Breaking News
November 19, 2017 - Researchers identify possible genetic basis for coronary artery disease
November 19, 2017 - Stress experienced by emergency call handlers has negative impact on psychological health
November 18, 2017 - New cancer cell screening is improving childhood leukaemia treatment
November 18, 2017 - Groundbreaking study identifies protein as potential factor in cancer metastasis
November 18, 2017 - New model to test effectiveness of existing and potential CF therapies
November 18, 2017 - Staying Active May Lower Odds for Glaucoma
November 18, 2017 - Potential new autism drug shows promise in mice
November 18, 2017 - Some states roll back ‘retroactive Medicaid,’ a buffer for the poor — and for hospitals
November 18, 2017 - Selectively deleting stem cell factor promotes recovery after TBI in mice
November 18, 2017 - Breakthrough research brings new procedure closer to helping patients with blood cancer
November 18, 2017 - Dr Peter Simpson Appointed to SLAS Board of Directors
November 18, 2017 - Friendships between young children can protect against ADHD
November 18, 2017 - Old World monkeys could hold key to stop progression of rheumatoid arthritis
November 18, 2017 - Harris Health System RNs named among 20 Outstanding Nurses for 2017
November 18, 2017 - Old World monkeys could be key to a new, powerful rheumatoid arthritis therapy
November 18, 2017 - Mount Sinai researchers identify new therapeutic target for ER+ breast cancer
November 18, 2017 - Age, CRP levels predict success in tapering of biologics in rheumatoid arthritis patients
November 18, 2017 - New dye could be used to observe electrical activity of neurons in the brain
November 18, 2017 - New study further validates use of vaginal progesterone to decrease risk of preterm birth
November 18, 2017 - Russian researcher determined range of reference values for boron in the human body
November 18, 2017 - ‘What the Health?’ Tax bill or health bill?
November 18, 2017 - Could Your Cat Give You ‘Bird Flu?’
November 18, 2017 - Vitamin D Linked to Fertility Outcomes in ART
November 18, 2017 - Neuroscientists identify genetic changes in microglia in a mouse model of neurodegeneration and Alzheimer’s disease
November 18, 2017 - Tax reform proposal could impact care for older Americans
November 18, 2017 - PCSK9 inhibitor offers clinical benefit to patients with peripheral artery disease
November 18, 2017 - Researchers receive £1.3 million to develop sight-saving imaging technology
November 18, 2017 - Novel buckypaper sensor could pave way for high-performance, affordable wearable technology
November 18, 2017 - Despite ACA cost protections, most adolescents skip regular checkups
November 18, 2017 - Stem cell treatment allows paraplegic rats to walk and regain sensory perception
November 18, 2017 - HTC analytical conference comes to the UK
November 18, 2017 - Face It: Drinking, Smoking Takes Toll on Looks: MedlinePlus Health News
November 18, 2017 - New research shows where in the brain the earliest signs of Alzheimer’s occur
November 18, 2017 - Philips announces launch of global movement to raise awareness for COPD
November 18, 2017 - University of Bristol awarded grant to reduce antibacterial drug resistance in Thailand
November 18, 2017 - New oxytocin chemical sensor could be first step towards early diagnosis of autism
November 18, 2017 - Study shows how naïve T-cells may affect tumor immunity and immunotherapy
November 18, 2017 - New studies highlight importance of cardiorespiratory fitness to reduce CVD risk
November 18, 2017 - Study finds medical cannabis is effective at reducing opioid addiction
November 18, 2017 - Specially tailored, ultrafast light pulses can trigger neurons to fire in different patterns
November 18, 2017 - Decrease in sunshine linked to rising incidence of Rickets
November 18, 2017 - Harnessing social media big data to fight against prescription drug crisis
November 18, 2017 - Researchers find way to switch tumor cells between 2D and 3D morphology
November 18, 2017 - FDA Approves Hemlibra (emicizumab-kxwh) for Hemophilia A with Inhibitors
November 18, 2017 - Adolescents underreport amphetamine use, likely unaware that adderall is amphetamine
November 18, 2017 - Study reveals a reduced risk of teenage eczema in breastfed babies
November 18, 2017 - Separating side effects could pave way for safe, effective pain medications
November 18, 2017 - Gut bacteria at young age can contribute to MS disease onset and progression, study suggests
November 18, 2017 - Environmental triggers may play role in development of Lupus
November 18, 2017 - Review looks into conventional versus new treatment modalities in orthodontic pain management
November 17, 2017 - FDA Alert: Diphenoxylate Hydrochloride and Atropine Sulfate Tablets by Greenstone: Recall
November 17, 2017 - For older women, every movement matters
November 17, 2017 - Talking-based therapy could transform aftercare for cancer survivors
November 17, 2017 - Olympus IXplore SpinSR10 imaging system enables researchers to observe fine details in live cells
November 17, 2017 - Study explores reasons for underrepresentation of minorities in genetic cancer research
November 17, 2017 - California firm running physician practices is closing down as scrutiny ramps up
November 17, 2017 - BMI not valid measure of obesity in postmenopausal women, study shows
November 17, 2017 - Vaginal progesterone decreases the risk of premature birth in women with short cervix
November 17, 2017 - Pricey ER Tests for Chest Pain Often Unnecessary
November 17, 2017 - ‘Old’ Lungs May Be Good Transplant Options: MedlinePlus Health News
November 17, 2017 - How not to gain weight over the holidays
November 17, 2017 - Researchers map first-ever proteome of healthy human heart
November 17, 2017 - Drug used to prevent and treat malaria may also be effective for Zika virus
November 17, 2017 - One in 20 children still receiving codeine to treat pain despite warning from federal regulators
November 17, 2017 - Improving clinical trials with machine learning
November 17, 2017 - Experts identify mental exercise program that can reduce risk of dementia
November 17, 2017 - Just-in-time 3-D implants set to transform tumor surgery
November 17, 2017 - Skin patch offers hope for people with peanut allergy
November 17, 2017 - Scientists identify biomarkers that predict risk of death in Ebola patients
November 17, 2017 - Heart attack, stroke patients have improved outcomes when statins are prescribed after discharge
November 17, 2017 - Majority of people do not understand link between obesity and cancer, study shows
November 17, 2017 - Deep vein thrombosis accurately diagnosed by GPs trained in compression ultrasonography
November 17, 2017 - New Kevlar-based hydrogel recreates the magic of natural cartilage
November 17, 2017 - FDA approves first adjuvant treatment to reduce risk of kidney cancer recurrence
November 17, 2017 - Foods made with biofortified corn flour and eggs retain vitamin A after cooking
November 17, 2017 - Integrated Care Winning the Day for Healthcare Companies
November 17, 2017 - CPAP may be superior to gastric banding for severe sleep apnea
November 17, 2017 - New pain relievers reduce opiate overdose risk
November 17, 2017 - Brain astrocytes could play key role in pathogenesis of Alzheimer’s disease
November 17, 2017 - Researchers test whether LVAD surgery could reverse frailty in older adults with heart failure
Microbiologists contribute to possible new anti-TB treatment path

