Predicting nitroimidazole antibiotic resistance mutations. Mar 24, 2020 mycobacterium tuberculosis and rifampin resistance, united kingdom. Antibioticresistant tuberculosis poses a significant and growing threat to global health. Some forms of tb are also resistant to secondline medications, and are called extensively drugresistant tb. Methods a comprehensive systematic search of pubmed, web of science and sciencedirect for. A comprehensive understanding of the preexisting genetic variation in genes associated with antibiotic resistance in the mycobacterium tuberculosis complex mtbc is needed to accurately interpret wholegenome sequencing data for genotypic drug susceptibility testing dst. The emergence of drug resistant tb is most often attributed to poor. Staphylococcus epidermidis bacteria, niaid from flickr. Tb usually affects the lungs, but it can also affect other parts of the body, such as the brain, the kidneys, or the spine. Evolution of drug resistance in mycobacterium tuberculosis. One clear exception is mycobacterium tuberculosis mtb. Tuberculosis tb is a serious public health problem worldwide. Antibiotic resistance is one of the biggest threats to human health globally.
A better knowledge of the mechanisms of drug resistance of m. Mycobacterium tuberculosis mtb causes the disease tuberculosis tb, which kills more people than any other infection. When several cultures were positive for the same patient, only one was tested to detect drug resistances. This work was partially supported by instituto mexicano del seguro social fis imssprotg151457. The problem of tuberculosis is hampered by the emergence of multi drug resistant mdr and extensively drug. Tuberculosis tb is a disease caused by bacteria that are spread from person to person through the air. The effect of mutational events that lead to antibioticresistant phenotypes may or may not have a predictable effect on the. Antibiotic resistance in mycobacterium tuberculosis sebastien gagneux,1,4 clara davis long,2 peter m. Multidrugresistant strains of mycobacterium tuberculosis seriously threaten tuberculosis tb control and prevention efforts. This coating makes the cells impervious to gram staining, and as a result, m.
Ancestral antibiotic resistance in mycobacterium tuberculosis rowan p. The effect of drug resistance on the fitness of mycobacterium. We show that in laboratoryderived mutants of mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. While wholegenome sequencing wgs, with its unprecedented level of detail, promises to play an increasingly important role in diagnosis, data analysis is a daunting challenge. Resistance to tuberculosis tb drugs is a formidable obstacle to effective tb care and prevention globally.
Discordant resistance to kanamycin and amikacin in drugresistant mycobacterium tuberculosis antimicrobial agents and chemotherapy, 2004, 47, 29712973 ii. Molecular studies of the mechanism of action of antitubercular drugs have elucidated the genetic basis of drug resistance in m. Integrating standardized whole genome sequence analysis with. Thompson departments of medicine and of microbiology and immunology, division of infectious diseases and geographic. However, tb remains a global public health threat and recently. Multidrugresistant tuberculosis mdrtb is a form of tuberculosis tb infection caused by bacteria that are resistant to treatment with at least two of the most powerful firstline antitb medications drugs, isoniazid and rifampin.
Even though the high level of resistance to ofloxacin found in pakistan is worrisome because it might be the expression of extensive and unregulated use of fluoroquinolones in some parts of asia, the. Jul 02, 2014 tuberculosis tb is a serious public health problem worldwide. Importance mycobacterium tuberculosis, the causative agent of tuberculosis tb, is a signi. Evaluation of the line probe assay lipa for rapid detection of rifampicin resistance in mycobacterium tuberculosis tuberculosis, 2004, 84, 3116 iii. Antibiotic treatment imposes strong selective pressure on m. Integrating standardized whole genome sequence analysis. Molecular characterisation of antibiotic resistance in. Mycobacterium tuberculosis remains a leading infectious cause of morbidity and mortality. The infection is usually treatable, and isoniazid isonicotinic acid hydrazide inh 4 has been a first line antibiotic against mycobacterium tuberculosis since 1952. Populationbased resistance of mycobacterium tuberculosis. Author summary bacterial pathogens often evolve resistance to antibiotics via mutations in the coding sequences of genesfrequently the target, an enzyme that metabolizes or transports the active drug, or an enzyme that activates a prodrug.
