Breaking News
February 20, 2019 - Newly licensed nurses work for long hours, also have a second paid job
February 20, 2019 - Physicists identify simple mechanism used by deadly bacteria to fend off antibiotics
February 20, 2019 - FDA Grants Priority Review to Genentech’s Personalized Medicine Entrectinib
February 20, 2019 - Exposure to chemicals before and after birth is associated with a decrease in lung function
February 20, 2019 - Neuroscientists reveal that simple brain region can guide complex feats of mental activity
February 20, 2019 - Study finds new link between food allergies and multiple sclerosis
February 20, 2019 - First gene therapy operation for macular degeneration is a success
February 20, 2019 - Physicians graduated outside the U.S. offer better care for Medicare patients with complex needs
February 20, 2019 - FDA Approves Keytruda (pembrolizumab) for the Adjuvant Treatment of Patients with Melanoma with Involvement of Lymph Node(s) Following Complete Resection
February 20, 2019 - Study identifies brain cells that modulate behavioral response to threats
February 20, 2019 - Researchers take closer look at how viruses bind cells and cause infection
February 20, 2019 - Newly developed gene therapy helps decelerate aging process
February 20, 2019 - Study suggests new treatment strategy for deadly brain cancer
February 20, 2019 - Scientists develop unique hybrid implant that imitates bone structure
February 20, 2019 - Push-ups can be tailored to meet specific needs of individuals
February 20, 2019 - CVD Does Not Modify Depression-Mortality Link in Elderly
February 20, 2019 - Electrical activity early in fruit flies’ brain development could shed light on how neurons wire the brain
February 20, 2019 - Machine learning technique helps predict which asthma patients respond to corticosteroid therapy
February 20, 2019 - Self-reported sleep duration is a useful tool to measure sleep in children, study suggests
February 20, 2019 - T-cells play key role in how the body fights follicular lymphoma
February 20, 2019 - Study shows how 3D organization of genetic material helps perpetuate the species
February 20, 2019 - Researchers engineer stem cell with ‘suicide genes’ to induce cell death in all but beta cells
February 20, 2019 - Study reveals major sex differences in management of cardiovascular risk factors among U.S. adults
February 20, 2019 - Health Tip: Get Your Child to School on Time
February 20, 2019 - Shortcut strategy for screening compounds with clinical potentials for drug development
February 20, 2019 - Common acid reflux drugs tied to elevated risk for kidney disease
February 20, 2019 - Microbiome could be culprit when good drugs do harm
February 20, 2019 - Prenatal exposure to forest fires causes stunted growth in children
February 20, 2019 - Gene therapy restores hearing in mice with congenital genetic deafness
February 20, 2019 - First molecular test predicts treatment response for kidney cancer
February 20, 2019 - New method for improved visualization of single-cell RNA- sequencing data
February 20, 2019 - Researchers capture altered brain activity patterns of Parkinson’s in mice
February 20, 2019 - A possible blood test for detecting Alzheimer’s disease before symptoms show
February 20, 2019 - Primary care physicians associated with longevity, new research finds
February 19, 2019 - New study identifies many key lessons to establish sanctioned safe consumption sites
February 19, 2019 - Single CRISPR treatment can safely and stably correct genetic disease
February 19, 2019 - Multinational initiative to study familial primary distal renal tubular acidosis
February 19, 2019 - Breakthrough study highlights the promise of cell therapies for muscular dystrophy
February 19, 2019 - Subsymptom Threshold Exercise Speeds Concussion Recovery
