Breaking News
November 12, 2018 - Cocaine Cut With Anti-Worming Drug, Levamisole, May Cause Brain Damage
November 12, 2018 - Obese mice lose a third of their fat using a natural protein
November 12, 2018 - Behind many a Parkinson’s case lurks a mutation in a gene called LRRK2 — why?
November 12, 2018 - Drug with fish oil cuts risk of heart attack, stroke, study finds
November 12, 2018 - Mild exposure to single blast can induce meaningful pathogenic effects, study shows
November 12, 2018 - Miniature pacemakers aim to make heart procedures for infants less invasive, more efficient
November 12, 2018 - Treating pre-cancerous stem cells at early stage could be key to preventing bowel cancer
November 12, 2018 - Kawasaki disease triggered by a combination of factors
November 12, 2018 - Optibrium and University of Nottingham Collaborate on Innovative Teaching Programme
November 12, 2018 - RNA defects linked to multiple myeloma progression in high risk patients
November 12, 2018 - Science is on trial – and we need doctors to provide the defense
November 12, 2018 - Salk researchers receive $19.2 million to unravel mysteries of age-related cognitive decline
November 12, 2018 - KE Eye Centers offer new solution for patients with myopia and astigmatism
November 12, 2018 - Trumpeted new Medicare Advantage benefits will be hard for seniors to find
November 12, 2018 - Biogen and Eisai Announce Presentation of Detailed Analyses from the Phase 1b Long-Term Extension Study of Aducanumab at Clinical Trials on Alzheimer’s Disease (CTAD)
November 12, 2018 - Scientists reveal new cystic fibrosis treatments work best in inflamed airways
November 12, 2018 - Inexpensive and effective drug does not reduce major adverse cardiovascular event rates
November 12, 2018 - Testing coronary calcium levels can better predict patient’s risk for coronary heart disease
November 12, 2018 - FDA conducts mass seizure of food and medical products held under insanitary conditions
November 12, 2018 - FDA Approves Invokana (canagliflozin) to Reduce the Risk of Heart Attack, Stroke or Cardiovascular Death in Adults with Type 2 Diabetes and Established Cardiovascular Disease
November 12, 2018 - Hormone helps reverse brain damage caused by obesity
November 12, 2018 - Grants aim to provide better cancer clinical trial access for military veterans
November 12, 2018 - Mitochondrial DNA may have strong influence on cellular metabolism and disease susceptibility
November 12, 2018 - High stakes, entrenched interests and the Trump rollback of environmental regs
November 12, 2018 - Stem cells transplanted for treatment of Parkinson’s disease
November 12, 2018 - Sandoz Inc. Issues Voluntary Nationwide Recall of One Lot of Losartan Potassium and Hydrochlorothiazide Due to the Detection of Trace Amounts of NDEA (N-Nitrosodiethylamine) Impurity Found in the Active Pharmaceutical Ingredient (API)
November 12, 2018 - Protein found in patients with severe asthma can help identify who would benefit from targeted drugs
November 12, 2018 - Experts develop a list of competencies in antimicrobial prescribing and stewardship
November 12, 2018 - Allied BioScience receives approved label from EPA for new bacteriostatic surface coating
November 12, 2018 - MR Solutions displays elegant bench top CT scanner with clip-on PET and SPECT at EANM congress
November 12, 2018 - FDA announces emergency use authorization of Ebola fingerstick test with portable reader
November 12, 2018 - Grieving spouses with sleep problems have increased risk of chronic immune activation
November 12, 2018 - Exercise routines affect mental health in Japanese expatriates
November 12, 2018 - Fish oil and vitamin D pills no guard against cancer or serious heart trouble
November 12, 2018 - Excess Gestational Weight Gain Not Better for Child Bone Health
November 12, 2018 - Immune receptor provides protective immunity against Group A Streptococcus
November 12, 2018 - Scientists develop new method to produce irradiated nanomaterials for medical applications
November 12, 2018 - Blue light exposure decreases blood pressure
November 12, 2018 - Researchers discover two proteins essential for development of skeletal muscle
November 12, 2018 - Yelp reviews help understand strengths, weaknesses of emergency departments and urgent care centers
November 12, 2018 - Adolescent obesity linked with increased risk of pancreatic cancer later in life
November 12, 2018 - AHA: Poor Teeth-Brushing Habits Tied to Higher Heart Risk
November 12, 2018 - Researchers find how natural killer cells regulate protective HIV antibodies
November 12, 2018 - Rutgers receives $4.2 million federal grant to improve mental health services
November 12, 2018 - Sussex scientists develop a piece of hardware to show how brains function
November 12, 2018 - Study shows pivotal role of parents in efforts to change sexual orientation of LGBT teens
November 12, 2018 - Neck scan detects dementia way before symptoms appear
November 12, 2018 - Risk-profiling can benefit HIV prevention
November 12, 2018 - New thrombolytic based on magnetite nanoparticles successfully tested on animals
November 12, 2018 - Smoking rates go down in the US, lowest since 1965
November 12, 2018 - Phase III Trial of Darolutamide in Patients with Non-metastatic Castration-resistant Prostate Cancer Meets Primary Endpoint
November 12, 2018 - Moderate exercise before conception resulted in lower body weight, increased insulin sensitivity of offspring
November 11, 2018 - Community choirs for older adults reduce loneliness and increase interest in life
November 11, 2018 - Trevena Receives Complete Response Letter for Oliceridine from FDA
November 11, 2018 - More adults and children are using yoga and meditation
November 11, 2018 - Female smokers at greater risk of heart attacks, finds study
November 11, 2018 - Happy Childhood Memories Associated With Better Health
November 11, 2018 - X-linked infantile spinal muscular atrophy – Genetics Home Reference
November 11, 2018 - RNA thought to spread cancer shows ability to suppress breast cancer metastasis
November 11, 2018 - Study finds that thymus plays key role during normal pregnancy
November 11, 2018 - Exploring why some athletes ice their muscles after exercise
November 11, 2018 - Female Genital Mutilation Decreasing in African Nations
November 11, 2018 - Are humans immune to the CRISPR-Cas9 gene editing scissors?
November 11, 2018 - Breastmilk and saliva mixtures regulate oral microbiome of newborn babies
November 11, 2018 - Learning familiar faces through social interactions reduces variability in face recognition
November 11, 2018 - New open source decision support tool could help clinicians chose chemotherapy drugs
November 11, 2018 - New weapons drawn in global TB fight
November 11, 2018 - UCB and Biogen Announce Topline Results from a Phase 2b Study of Dapirolizumab Pegol in Systemic Lupus Erythematosus
November 11, 2018 - Surgery restores boy’s ability to walk post-acute flaccid myelitis
November 11, 2018 - Comorbidity negatively impacts quality of life in people with dementia
November 11, 2018 - Neuroscientists receive $16.75 million from BRAIN Initiative to decipher the brain’s visual system
November 11, 2018 - Purdue researchers invent new smart drainage device to help glaucoma patients
November 11, 2018 - New initiative may benefit entrepreneurs working to transform patient care
November 11, 2018 - Sage Therapeutics Announces FDA Advisory Committee Votes 17-1 in Support of Benefit-Risk Profile of Zulresso (brexanolone) Injection for Treatment of Postpartum Depression
November 11, 2018 - Exercise could delay progression of type 1 diabetes when first diagnosed
November 11, 2018 - Study of gaze fixation in monkeys reveals role of dopamine neurons in response inhibition
November 11, 2018 - Bilingual therapy is vital to improve language disorders in dual-language children, finds study
November 11, 2018 - More Frequent Surveillance No Benefit After NSCLC Resection
November 11, 2018 - Phenylketonuria (PKU) Screening: MedlinePlus Lab Test Information
November 11, 2018 - Researchers discovered a new mechanism of action in a first-line drug for diabetes
Researchers move closer to finding potential soft spot in drug-resistant tuberculosis