Microbiologists contribute to possible new anti-TB treatment path

image_pdfDownload PDFimage_print
The Morita lab at UMass Amherst is expert in investigating the multi-layered cell envelope components that surround mycobacteria. He sees the pathways that cells use to form these envelope layers as a promising path in the search for new drug targets in TB, which has seen increasing multi-drug resistance. Credit: UMass Amherst

As part of the long effort to improve treatment of tuberculosis (TB), microbiologists led by Yasu Morita at the University of Massachusetts Amherst report that they have for the first time characterized a protein involved in making a glycolipid compound found in the TB cell wall, which is critical for the disease-causing Mycobacterium to become infectious.

Doctoral candidate and first author Kathryn Rahlwes, working with a non-pathogenic form of the bacterium in Morita’s lab, says, “We found mutant bacteria that were unable to express this protein. If they don’t have it, the enzymatic machinery they use to biosynthesize the glycolipid won’t work, and they cannot become infectious. We investigated a protein that had not been characterized before, nobody knew its role.” Details appear in the Journal of Biological Chemistry.

The Morita lab is expert in investigating the multi-layered cell envelope components that surround mycobacteria, including several glycolipids known or predicted to be essential for the overall viability of disease-causing Mycobacterium tuberculosis (Mtb), which have impermeable cell walls that block antibiotics. Morita sees the biosynthesis pathways that cells use to form these envelope layers as a promising path in the search for new drug targets in TB, a disease that has seen increasing multi-drug resistance.

He explains, “The protein that Kathryn characterized is part of the process by which these molecules trick the human immune system so that it doesn’t attack the bacteria as hard as it should, so they survive in the body. TB has many, many tricks and this is one of them. Understanding how the bacteria make these glycolipids might provide us a way to interfere with them and stop them from being able to infect us.”

For this work, Rahlwes used genetic screening methods to explore the mutant of Mycobacterium that contains the protein known as PimE. It had been identified earlier in the Morita lab and was known to have some unusual properties.

Morita explains, “We were growing some of the mutant Mycobacterium in a Petri dish, and they grew very poorly; the mutant colonies had a growth disadvantage. Then we isolated a mutant of the mutant, and these suddenly began growing well again. It didn’t make sense, and we became curious about what was going on. Why did one defect make them grow slowly and poorly, but two defects made them run normally again?”

It turns out that the “mutant mutant” has an initial growth defect plus another mutation in the same glycolipid biosynthesis pathway and the second mutation allows these bacteria to enjoy more normal growth. “This led us to the discovery of a new gene in the biosynthesis of this glycolipid, which we termed lipomannan elongation factor or LmeA,” Rahlwes says. “The mutated gene caused the production of different glycolipids in the mutant of the mutant.”

Next steps include trying to duplicate the mutant of this gene in the pathogenic form of mycobacteria, to demonstrate that the gene is indeed essential as predicted for infection to take place, the microbiologists say.

Rahlwes also plans to further investigate the protein’s role in the enzymatic pathway and which parts it is interacting with. “We know it’s involved, but not exactly what it’s doing,” she says. “We’d like to confirm its function in the pathogen and its impact on the pathogen’s growth. If it is essential for the pathogen to grow, and if we are able to deplete it in the pathogen, we will be able to interfere in the infection process.”


Explore further:
Mutant gene found to fuel cancer-promoting effects of inflammation

More information:
Kathryn C. Rahlwes et al, The cell envelope–associated phospholipid-binding protein LmeA is required for mannan polymerization in mycobacteria, Journal of Biological Chemistry (2017). DOI: 10.1074/jbc.M117.804377

Journal reference:
Journal of Biological Chemistry

Provided by:
University of Massachusetts Amherst

Tagged with:

About author

Related Articles