February 19, 2019 - Midline venous catheters – infants: MedlinePlus Medical Encyclopedia
February 19, 2019 - Searching for side effects
February 19, 2019 - Humanity is all right, probably, although human extinction remains quite possible, researcher says
February 19, 2019 - Having Anesthesia Once as a Baby Does Not Cause Learning Disabilities, New Research Shows
February 19, 2019 - Anti-cancer immunotherapy could be used to fight HIV
February 19, 2019 - Customized Micropatterning for Improved Physiological Relevance
February 19, 2019 - Unique gene therapy approach paves new way to tackle rare, inherited diseases
February 19, 2019 - Activating gene that helps excite neurons reverses depression in male mice
February 19, 2019 - Science Puzzling Out Differences in Gut Bacteria Around the World
February 19, 2019 - Cells that destroy the intestine
February 19, 2019 - On recovery, vulnerability and ritual: An exhibit in white
February 19, 2019 - Scientific Duo Gets Back To Basics To Make Childbirth Safer
February 19, 2019 - COPD patients need more support when understanding new chest symptoms
February 19, 2019 - Using light-based method for production of pharmaceutical molecules
February 19, 2019 - Scientists find link between inflammation and cancer
February 19, 2019 - The High Cost Of Sex: Insurers Often Don’t Pay For Drugs To Treat Problems
February 19, 2019 - Hearing impairment associated with accelerated cognitive decline with age
February 19, 2019 - Researchers identify multiple genetic variants associated with body fat distribution
February 19, 2019 - Influenza and common cold are completely different diseases, study shows
February 19, 2019 - Scientists untangle how microbes manufacture key antibiotic compound
February 19, 2019 - Greater primary care physician supply associated with longer life spans
February 19, 2019 - HIV-1 protein suppresses immune response more broadly than thought
February 19, 2019 - Brain imaging indicates potential success of drug therapy in depressive patients
February 19, 2019 - For 2020 Dem Hopefuls, ‘Medicare-For-All’ Is A Defining Issue, However They Define It
February 19, 2019 - Specialized lung cells appear in the developing fetus much earlier than previously thought
February 19, 2019 - KU professor discusses promise of brain-computer interface to aid, restore communication
February 19, 2019 - Highly effective solution for detecting onset of aggregation in nanoparticles
February 19, 2019 - Early marker of cardiac damage triggered by cancer treatment identified
February 19, 2019 - Antidepressant drug could save people from deadly sepsis, research suggests
February 19, 2019 - CRISPR technology creates pluripotent stem cells that are ‘invisible’ to the immune system
February 19, 2019 - New study establishes how stress favors breast cancer growth and spread
February 19, 2019 - Midlife Systemic Inflammation Linked to Later Cognitive Decline
February 19, 2019 - Therapy derived from parasitic worms downregulates proinflammatory pathways
February 19, 2019 - Antimicrobial reusable coffee cups are less likely to become contaminated with bacteria, study shows
February 19, 2019 - Harnessing the evolutionary games played by cancer cells to advance therapies
February 19, 2019 - AHA News: Heart Transplant Survivor Gets Wedding Proposal at Finish Line
February 19, 2019 - HIV hidden in patients’ cells can now be accurately measured
February 19, 2019 - Research finds reasons for sudden cardiac death in patients with stable ischemic disease
February 19, 2019 - New protocol could help physicians to rule out bacterial infections in infants
February 19, 2019 - Women experiencing miscarriage should be offered treatment choices
February 19, 2019 - New protocol can help identify febrile infants at low risk for serious bacterial infections
New strategy to hinder emergence of antimicrobial-resistant pathogens

