Abstract:Tuberculosis continues to be the main cause of death from a single infectious agent in developing countries. The causative agent, Mycobacterium tuberculosis, is thought to have diverged from its common ancestor as recently as 15,000 years ago. Subsequently, various genetic elements have evolved over time at different rates and can be used to elucidate patterns of infection. When individual elements are studied within genetic families, very low rates of variation are observed for almost every marker. For exampl… Show more
“…However, there was some association of specific IS6110-RFLP patterns with disease presentation, suggesting that some strains may have the ability to disseminate more easily than others. Similarly, studies performed in Vietnam reported that the Euro-American lineage (corresponding to the modern group 2 strains [5]) associated with radiographically detected lung consolidation in pulmonary TB patients was more likely to result in pulmonary TB than meningeal TB (59) and less likely to cause extrapulmonary disease (12). In The Gambia, contacts exposed to Beijing strains were most likely to develop TB disease (14).…”
Section: Discussionmentioning
confidence: 92%
“…The strain distribution was similar to that described in a previous study (24). Then, for the analysis, we considered the phylogeny described elsewhere (5,9), where the M. tuberculosis strains were divided into an "ancient" strain group (spoligotypes of the East African-Indian [EAI] family) and a "modern" strain group, with modern group 1 including the Beijing and Central Asian (CAS) families and modern group 2 containing the T (undefined family), Haarlem, LAM, U, X, and S families (Fig. 1B).…”
The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop tuberculosis (TB), though many may become latently infected. More precise measurement of the human immune response to M. tuberculosis infection may help us understand this difference and potentially identify those subjects most at risk of developing active disease. Gamma interferon (IFN-␥) production has been widely used as a proxy marker to study infection and to examine the human immune response to specific M. tuberculosis antigens. It has been suggested that genetically distinct M. tuberculosis strains may invoke different immune responses, although how these differences influence the immune responses and clinical outcome in human tuberculosis is still poorly understood. We therefore evaluated the antigen-specific IFN-␥ production responses in peripheral blood mononuclear cells from two cohorts of subjects recruited in Antananarivo Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major cause of global morbidity and mortality throughout the world. It is estimated that there are in excess of new 8 million cases of TB each year, and this represents just the tip of the iceberg. Infection with M. tuberculosis leads to clinically active TB in about 5 to 10% of exposed individuals. A much higher proportion of exposed individuals apparently become latently infected, and these individuals may remain noninfectious and symptom free for years. Approximately one-third of the world population is thought to be latently infected with M. tuberculosis. However, under some circumstances (in about 5% of the latently infected people), the host immune response is perturbed and latent M. tuberculosis infection may develop into clinically active TB (52). This process is most prominent in individuals coinfected with human immunodeficiency virus (HIV), but it can also occur with impairment of the immune system associated with old age, malnutrition, anti-inflammatory drug treatment, etc. Reactivation of latent disease is thought to contribute roughly half of all TB cases, and thus, understanding the factors controlling the development of acute primary TB or latent infection is crucial to TB control (64).Gamma interferon (IFN-␥) production has been widely used to study infection and to examine the human immune response to specific M. tuberculosis antigens. The 6-kDa early secreted antigenic target (ESAT-6) antigen, encoded by genes located within region of difference 1 (RD1) of the M. tuberculosis genome, is much more specific for M. tuberculosis than purified protein derivative (PPD), as these genes were deleted from M. bovis in the development of BCG substrains or are not found in most environmental mycobacteria (29,53). Some studies showed that the level of IFN-␥ release in response to ESAT-6 could identify TB contacts at risk of developing active disease after recent infection (3,18,30). CFP7 or TB10.4 is an immunodominant antigen recognized by TB patients and M. bovis BCG-vaccinated subjects, while ESAT-6 is specific to TB pa-
