May 17, 2017 Credit: MIPT Press Office
Researchers from the Vavilov Institute of General Genetics of the Russian Academy of Sciences (VIGG) and the Moscow Institute of Physics and Technology (MIPT) have established a catalog of mutations in 319 virulence genes of mycobacteria that cause tuberculosis. These genes encode proteins that suppress human immune response. Further analysis has identified a set of three mutations which may enable mycobacteria to develop rapidly in an immunocompromised environment. The emerging strains of TB pathogens require new treatment approaches, including the development of new genetically engineered vaccines that take into account both the immune status of a patient and the specific virulence features of a pathogen. The article was published in Genome Biology and Evolution.
Lost battle
According to the World Health Organization, TB remains one of the most dangerous human infectious diseases, causing over 1.8 million deaths annually. TB is caused by a bacterium known as Mycobacterium tuberculosis or Koch's bacillus. It is clear that HIV-positive individuals and patients with other immunodeficiency conditions are particularly at risk. Additionally, more than 20 percent of TB cases are connected with smoking. TB is no longer a social disease, affecting members of all social strata, a result of the stresses of modern life.
M. tuberculosis has become increasingly resistant to both the environmental factors and antibiotics that used to guarantee effective treatment. At the same time, the symptoms of TB have become less noticeable. The bacterium can remain in the host body for decades, infecting other people. According to WHO statistics, one-third of the world's population is infected with TB. The most serious problem is drug-resistant TB aggravated by the adaptation of new pathogenic strains to weakened immunity.
Prof. Valery Danilenko, the head of the Department of Genetics and Biotechnology at VIGG, comments on the issue: "Humanity is trying to beat the disease with new drugs and innovative treatment methods, but we havetactically speakingalready lost the battle. During the last 50 years of research, only one antibiotic with a novel type of action has been producedBedaquiline. It has been in use for about two years, now. However, mycobacteria have already developed mutations that make them resistant to that drug."
New strains of drug-resistant bacteria with altered virulence have already emerged, exploiting precisely this weakness by targeting immunodeficient patients.
Bioinformatics and genetics help identify a dangerous strain of TB pathogens
Researchers currently identify seven to eight major M. tuberculosis lineages (groups). They differ from one another in mutations of various genes. A genome can have from 300 to 1,000 of such lineage-specific mutations, or SNPs. The term SNP (pronounced "snip") means a mutation in a particular gene involving the substitution of only one nucleotide. If the mutation occurs in a functional part of a virulence gene, the protein encoded by that gene will trigger a different host immune response. This enables the pathogen to overcome host resistance mechanisms developed in childhood as a result of BCG (anti-TB) vaccination.
Natalya Mikheecheva, a researcher at the Laboratory of Bacterial Genetics at VIGG with a bioinformatics degree from MIPT, explains, "We carried out research aimed at identifying the genes and mutations that allow mycobacteria to thrive in people with altered immune status, including HIV-positive patients. We developed a catalog of SNPs in more than 300 virulence genes. Virulence was defined as the ability of a pathogen to cause disease, overcome host resistance via invasion and adhesion to host cells, and adapt to hostile environments, including immune response modulation."
Each lineage was found to comprise dozens or even hundreds of sublineages, depending on the specific gene and the location of the mutation. Bioinformatics analysis conducted using software developed at MIPT's Department of Biological and Medical Physics (MIPT) revealed mutations specific to an epidemiologically dangerous sublineage within the Beijing-B0 lineage.
The scientists used databases of sequenced and described genomes to track the spread of the epidemiologically dangerous B0/N-90 sublineage in Russia and the neighboring European countries Belarus, Moldova and Sweden.
Development of new vaccines
To combat drug-resistant TB, an international consortium called TBResist formed in 2008. Its members include leading experts in medicine, genetics, bioinformatics, etc. from the U.S., Sweden, Russia, the U.K., Bangladesh, Zimbabwe, South Africa, Taiwan, and other countries.
Prof. Danilenko, who led the research in Russia, says, "Our work with the international consortium involved cooperating with our colleagues from South Africa and China to draft a project aimed at investigating the epidemiologically dangerous strain identified in our study. The project is currently being considered by expert communities of the three countries, including the Ministry of Education and Science of the Russian Federation. Our goal is to warn the international community and the health ministries of the BRICS countries of the impending danger. In the '80s, it was HIV. We may well expect something similar from new mutated TB strainsit's a Pandora's box."