Phylogenetically informative mutations in genes implicated. Jun 30, 2006 mathematical models predict that the future of the multidrugresistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We have identified a small molecule, c10, that potentiates the activity of the frontline antibiotic isoniazid inh and prevents the selection for inhresistant mutants. Bohannan2 mathematical models predict that the future of the multidrugresistant tuberculosis epidemic will. Antibioticresistant mycobacterium tuberculosis strains are threatening progress in containing the global tuberculosis epidemic. Ancestral antibiotic resistance in mycobacterium tuberculosis. Contributing factors to the emergence of drug resistance in mycobacterium tuberculosis. Ancestral antibiotic resistance in mycobacterium tuberculosis article pdf available in proceedings of the national academy of sciences 10234. In the last decades, evolutionary studies have much improved our knowledge on mtbc history and have highlighted its long coevolution with humans. Mycobacterium tuberculosis and rifampin resistance, united kingdom. Medical xpress a team of researchers from sweden, france, belgium and switzerland has found a way to reverse resistance to an antibiotic drug used to treat tuberculosis. Oct 18, 2018 tuberculosis tb, caused by mycobacterium tuberculosis complex mtbc, was declared a global public health emergency in 1993 1. Mycobacterium tuberculosis is intrinsically resistant to many antibiotics, limiting the number of compounds available for treatment. Current treatment regimens for mycobacterium tuberculosis mtb, the causative agent of tuberculosis, are long, complex, and hard for people to sustain.
Tuberculosis tb remains one of the leading causes of death worldwide. Drug resistance mechanisms in mycobacterium tuberculosis. This intrinsic resistance is due to a number of mechanisms including a thick, waxy. The emergence of drugresistant mtb strains has exacerbated this already alarming epidemic.
Phylogenetically informative mutations in genes implicated in. Chemical disarming of isoniazid resistance in mycobacterium. Mycobacterium tuberculosis bacteria, niaid from flickr. Targeting antibiotic resistance mechanisms in mycobacterium tuberculosis recharging the old magic bullets. While antibiotic resistance is cited as a potential threat to efforts aimed at controlling the spread of this pathogen, it is not clear how drug resistance affects disease dynamics. Tb is caused by mycobacterium tuberculosis, bacteria that usually attack the lungs. Effective treatment and control of tb are complicated by the emergence and spread of drugresistant, multidrugresistant mdr, or even extensively drugresistant xdr strains. Mycobacterial mutagenesis and drug resistance are controlled. Mdr mycobacterium tuberculosis complex mtbc strains. Review on molecular mechanism of first line antibiotic resistance in. A large scale evaluation of tbprofiler and mykrobe for. Background tuberculosis tb remains a main global public health problem. Mutagenic dna repair is the ultimate cause of antibiotic resistance in mycobacterium tuberculosis, yet the mechanisms that control the genesis of these mutations are incompletely understood. Reversion of antibiotic resistance in mycobacterium.
Resistance of mycobacterium tuberculosis to antibiotics in. Its situation is worsened by the presence of multidrug resistant mdr strains of mycobacterium tuberculosis, the causative agent of the disease. Five of them were isolated from new cases and were resistant to inh. We investigated mutations in 92 genes implicated in resistance to 21 antituberculosis drugs using the genomes of 405 phylogenetically diverse mtbc strains. Rapid antibioticresistance predictions from genome sequence. We investigated mutations in 92 genes implicated in resistance to 21 antituberculosis drugs using the genomes of 405. Resistance of mycobacterium tuberculosis to antitb drugs is man made. New approach may help kill mycobacterium tuberculosis. Exposure to drugs induces a complex stress response in m. Drug resistance in mycobacterium tuberculosis intechopen.
The complex evolution of antibiotic resistance in mycobacterium. In the last decades, evolutionary studies have much improved our knowledge on mtbc history and have highlighted its long coevolution. In 20, an estimated 9 million people developed tb and 1. It has existed in humans since ancient times and had high mortality rates without adequate treatment options before the invention of antibiotics, specifically streptomycin in 1943, that were potent enough to kill the bacteria. Jun 19, 20 cultures were examined once a week for 80 days.
Identifying the mutations that cause drug resistance in m. Tuberculosis tb, caused by mycobacterium tuberculosis complex mtbc, was declared a global public health emergency in 1993 1. An estimated 9 million people developed tuberculosis tb worldwide in 20. Predicting nitroimidazole antibiotic resistance mutations in. Antibiotic resistant tuberculosis poses a global threat, causing the deaths of hundreds of thousands of people annually. Antimicrobial resistance in mycobacterium tuberculosis. Dec 21, 2015 rapid antibiotic resistance predictions from genome sequence data for staphylococcus aureus and mycobacterium tuberculosis. Keywords mycobacterium tuberculosis, antibiotic resistance, machine learning introduction with more than a million deaths and 10 million new cases worldwide in 2017 world health organization, 2018a, tuberculosis, the disease caused by mycobacterium tuberculosis, is a major public health concern.