New strategy to hinder emergence of antimicrobial-resistant pathogens

image_pdfDownload PDFimage_print

Findings point to possibility of new ‘anti-evolution drugs’ to keep hard-to-treat pathogens from arising

With many disease-causing bacteria ratcheting up their shields against current drugs, new tactics are vital to protect people from treatment-resistant infections.

Lowering mutation rates in harmful bacteria might be an as yet untried way to hinder the emergence of antimicrobial-resistant pathogens. This proposed strategy comes from recent findings in infectious disease research at UW Medicine in Seattle.

The report on this work is published this week in Molecular Cell, one of the journals of Cell Press. The lead author is Mark N. Ragheb, an M.D./Ph.D. student at the University of Washington School of Medicine. The senior researcher is Houra Merrikh, associate professor of microbiology at the UW medical school.

While most efforts against antimicrobial resistance concentrate on producing better antibiotics, the scientists note, “History shows that resistance arises regardless of the nature or potency of new drugs.”

Deaths from antibiotic-resistant infections, they explain, have reached alarming numbers worldwide, and show signs of surpassing mortality from other causes by mid-century.

In looking for another approach to combating this public health threat, the team of microbiologists, genome scientists, pathobiologists and molecular and cellular biologists found evidence for a key promoter of mutations in many different bacteria. This protein factor, DNA translocase Mfd, seems to speed resistance in diverse species toward every antibiotic that was tested.

The researchers call bacterial proteins like Mfd “evolvability factors” because, by increasing mutation rates, they propel the evolution of bacteria. Unlike many multicellular organisms, bacteria evolve quickly. This allows their species to survive or escape suddenly changing conditions, scarcity of nutrients and hostile environments — including attempts to destroy them with antibiotics or immune responses.

Many types of bacteria produce Mfd, an indication of its important physiological role in cells. While it was once thought to assist in DNA repair, cells missing it are not more sensitive to DNA damaging agents. Those with too much of it are actually more prone to DNA damage.

In studying what is behind trimethoprim resistance, for example, the researchers saw that potent, alternative genes that accelerate antibiotic resistance failed to crop up when Mfd was absent. In certain wild type strains of bacteria with Mfd that were studied, those that gained these so called hypermutator alleles had a mutation rate that was more than 1,000 times that of their ancestral strain.

The researchers estimated that roughly half of the strains under study developed hypermutator alleles during the course of becoming resistant to trimethoprim. These strains also accumulated a high number of mutations across their genomes. Strains lacking Mfd were unlikely to form these hypermutator alleles.

The researchers noted, “Generating hypermutation may offer an adaptive strategy to evolve high-level antibiotic resistance, and Mfd might promote this phenomenon.”

In other aspects of their project, the scientists reported that Mfd depends on certain other proteins that work on the bacteria’s genetic machinery in order to carry out its job in antibiotic resistance. Mdf’s role also might possibly be enhanced or even exaggerated during bacterial infections of living things, in comparison to what happens when these bugs live in lab dishes.

Also, the data acquired in this research project seem to show that the role of Mfd in increasing mutations and promoting antibiotic resistance is highly conserved across bacterial species, and is not specific to only a few types of pathogens.

Among the several pathogens studied, the researchers were particularly interested in the mycobacterium that causes tuberculosis. They discovered what they describe as a “striking” difference in resistance to a representative antibiotic — rifampicin — in strains with and without Mfd.

The finding that Mfd is critical to the development of antibiotic resistance in mycobacterium TB could have potential clinical implications, the researchers noted.

Exactly how Mfd encourages mutations and antibiotic resistance is still unclear. One explanation put forth is that it sets the stage for error-prone repair of DNA, even at sites without damage. Or it could interfere with other biochemical pathways for fixing DNA.

The evolutionary assays in this study tried to mimic the variable concentrations of antibiotics that are common during treatment of infections in patients. It’s possible that Mfd may play a role in producing high levels of antibiotic resistance when bacteria are first exposed to antibiotics in amounts that are not enough to stop them.

The researchers also think that Mfd’s ability to promote multiple mutations may be significant in the development of multi-drug resistance.

Based on their findings, the researchers concluded, “We propose that blocking evolvabilty factors, in particular Mfd, could be a revolutionary strategy to address the antimicrobial resistance crisis.”

A new class of anti-evolution drugs that target Mfd or other evolvability factors that promote mutations may complement new antimicrobials and alleviate the problem of chromosomally acquired mutations that leads to antimicrobial resistance.

They added that, in principle, drugs designed to target Mfd could be co-administered with antibiotics during treatment of infections. That might reduce the likelihood of resistance developing at the start of therapy.

Beyond the importance of reducing antibiotic resistance, there could be even wider implications of understanding and intervening in the evolutionary capacity of cells, according to the researchers. These include restraining genetic changes in cancer cells, and limiting the diversity in the strains of a pathogen a person’s immune system is trying to overcome.

Supplemental drugs, such as the proposed evolution inhibitors, could, the researchers predict, improve the efficiency and effectiveness of current treatments, and thereby expand the arsenal of drugs available to combat antimicrobial resistant infections, cancers, and other diseases.

Source:

https://newsroom.uw.edu/news/dodging-antibiotic-resistance-curbing-bacterial-evolution

Tagged with:

About author

Related Articles