Treatments that are available now can cure the disease within a year or two. However, we could see the emergence of mutant pathogens developing rapidly in certain population groups. With the flu, there is an established practice of making a new vaccine every year to counteract the latest mutated strain of influenza. But unlike the influenza virus, which only has several genes, M. tuberculosis has more than 300 virulence genes, each of them potentially subject to mutations.
For the last 30 years, scientists all over the world have been trying to design a genetically engineered TB vaccine. To do this, only certain genes of the bacterium are used, not its whole genome. These genes are cloned to obtain their protein products, which are then used to vaccinate patients and monitor their immune response. There are, however, hundreds of M. tuberculosis sublineages. The research findings indicate that vaccines need to take into account such factors as the host's immune status and the presence in the pathogen of any of at least a dozen epidemiologically dangerous lineages with mutations in particular virulence genes.
Prof. Danilenko drives the point home: "We detected mutations that may enable the bacteria to thrive by exploiting compromised immunity. From that point, it is basically analogous to the flu. We suggest that vaccines against specific TB lineages need to be developed using the genes identified through the bioinformatics analysis of hundreds of sequenced genomes. This will help us to find a basic approach that could inhibit the spread of the dangerous lineages. We have also developed diagnostic tests to identify such lineages."
Explore further: 'Survival gene' stops strains of tuberculosis mutating into deadly 'superbugs'
More information: Natalya E. Mikheecheva et al, A Nonsynonymous SNP Catalog of Mycobacterium tuberculosis Virulence Genes and Its Use for Detecting New Potentially Virulent Sublineages, Genome Biology and Evolution (2017). DOI: 10.1093/gbe/evx053
Scientists have discovered a key 'survival gene' that prevents strains of tuberculosis (TB) from mutating into drug-resistant 'superbugs'.
Salmonella infections are typically the culprit behind food poisoning outbreaks, but in sub-Saharan Africa, they often cause drug-resistant, deadly bloodstream infections and meningitis. A study in mice published February ...
Proteins produced by the parasite that causes toxoplasmosis may be involved in immune system processes that can help fight mycobacteria, according to a new study. The findings, published in PLOS Pathogens, suggest that these ...
A new generation of drugs could help combat the growing number of bacterial diseases that are becoming resistant to antibiotics, a study reveals.
(HealthDay)Getting hospital patients with mild pancreatitis to start eating sooner may speed their recovery, a new study says.
A team of investigators led by Rohit Kohli, MBBS, MS, of Children's Hospital Los Angeles, has identified key inflammatory cells involved in nonalcoholic fatty liver disease. Current treatment for the disorder involves changes ...
An international study led by Monash University has discovered the molecular mechanism by which the potentially deadly superbug 'Golden Staph' evades antibiotic treatment, providing the first important clues on how to counter ...
Vaccinating pregnant mothers year-round against flu in the resource-challenged region of subtropical Nepal reduced infant flu virus infection rates by an average of 30 percent, increased birth weights by 15 percent and resulted ...
Researchers from the University of Liverpool have conducted a study of Ebola survivors to determine if the virus has any specific effects on the back on the eye using an ultra widefield retinal camera.
Ebola outbreaks are set to be managed quickly and efficiently - saving lives - with a new approach developed by an international team of researchers, including the University of Warwick, which helps to streamline outbreak ...
