Breaking News
December 19, 2018 - New $1.6 million NIH grant supports study on a gene vital to circadian rhythms
December 19, 2018 - Racial Disparities Seen Among Teens Undergoing Flu Vaccination
December 19, 2018 - To resolve inflammation, location matters
December 19, 2018 - Research identifies new therapeutic target for cancer treatment and tissue regeneration
December 19, 2018 - Energy costs, social isolation contribute to health risk of older adults in extreme weather
December 19, 2018 - Potential combination therapy against rare disease of the bone marrow could improve treatment
December 19, 2018 - Researchers aim to improve cognition, reverse weight gain in schizophrenia
December 19, 2018 - UC San Diego Health offers new DRG stimulation device for phantom limb pain
December 19, 2018 - Study examines relationship between growth restriction and risk of childhood mortality
December 19, 2018 - New study provides insights on increased risk of suicide in young patients visiting ED
December 19, 2018 - AHA: Thyroid Problems Linked to Worsening Heart Failure
December 19, 2018 - World-first coeliac disease vaccine enters Phase 2 trials
December 19, 2018 - RNA sequencing offers novel insights into the microbiome
December 19, 2018 - A promising, effective vaccine for common respiratory disease
December 19, 2018 - Protein may slow progression of emphysema, study finds
December 19, 2018 - Studying atrial fibrillation — and exploring new frontiers in precision health
December 19, 2018 - A New Way To Get College Students Through A Psychiatric Crisis — And Back To School
December 19, 2018 - Optum, UnitedHealthcare take action to help people affected by North Carolina winter storms
December 18, 2018 - Weight change in middle-aged, elderly Chinese Singaporeans related to increased risk of death
December 18, 2018 - Immune cells sacrifice themselves to protect us from invading bacteria
December 18, 2018 - Watching brain cells fire, with a twist of gravitational waves
December 18, 2018 - 2018 in Review
December 18, 2018 - Getting the Most Out of the CLARITY Technique
December 18, 2018 - NVF shoes provide a viable option for track and road racing
December 18, 2018 - CRISPR may restore effectiveness of chemotherapies used to treat lung cancer
December 18, 2018 - New app accurately measures and charts progression of skin wounds
December 18, 2018 - Persistent Discrimination ID’d Among Physician Mothers
December 18, 2018 - Cellphone technology developed to detect HIV
December 18, 2018 - A Stanford doctor hits the field with the 49ers — as their airway management physician
December 18, 2018 - The Rise of Anxiety Baking
December 18, 2018 - Just one night of sleep deprivation increases the urge to eat
December 18, 2018 - Study reveals mechanism behind failed remyelination in MS
December 18, 2018 - New genetic testing method increases the precision of biomarker analysis
December 18, 2018 - Simple technique to effectively treat underdiagnosed cause of debilitating chest pain
December 18, 2018 - Barbershop-based medical intervention can successfully lower blood pressure, new data shows
December 18, 2018 - Food labels have caused changes in consumers’ intake and industry’s use of key additives
December 18, 2018 - Sickest children could benefit from split liver transplants
December 18, 2018 - Scientists create patient-specific model to identify most effective treatment for appendix cancer
December 18, 2018 - ‘Little Foot’ endocast reveals a small brain combining ape-like and human-like features
December 18, 2018 - New therapy for childhood blindness shows ‘very promising’ results
December 18, 2018 - Researchers discover promising new compound against Buruli ulcer
December 18, 2018 - Study finds significant use of traditional, complementary and alternative medicines in Sub-Saharan Africa