Researchers move closer to finding potential soft spot in drug-resistant tuberculosis

image_pdfDownload PDFimage_print

Antibiotic-resistant tuberculosis is a public health threat. TB and other bacteria become resistant to antibiotics by evolving genetic changes over time, which they can do quite quickly because bacterial lifecycles are short. In fact, it takes only a single genetic mutation to grant TB resistance to isoniazid, one of the first-line antibiotics.

Intrigued that such a small change results in such a consequential outcome, researchers led by Karen Dobos at Colorado State University undertook a study to determine what other effects might result from that same gene tweak. If they could uncover changes that make antibiotic-resistant TB vulnerable in other ways, Dobos’ team reasoned, they or others might be able to one day target those weaknesses.

The team’s results, including new information about a potential TB soft spot, recently were published in the journal Molecular & Cellular Proteomics.

In order to understand why Dobos’ team did what it did, you have to keep in mind that TB, as the infection progresses, is constantly evolving. An antibiotic that beats back TB at first can lose its effectiveness.

You also have to know that the antibiotic isoniazid depends on a protein produced by TB to extinguish TB. That is, the genetic change that makes TB resistant to isoniazid actually hinders production of that key TB protein. If the protein, called KatG, isn’t there or is there but is in poor shape, the infection can rage on unencumbered by the antibiotic.

First, Dobos and her colleagues obtained a TB strain sample from a patient at two different times: before beginning isoniazid and after the antibiotic stopped working. With those two samples in hand, the researchers examined proteomic and metabolic differences in the strains. They wanted to find out how losing KatG, which the second sample had done, affected other aspects of the bacterial cell.

The researchers also examined TB strains, both responsive and resistant to the antibiotic, that had developed in another lab in a mouse model. “Our expectation was that the lab-generated mutant and the clinical mutant would be relatively the same,” said Dobos. “Whole-genome sequencing didn’t show us anything substantially different.”

But while the bacteria from both the patient and the mouse had similar changes in KatG and no changes in other genes known to relate to virulence or drug resistance, the virulence of the strains turned out to be profoundly different. The resistant patient strain was much less deadly than its parent strain, but the resistant mouse strain wasn’t that different from its parent in terms of virulence.

Dobos calls this finding “a bit negative,” because it means the same genetic change won’t affect the bacteria in the same way every time.

Even so, the bacteria did share some changes that add to researchers’ body of knowledge about tuberculosis. For example, both strains that gained isoniazid resistance switched from reliance on glucose to reliance on fatty acids for energy. The fatty-acid metabolism pathway is already under investigation as a drug target by other groups.

That pathway is a strong candidate for targeting in patients with isoniazid-resistant infections, Dobos explained, “because it is unique to bacteria and it’s additionally unique to mycobacteria.” In other words, humans lack the pathway, so targeting it won’t disable it in patients, reducing the likelihood of side effects.

Dobos said she hopes that a drug targeting that TB pathway “would be well tolerated and reduce some of the terrible problems that people who need multidrug therapy face.”

Tagged with:

About author

Related Articles