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more
View post:
TB bacteria evolve at alarming rate - Medical Xpress
- MOgene Announces Partnership with Intuitive Genomics to Expand Bioinformatics Capabilities - January 28th, 2013 [January 28th, 2013]
- Bioinformatics Organization - Bioinformatics.Org Wiki - January 17th, 2014 [January 17th, 2014]
- Bioinformatics Market by Application (Genomics, Molecular Phylogenetics, Metabolomics, Proteomics, Chemoinformatics ... - April 9th, 2014 [April 9th, 2014]
- Bioinformatics Master of Science - Northeastern ... - April 9th, 2014 [April 9th, 2014]
- Master of Science in Bioinformatics | AAP | JHU - April 9th, 2014 [April 9th, 2014]
- Bioinformatics - Bioinformatics.Org Wiki - April 9th, 2014 [April 9th, 2014]
- Bioinformatics Organization - Bioinformatics.Org - April 9th, 2014 [April 9th, 2014]
- Bioinformatics - Wikipedia, the free encyclopedia - April 9th, 2014 [April 9th, 2014]
- Identified epigenetic factors associated with increased risk of developing cancer - April 10th, 2014 [April 10th, 2014]
- Home | Department of Computational Medicine & Bioinformatics - April 10th, 2014 [April 10th, 2014]
- Bioinformatics tool - Video - April 10th, 2014 [April 10th, 2014]
- individual assignment CADD-Bioinformatics tools - Video - April 10th, 2014 [April 10th, 2014]
- MARC travel awards announced for the 2014 Great Lakes Bioinformatics Conference - April 15th, 2014 [April 15th, 2014]
- PH genome center unveils facility powered by IBM supercomputer - April 15th, 2014 [April 15th, 2014]
- Part 1 : Introduction to Bioinformatics, PDB and EMBL-EBI - Video - April 15th, 2014 [April 15th, 2014]
- Bioinformatics - Video - April 15th, 2014 [April 15th, 2014]
- March's Bioinformatics Papers of Note - April 18th, 2014 [April 18th, 2014]
- BMC Bioinformatics - BioMed Central | The Open Access ... - April 22nd, 2014 [April 22nd, 2014]
- Bioinformaticsweb.co.nr:Open Access Bioinformatics ... - April 22nd, 2014 [April 22nd, 2014]
- Penn Bioinformatics Profiling Identifies a New Mammalian Clock Gene - April 22nd, 2014 [April 22nd, 2014]
- Bioinformatics profiling identifies a new mammalian clock gene - April 22nd, 2014 [April 22nd, 2014]
- UST Bioinformatics 2014 Project YOUTUBE - Video - April 22nd, 2014 [April 22nd, 2014]
- First Sex Determining Genes Appeared In Mammals Some 180 Million Years Ago - April 25th, 2014 [April 25th, 2014]
- Pronounce Medical Words Bioinformatics - Video - April 25th, 2014 [April 25th, 2014]
- Funding Update: NIH Bioinformatics Grants Awarded March 13, April 24, 2014 - April 25th, 2014 [April 25th, 2014]
- BIOINFORMATICS - blogspot.com - April 25th, 2014 [April 25th, 2014]
- Biology, Computers Collide in High-Demand Field of Bioinformatics - Video - April 25th, 2014 [April 25th, 2014]
- Researchers Discover Effect Of Circulating Cell Types On Cardiovascular Health - April 30th, 2014 [April 30th, 2014]
- The Genomics and Bioinformatics Group - April 30th, 2014 [April 30th, 2014]
- BIT001 Bioinformatics assignments 5 and 6 - Video - April 30th, 2014 [April 30th, 2014]
- Visual Genome Analysis Suite Bioinformatics Software Demonstration - Video - May 1st, 2014 [May 1st, 2014]
- Bioinformatics Erasing the line between biology and hacking Krystal Thomas White and Patrick Thomas - Video - May 1st, 2014 [May 1st, 2014]
- Cambridge genomics duo in the steps of Pasteur - May 2nd, 2014 [May 2nd, 2014]
- bioinformatics-phamerator - Video - May 3rd, 2014 [May 3rd, 2014]
- Metal Slug 3 Soundtrack - Bioinformatics Extendido - Video - May 3rd, 2014 [May 3rd, 2014]
- Bioinformatics approach helps researchers find new uses for old drug - May 5th, 2014 [May 5th, 2014]
- Bioinformatics Approach Helps Researchers Find New Use for Old Drug - May 5th, 2014 [May 5th, 2014]
- Biotech industry to touch $7-bn mark by FY15: Study - May 6th, 2014 [May 6th, 2014]
- Biotech industry to touch $7 bn mark by FY15-end: study - May 6th, 2014 [May 6th, 2014]
- How immune cells use steroids - May 9th, 2014 [May 9th, 2014]
- IP Update: New York University, Microsoft among Recent Bioinformatics Patent Winners - May 10th, 2014 [May 10th, 2014]
- Introduction to Bioinformatics Presenter - Video - May 10th, 2014 [May 10th, 2014]
