Our brain senses angry voices in a flash, study shows
December 13, 2018 - PM2.5 Exposure Linked to Asthma Rescue Medication Use
December 13, 2018 - Can’t exercise? A hot bath may help improve inflammation, metabolism, study suggests
December 13, 2018 - Can artificial intelligence help doctors with the human side of medicine?
December 13, 2018 - Virginia Tech and UC San Diego researchers team up to develop nonopioid drug for chronic pain
December 13, 2018 - NIH offers support for HIV care and prevention research in the southern United States
December 12, 2018 - Activating brain region could revive the urge to socialize among opioid addicts
December 12, 2018 - Relationship impairment appears to interfere with seeking mental health treatment in men
Researchers uncover how insect antibiotic targets Gram-negative bacteria

Researchers uncover how insect antibiotic targets Gram-negative bacteria

image_pdfDownload PDFimage_print

An antibiotic called thanatin attacks the way the outer membrane of Gram-negative bacteria is built. Researchers at the University of Zurich have now found out that this happens through a previously unknown mechanism. Thanatin, produced naturally by the spined soldier bug, can therefore be used to develop new classes of antibiotics.

The global emergence of multi-drug resistant bacteria is posing a growing threat to human health and medicine. “Despite huge efforts from academic researchers and pharmaceutical companies, it has proven very difficult to identify effective new bacterial targets for antibiotic discovery,” says John A. Robinson from the Department of Chemistry at UZH. “One of the major challenges is identifying new mechanisms of antibiotic action against dangerous Gram-negative bacteria.” This group of bacteria includes a number of dangerous pathogens, such as Pseudomonas aeruginosa, which causes life-threatening lung infections, and pathogenic Escherichia coli strains.

Elimination of outer protective shield

An interdisciplinary team of chemists and biologists from UZH and ETH Zurich have now uncovered how thanatin – an antibiotic produced naturally by the spined soldier bug Podisus maculiventris – targets Gram-negative bacteria. The insect’s antibiotic prevents the outer membrane of the bacteria from forming – an unprecedented mechanism in an antibiotic. All Gram-negative bacteria have a double cell membrane, with the outer membrane taking on an important defensive function and helping the bacteria to block the entry of potentially toxic molecules into the cell. The outside of this membrane is made up of a protective layer of complex fat-like substances called lipopolysaccharides (LPS), without which the bacteria could not survive.

Focusing on protein-protein interactions

Using state-of-the-art methods, the Zurich researchers succeeded in proving that thanatin disrupts the transport of LPS molecules to the outer membrane. The transport pathway consists of a super-structure of seven different proteins that assemble to form a bridge from the inner membrane across the periplasmic space to the outer membrane. LPS molecules cross this bridge to the cell’s surface, where they form part of the structure of the outer membrane. Thanatin is able to block the protein-protein interactions that are needed to form the bridge. As a result, LPS molecules are prevented from reaching their destination and the biogenesis of the entire outer membrane is inhibited – which is fatal for the bacteria.

New potential clinical candidates

“This is an unprecedented mechanism of action for an antibiotic and immediately suggests ways to develop new molecules as antibiotics targeting dangerous pathogens,” explains Robinson. “This finding shows us a way to develop substances that specifically inhibit protein-protein interactions in bacterial cells.”

This new mechanism is already being used by an industry partner – Polyphor AG in Allschwil near Basel – to develop new potential clinical candidates. The company has a proven track record of success in this area and has recently also developed the antibiotic murepavadin in cooperation with UZH. Murepavadin is currently in phase III clinical tests in patients with life-threatening lung infections caused by Pseudomonas aeruginosa. “Another new antibiotic targeting other Gram-negative pathogens would be a very welcome addition to the new medicines urgently needed for effective antibacterial therapy,” says Robinson.

About author

Related Articles