Breaking News
February 19, 2018 - ID Break: Clean Hands, Fewer Abx; $11 Million HIV Cure?; MenB Vax for Kids
February 19, 2018 - Patient exposure to X-rays depends on how dentists are paid
February 19, 2018 - FDA approves first treatment to reduce risk of NSCLC progression
February 19, 2018 - FDA Expands Approval of Imfinzi (durvalumab) to Reduce the Risk of Non-Small Cell Lung Cancer Progressing
February 19, 2018 - D.C. Week: Congress Passes Spending Bill
February 19, 2018 - Heart-muscle patches made with human cells improve heart attack recovery
February 19, 2018 - FDA Approves First Blood Test to Detect Concussions
February 19, 2018 - Survival Bump in Bladder Cancer with Keytruda
February 18, 2018 - Scientists describe the mechanism of heart regeneration in the zebrafish
February 18, 2018 - Scientists uncover the structure of microtubule motor proteins
February 18, 2018 - Light-activated cancer drugs without toxic side effects are closer to becoming reality
February 18, 2018 - Pioneering research could provide novel insight into how genomic information is read
February 18, 2018 - Pearls From: David Putrino, PhD
February 18, 2018 - Researchers uncover how cancer stem cells drive triple-negative breast cancer
February 18, 2018 - Morning Break: Anti-Anti-Vaxxers; Private Piercings Prohibited; A Case for Pelvic Massage
February 18, 2018 - Lower-dose radiation effective, safe for HPV+ head and neck cancer after induction chemo
February 18, 2018 - Specialist residential service for adults with autism opens in Swansea
February 18, 2018 - FDA Moves to Limit Loperamide Doses per Package
February 18, 2018 - Alcohol use disorder – Genetics Home Reference
February 18, 2018 - Autism might be better detected using new two-minute questionnaire
February 18, 2018 - Hand hygiene-intervention practices may reduce risk of infection among nursing home patients
February 18, 2018 - Researchers develop most sophisticated mini-livers to date
February 18, 2018 - Obamacare Helped More Young Women Get Prenatal Care: Study
February 18, 2018 - School-Based Program Fails to Dent Kids’ Obesity
February 18, 2018 - Research compares neural activity in children with and without autism spectrum disorder
February 18, 2018 - Poor fitness levels increase the risk dementia, concludes study
February 18, 2018 - Risk Score May Reveal if Kids are Victims of Ill-Treatment
February 18, 2018 - Adding Folic Acid to Corn Masa Flour May Prevent Birth Defects
February 18, 2018 - Acute treatment suppresses posttraumatic arthritis in ankle injury
February 18, 2018 - A Role for Budesonide in Autoimmune Hepatitis?
February 18, 2018 - Lupus patients exhibit altered cell proteins, a discovery with potential implications for diagnostics
February 18, 2018 - Muscle plays vital role in regulating heat loss from the hands
February 18, 2018 - High-tech brain scans can provide new way to define intelligence
February 18, 2018 - Study reveals the association between ultra-processed foods and cancer
February 18, 2018 - Prescription Opioid Use Tied to Higher Pneumonia Risk
February 18, 2018 - A non-invasive method to detect Alzheimer’s disease
February 18, 2018 - Deletion of specific enzyme leads to improvement in memory and cognitive functions
February 18, 2018 - Amyloid protein may be transmitted through neurosurgical instruments, study suggests
February 18, 2018 - Electric brain signals of males and females show differences
February 18, 2018 - American Heart Association commends McDonald’s for offering healthier menu in kids’ meals
February 18, 2018 - Parents Find Kids’ Weight Report Cards Hard to Swallow
February 18, 2018 - Does a Financial Conflict of Interest Ever Expire?
February 18, 2018 - Exercise can improve Alzheimer’s symptoms
February 18, 2018 - Scientists develop green chemistry method to improve pharmaceutical manufacturing efficiency
February 17, 2018 - ‘A Time Clock to a Tissue Clock’ for Acute Stroke Care
February 17, 2018 - Cancer Care Gets Personal | NIH News in Health
February 17, 2018 - Do more youth use or do youth use more?
February 17, 2018 - Eating faster linked to obesity
February 17, 2018 - Who’s Still Smoking? ACS Report Highlights Most Vulnerable Adults
February 17, 2018 - Study of smoking and genetics illuminates complexities of blood pressure
February 17, 2018 - Study reveals new link between bone cells and blood glucose level
February 17, 2018 - Children with reading challenges may have lower than expected binocular vision test results
February 17, 2018 - Mass Shootings Trigger Change for Emergency Medicine
February 17, 2018 - ECMO helps revive woman thought to be drowned
February 17, 2018 - Learning stress-reducing techniques may benefit people with epilepsy
February 17, 2018 - Shedding Pounds Before Weight-Loss Surgery a Smart Move
February 17, 2018 - FDA Approves New Cystic Fibrosis Drug Combo
February 17, 2018 - Augmented Reality helps surgeons to ‘see through’ tissue and reconnect blood vessels
February 17, 2018 - Emotional state affects operation of the entire brain instead of being restricted to specific regions
February 17, 2018 - Apalutamide Slows Metastasis in Prostate Cancer
February 17, 2018 - Kids’ well visits linked to lower appendicitis complications
February 17, 2018 - New NK cell-based immunotherapy effective against several types of leukemia
February 17, 2018 - Producing Super-Swelled Lyotropic Crystals for Drug Development
February 17, 2018 - Pfizer Receives Breakthrough Therapy Designation from FDA for PF-04965842, an oral JAK1 Inhibitor, for the Treatment of Patients with Moderate-to-Severe Atopic Dermatitis
February 17, 2018 - Molecular Imaging Flags Risk of AAA Rupture
February 17, 2018 - Researchers identify risk factors for sleep apnea during pregnancy
February 17, 2018 - More work required to find the right drug dosage for pediatric patients
February 17, 2018 - Factors ID’d That Predict RA Remission with Etanercept
February 17, 2018 - A handout or a hand up? How we judge others guides how we help others
February 17, 2018 - ACR receives grant to focus on projects that reduce health disparities
February 17, 2018 - Pimavanserin Might Be Safer Alternative to Ease Dementia Psychosis
February 17, 2018 - Risks of Lung Screening Seen Outweighing Benefits in Many with Smoking History
February 17, 2018 - The impact of Hurricane Harvey on pregnant moms
February 17, 2018 - Gene editing tool used to detect cancer
February 17, 2018 - Researchers detail molecular atlas of cells that form brain’s blood vessels
February 17, 2018 - TUM scientists observe formation of myelin sheaths around nerve fibers
February 17, 2018 - Worst Flu Season Yet? | Medpage Today
February 17, 2018 - Finding the root cause of bronchiolitis symptoms
February 17, 2018 - Climbing stairs reduces hypertension and strengthens muscles
February 17, 2018 - Nature paper unveils bacterial division