Pdf drug resistance in mycobacterium tuberculosis researchgate. Approximately five percent of tuberculosis strains worldwide are considered multidrugresistant, indicating that the bacteria have evolved resistance to two frontline antibiotics. Mycobacterium tuberculosis tb is an insidious scourge that has afflicted humans for thousands of years, and still remains one of the leading causes of death in the world, now estimated at 1. We investigated mutations in 92 genes implicated in resistance to 21 anti tuberculosis drugs using the genomes of 405. Mathematical models predict that the future of the multidrugresistant tuberculosis epidemic will depend on the fitness cost of drug resistance. Although pyrazinamide resistance was significantly associated with rifampicin resistance, this drug may still be effective in 1963% of patients with rifampicinresistant tuberculosis.
Tuberculosis infection kills nearly 2 million people a year and is the leading cause of death due to infectious diseases in adults and in aids patients. This intrinsic resistance is due to a number of mechanisms including a thick, waxy, hydrophobic cell envelope and. In recent years, even more serious forms of drug resistance have been reported. Antibiotic resistance in mycobacterium tuberculosis. The evolutionary trajectory of drugresistant mycobacterium tuberculosis. Antibiotic resistance mutations represent a selective advantage during antibiotic treatment, but in vitro studies have shown that they can significantly impair bacterial fitness in the absence of antibiotics. Rapid antibioticresistance predictions from genome. Some key antituberculosis antibiotics are prodrugs, for which resistance mechanisms are mainly driven by mutations in the bacterial enzymatic. Alarmingly, multidrugresistant and extensively drugresistant mycobacterium tuberculosis have now spread worldwide. The odd one out vegard eldholm1, and francois balloux2, antimicrobial resistance amr threats are typically represented by bacteria capable of extensive horizontal gene transfer hgt. Multidrugresistant tb mdrtb is multifactorial and fuelled by improper treatment of patients, poor management of supply and quality of drugs, and airborne transmission of bacteria in public places. Tuberculosis tb is among the most common infectious diseases and frequent causes of death worldwide claiming many of lives annually.
Bacteria, antibiotics and antibiotic resistance photo. Reports the competitive cost of antibiotic resistance in. Researchers find a way to reverse antibiotic resistance in. Antibiotic resistant mycobacterium tuberculosis strains are threatening progress in containing the global tuberculosis epidemic. Pdf treatment of tuberculosis tb has been a therapeutic challenge because of not only the naturally high resistance level of mycobacterium.
The management of the disease is complicated by the fact that bacterial. Although several gene mutations in specific loci of the m. Tuberculosis tb is a potentially deadly disease caused by pathogenic bacteria, usually mycobacterium tuberculosis. Pdf antibiotic resistance of mycobacterium tuberculosis. Some species of the mycobacterium tuberculosis complex mtbc, particularly mycobacterium tuberculosis, which causes human tuberculosis tb, are the first cause of death linked to a single pathogen worldwide. Drug resistance in mycobacterium tuberculosis microbewiki. Acid resistance in mycobacterium tuberculosis omar h. Signatures of selection at drug resistance loci in. Nathan,2 and sabine ehrt2 global alliance for tb drug development, new york, new york 5,1 and department of microbiology and immunology, weill cornell graduate school of medical sciences, new york, new york 100212 responses to acid have been studied extensively in enteric. Drugresistant tb develops when the antibiotics used to treat tb are misused or mismanaged, and it can spread. Because antibiotic treatment is one of the main tools for tuberculosis control, knowledge of mycobacterium tuberculosis drug resistance is an important component for the disease control strategy.
Any suspect colony confirmed as afb by microscopy was identified and tested for antibiotic resistance. Mycobacterium tuberculosis an overview sciencedirect topics. The effect of mutational events that lead to antibiotic resistant phenotypes may or may not have a predictable effect on the. Jun 12, 2009 tuberculosis infection kills nearly 2 million people a year and is the leading cause of death due to infectious diseases in adults and in aids patients.