- Dr. Jessica Schlueter Discusses Bioinformatics Research - Video - May 11th, 2014 [May 11th, 2014]
- Bioinformatics Software Carpentry Bootcamp - Session 4 - Video - May 11th, 2014 [May 11th, 2014]
- SBRI backs Eagles genomic data technology - May 12th, 2014 [May 12th, 2014]
- Bioinformatics firm SolveBio Seeks to Build Business on Providing Painless Access to Curated Data - May 16th, 2014 [May 16th, 2014]
- Szilak Lab Bioinformatics and Molecule Design, HUNGARY (MIT-LS 2014) - Video - May 16th, 2014 [May 16th, 2014]
- Happy birthday Prof Usman from bioinformatics team - Video - May 16th, 2014 [May 16th, 2014]
- KARUNYA BIOINFORMATICS - Video - May 18th, 2014 [May 18th, 2014]
- Global Market for Biomarkers to Reach $53.6 Billion in 2018; Bioinformatics to Move at 17.4% CAGR - May 20th, 2014 [May 20th, 2014]
- Careers in Bioinformatics and Precision Medicine - Career Development Week - Video - May 21st, 2014 [May 21st, 2014]
- Big Data Lets Cancer Researchers Put Old Drugs to New Uses - May 22nd, 2014 [May 22nd, 2014]
- Fugeneio The Fest - Fugeitorium - Bioinformatics Experience in 3D - Video - May 22nd, 2014 [May 22nd, 2014]
- The Hyve - OpenSource Bioinformatics - Video - May 24th, 2014 [May 24th, 2014]
- DNA sequences on the go, with an app born in a Singapore lab - May 29th, 2014 [May 29th, 2014]
- :: 29, May 2014 :: POCKET SCIENCE: NEW MOBILE APPLICATION ENABLES DNA ANALYSIS ON THE GO - May 29th, 2014 [May 29th, 2014]
- Bioinformatics Market is Expected to Grow at a CAGR of over 23.0% from 2014 to 2020 New Report Published By Grand View ... - May 29th, 2014 [May 29th, 2014]
- Professor Bud Mishra, PhD Joins the Science Advisory Board of InSilico Medicine Engaged in Aging Research for Drug ... - May 30th, 2014 [May 30th, 2014]
- A holistic view on bioinformatics market - Video - June 1st, 2014 [June 1st, 2014]
- Viral Safety Testing using an advanced next generation sequencing and bioinformatics platform - Video - June 1st, 2014 [June 1st, 2014]
- Balti and Bioinformatics - Tom Connor - CLIMB - Video - June 2nd, 2014 [June 2nd, 2014]
- Global Bioinformatics Market All Set to Register a CAGR of 21.2% According to The Newly Added Report at Analyze Future - June 4th, 2014 [June 4th, 2014]
- Bioinformatics basic database and tools - Video - June 4th, 2014 [June 4th, 2014]
- Bioinformatics Market Reports by Analyze Future - Video - June 4th, 2014 [June 4th, 2014]
- Bioinformatics | Johns Hopkins University Engineering for ... - June 6th, 2014 [June 6th, 2014]
- Global Bioinformatics Market Report by Truemarketresearch - Video - June 7th, 2014 [June 7th, 2014]
- A Web-Based System for Automatic Bioinformatics Data Classification - Video - June 12th, 2014 [June 12th, 2014]
- Bioinformatics Welcome Video - Video - June 12th, 2014 [June 12th, 2014]
- Bioinformatics Services: Surfing the Data Wave - Video - June 12th, 2014 [June 12th, 2014]
- 4th International Conference on Proteomics & Bioinformatics - Video - June 12th, 2014 [June 12th, 2014]
- Institute of Bioinformatics featured on Rajyasabha TV - Video - June 14th, 2014 [June 14th, 2014]
- Global Bioinformatics Market - Analysis, Opportunities, Segmentation and Forecast, 2013 - 2020 - Video - June 21st, 2014 [June 21st, 2014]
- 6/18/14 Bioinformatics: Computer Technology & Biological Info on Across The Fence - Video - June 21st, 2014 [June 21st, 2014]
- JAX, Frasergen announce cancer genomics facility in Hubei Province, China - June 22nd, 2014 [June 22nd, 2014]
- UK-Colombia alliance on global food security - June 22nd, 2014 [June 22nd, 2014]
- Global Bioinformatics Market Size, Trends, Analysis, Report, Growth, Forecast 2013 - 2020 - Video - June 23rd, 2014 [June 23rd, 2014]
- Aging Accelerates Genomic Changes, Signaling Challenges for Personalized Medicine - June 24th, 2014 [June 24th, 2014]
- Researchers treat incarceration as a disease epidemic, discover small changes help - June 26th, 2014 [June 26th, 2014]
- Atul Butte, MD, discusses bioinformatics in pediatric health, Packard Children's Hospital - Video - June 27th, 2014 [June 27th, 2014]
- Metal Slug 3 OST#23 Bioinformatics - Video - June 27th, 2014 [June 27th, 2014]