TUM scientists discover new substance to fight against tuberculosis

image_pdfDownload PDFimage_print

In search of new strategies against life-threatening tuberculosis infections, a team from the Technical University of Munich (TUM), as well as Harvard University and Texas A&M University in the USA have found a new ally. They discovered a substance that interferes with the mycomembrane formation of the bacterium. It is effective even in low concentrations and when combined with known antibiotics their effectiveness is improved by up to 100-fold.

Among the greatest challenges when treating life-threatening tuberculosis infections is the increasing resistance to antibiotics. But the pathogen itself also makes the life of doctors difficult: its dense mycomembrane hampers the effect of many medications. A team of scientists headed by Stephan A. Sieber, Professor of Organic Chemistry at TU Munich, has discovered a substance that perturbs the formation of this membrane significantly.

The mycomembrane of the tuberculosis pathogen Mycobacterium tuberculosis consists of a lipid double layer that encapsulates the cell wall, forming an exterior barrier. Structural hallmarks are mycolic acids, branched beta-hydroxy fatty acids with two long hydrocarbon chains.

The team hypothesizes that similarly structured beta lactones could “mask” themselves as mycolic acid to enter the mycolic acid metabolic pathways and then block the decisive enzymes.

Helpful disrupter

In the context of an extensive search, the interdisciplinary team of scientists hit the bullseye with the beta lactone EZ120. It does indeed inhibit the biosynthesis of the mycomembrane and kills mycobacteria effectively.

Using enzyme assays and mass spectroscopy investigations, Dr. Johannes Lehmann, a researcher at the Chair of Organic Chemistry II at TU Munich, demonstrated during his doctoral work that the new inhibitor blocks especially the enzymes Pks13 and Ag85, which play a key role in the development of mycomembranes.

EZ120 is effective even in low doses, easily passes the mycomembrane and exhibits only low toxicity to human cells. The combined application of this substance with known antibiotics showed a synergistic effect leading to significantly increased effectiveness.”Vancomycin, a common antibiotic, and EZ120 work together very well,” says Prof. Sieber, who heads the Chair of Organic Chemistry II. “When used together, the dose can be reduced over 100-fold.

“The scientists suspect that disrupting the mycomembrane enables antibiotics to enter the bacteria more easily. This is a new mode of action and might be a starting point for novel tuberculosis therapies.​​

Source:

https://www.tum.de/nc/en/about-tum/news/press-releases/detail/article/34383/

Tagged with:

About author

Related Articles