December 18, 2018 - California Farm Implicated in Outbreak of E. coli Tied to Romaine Lettuce
December 18, 2018 - Mobile health has power to transform HIV/AIDS nursing
December 18, 2018 - Celiac Vaccine in Clinical Trials at Columbia
December 18, 2018 - Research into mental health first aid prompts practical guidance and resources for workplace
December 18, 2018 - Researcher conducts study to investigate peripheral blood markers of Alzheimer’s disease
December 18, 2018 - Researchers identify link between mucus in the small airways and pulmonary fibrosis
December 18, 2018 - EU Commission’s Health Policy Platform to host EKHA program on transplantation
December 18, 2018 - Survivors of childhood Hodgkin lymphoma have high risk of developing solid tumors
December 18, 2018 - Small changes to cafeteria design can get kids to eat healthier, new assessment tool finds
December 18, 2018 - From Machines to Cyclic Compounds
December 18, 2018 - New study reveals best assessment tools to establish delirium severity
December 18, 2018 - Rice University scientists develop synthetic protein switches to control electron flow
December 18, 2018 - Home-based pulmonary function monitoring for teens with Duchenne muscular dystrophy
December 18, 2018 - Researchers identify potential target for new breast cancer treatments
December 18, 2018 - National Biofilms Innovation Centre award grant to Neem Biotech for novel anti-biofilm drug development
December 18, 2018 - Artificial intelligence and the future of medicine
December 18, 2018 - Montana State doctoral student receives grant for her work to improve neuroscience tool
December 18, 2018 - Early postpartum initiation of opioids associated with persistent use
December 18, 2018 - Russian scientists identify molecular ‘switch’ that could be target for treatment of allergic asthma
December 18, 2018 - Surgeons make more mistakes in the operating room during stressful moments, shows study
December 18, 2018 - Immune cells explode themselves to inform about the danger of invading bacteria
December 18, 2018 - Malnutrition in children with Crohn’s disease linked with increased risk of surgical complications
December 18, 2018 - FDA Approves Motegrity (prucalopride) for Adults with Chronic Idiopathic Constipation (CIC)
December 18, 2018 - The long and short of CDK12
December 18, 2018 - Hologic’s Cynosure division introduces TempSure Surgical RF technology in North America
December 18, 2018 - CMR Surgical partners with Nicholson Center to launch U.S.-based training program for Versius
December 18, 2018 - Findings reinforce guidelines for cautious use of antipsychotics in younger populations
December 18, 2018 - Study finds new strains of hepatitis C virus in sub-Saharan Africa
December 18, 2018 - New battery-free, implantable device aids weight loss
December 18, 2018 - Parental alcohol use disorder associated with offspring marital outcomes
December 18, 2018 - Novel Breast Imaging Technique Might Cut Unnecessary Biopsies
December 18, 2018 - What can a snowflake teach us about how cancer spreads in the body?
December 18, 2018 - Management of nausea and vomiting in pregnancy costs the NHS more than previously thought
December 18, 2018 - Green leafy vegetables may reduce risk of developing liver steatosis
December 18, 2018 - Veganism linked to nutrient deficiencies and malnutrition if not planned correctly
December 18, 2018 - Coming Soon: A Tiny Robot You Swallow to Help You Stay Healthy
December 18, 2018 - Modified malaria drug proven effective at inhibiting Ebola
December 18, 2018 - Study finds epigenetic differences in the brains of individuals with schizophrenia
Nosopharm and UIC reveal pharmacology of new class of antibiotics to combat drug resistance

Nosopharm and UIC reveal pharmacology of new class of antibiotics to combat drug resistance

image_pdfDownload PDFimage_print

Nosopharm, a company dedicated to the research and development of new anti-infective drugs, and the University of Illinois at Chicago (UIC) today announce the publication of a study in Molecular Cell on the mechanism of action of odilorhabdins, a new class of antibiotics to combat antibiotic resistance.

The antibiotic, first identified by Nosopharm, is unique and promising on two fronts: its unconventional source and its distinct way of killing bacteria, both of which suggest the compound may be effective at treating drug-resistant or hard to treat bacterial infections.

Called odilorhabdins, or ODLs, the antibiotics are produced by symbiotic bacteria found in soil-dwelling nematode worms that colonize insects for food. The bacteria help to kill the insect and, importantly, secrete the antibiotic to keep competing bacteria away. Until now, these nematode-associated bacteria and the antibiotics they make have been largely understudied.

The odilorhabdin program was launched by Nosopharm in 2011. To identify the antibiotic, Nosopharm’s researchers team screened eighty cultured strains of the bacteria for antimicrobial activity. They then isolated the active compounds, studied their chemical structures and their structure-activity relationships, investigated their pharmacology and engineered more potent derivatives.

The study, published in Molecular Cell, describes the new antibiotic and, for the first time, how it works. Nosopharm’s Maxime Gualtieri, UIC’s Alexander Mankin and Yury Polikanov are corresponding authors on the study and led the research on the antibiotic’s mechanism of action. They found that ODLs act on the ribosome – the molecular machine of individual cells that makes the proteins it needs to function – of bacterial cells.

“Novel classes of antibiotics like the odilorhabdins are very difficult to discover, but then very interesting to investigate”, said Maxime Gualtieri, co-founder and chief scientific officer of Nosopharm. “Our research at Nosopharm is focused on the understanding of the pharmacology of this new class, and the elucidation of their mode of action is a part of this work. We accumulated several early evidences that the bacterial translation was the target of the ODLs. At this point, we needed complementary scientific expertise to investigate much more in detail the mechanism of action of the molecules. This was the purpose of our collaboration with the UIC.”

“Like many clinically-useful antibiotics, ODLs work by targeting the ribosome,” said Yury Polikanov, assistant professor of biological sciences in the UIC College of Liberal Arts and Sciences, “But ODLs are unique because they bind to a place on the ribosome that has never been used by other known antibiotics.”

“When ODLs are introduced to the bacterial cells, they impact the reading ability of the ribosome and cause the ribosome to make mistakes when it creates new proteins,” said Alexander Mankin, director of the Center for Biomolecular Sciences in the UIC College of Pharmacy. “This miscoding corrupts the cell with flawed proteins and causes the bacterial cell to die.”

While many antibiotics can slow bacterial growth, Mankin says antibiotics that actually kill bacteria, called bactericidal antibiotics, are rare.  

“The bactericidal mechanism of ODLs and the fact that they bind to a site on the ribosome not exploited by any known antibiotic are very strong indicators that ODLs have the potential to treat infections that are unresponsive to other antibiotics,” said Mankin, who is also professor of medicinal chemistry and pharmacognosy in the UIC College of Pharmacy.

According to the World Health Organization, antimicrobial resistance is one of the biggest threats to global health today and a significant contributor to longer hospital stays, higher medical costs and increased mortality.

In France, the Nosopharm researchers tested the ODL compounds against bacterial pathogens, including many known to develop resistance.

“We found that the ODL compounds cured mice infected with several pathogenic bacteria and demonstrated activity against both Gram-negative and Gram-positive pathogens, notably including carbapenem-resistant Enterobacteriacae,” said co-corresponding author Maxime Gualtieri, co-founder and chief scientific officer of Nosopharm.

Carbapenem-resistant Enterobacteriacae, or CRE, are a family of germs that have high levels of resistance to antibiotics. One study suggests that CRE, which are the common culprits in bloodstream and surgical site infections, contribute to death in up to 50 percent of patients who become infected.

The researchers say this study is a testament to the growing trend of international and cross-disciplinary collaboration, which is needed to combat the growing and global threat of antibiotic resistance.

“As a biotech company, Nosopharm has to focus on the pharmaceutical development of the ODLs,” said Philippe Villain-Guillot, co-founder and chief executive officer of Nosopharm. “Collaborations with academia with renown expertise in antibiotics like the UIC team help us for this preclinical development and add credibility to the research”.

NOSO-502, the first clinical candidate of the odilhorhabdins, is the most advanced molecule in Nosopharm’s portfolio. The company plans to begin the first clinical trials in humans in 2020.

Source:

ANTIBIOTIC RESISTANCE : NOSOPHARM AND THE UNIVERSITY OF ILLINOIS AT CHICAGO DESCRIBE MECHANISM OF ACTION OF NEW CLASS OF ANTIBIOTICS IN MOLECULAR CELL

About author

Related Articles