“…However, there was some association of specific IS6110-RFLP patterns with disease presentation, suggesting that some strains may have the ability to disseminate more easily than others. Similarly, studies performed in Vietnam reported that the Euro-American lineage (corresponding to the modern group 2 strains [5]) associated with radiographically detected lung consolidation in pulmonary TB patients was more likely to result in pulmonary TB than meningeal TB (59) and less likely to cause extrapulmonary disease (12). In The Gambia, contacts exposed to Beijing strains were most likely to develop TB disease (14).…”
Section: Discussionmentioning
confidence: 92%
“…The strain distribution was similar to that described in a previous study (24). Then, for the analysis, we considered the phylogeny described elsewhere (5,9), where the M. tuberculosis strains were divided into an "ancient" strain group (spoligotypes of the East African-Indian [EAI] family) and a "modern" strain group, with modern group 1 including the Beijing and Central Asian (CAS) families and modern group 2 containing the T (undefined family), Haarlem, LAM, U, X, and S families (Fig. 1B).…”
The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop tuberculosis (TB), though many may become latently infected. More precise measurement of the human immune response to M. tuberculosis infection may help us understand this difference and potentially identify those subjects most at risk of developing active disease. Gamma interferon (IFN-␥) production has been widely used as a proxy marker to study infection and to examine the human immune response to specific M. tuberculosis antigens. It has been suggested that genetically distinct M. tuberculosis strains may invoke different immune responses, although how these differences influence the immune responses and clinical outcome in human tuberculosis is still poorly understood. We therefore evaluated the antigen-specific IFN-␥ production responses in peripheral blood mononuclear cells from two cohorts of subjects recruited in Antananarivo Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major cause of global morbidity and mortality throughout the world. It is estimated that there are in excess of new 8 million cases of TB each year, and this represents just the tip of the iceberg. Infection with M. tuberculosis leads to clinically active TB in about 5 to 10% of exposed individuals. A much higher proportion of exposed individuals apparently become latently infected, and these individuals may remain noninfectious and symptom free for years. Approximately one-third of the world population is thought to be latently infected with M. tuberculosis. However, under some circumstances (in about 5% of the latently infected people), the host immune response is perturbed and latent M. tuberculosis infection may develop into clinically active TB (52). This process is most prominent in individuals coinfected with human immunodeficiency virus (HIV), but it can also occur with impairment of the immune system associated with old age, malnutrition, anti-inflammatory drug treatment, etc. Reactivation of latent disease is thought to contribute roughly half of all TB cases, and thus, understanding the factors controlling the development of acute primary TB or latent infection is crucial to TB control (64).Gamma interferon (IFN-␥) production has been widely used to study infection and to examine the human immune response to specific M. tuberculosis antigens. The 6-kDa early secreted antigenic target (ESAT-6) antigen, encoded by genes located within region of difference 1 (RD1) of the M. tuberculosis genome, is much more specific for M. tuberculosis than purified protein derivative (PPD), as these genes were deleted from M. bovis in the development of BCG substrains or are not found in most environmental mycobacteria (29,53). Some studies showed that the level of IFN-␥ release in response to ESAT-6 could identify TB contacts at risk of developing active disease after recent infection (3,18,30). CFP7 or TB10.4 is an immunodominant antigen recognized by TB patients and M. bovis BCG-vaccinated subjects, while ESAT-6 is specific to TB pa-
“…SNPs within this gene could likely be an indication of common evolutionary ancestor with environmental isolates. Similarity, SNPs in cytochrome P450 enzymes (Table 5) that catalyze mixed oxidation of hydrophobic compounds associated with free-living saprophyte (Arnold, 2007), another indication of a common environmental ancestor for M. ap . Finally, genes encoding cytochrome P450 were shown to play a role in the persistence of M. tuberculosis in tissues (McLean et al, 2010).…”
Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of Johne’s disease, infects many farmed ruminants, wild-life animals, and recently isolated from humans. To better understand the molecular pathogenesis of these infections, we analyzed the whole-genome sequences of several M. ap and M. avium subspecies avium (M. avium) isolates to gain insights into genomic diversity associated with variable hosts and environments. Using Next-generation sequencing technology, all six M. ap isolates showed a high percentage of similarity (98%) to the reference genome sequence of M. ap K-10 isolated from cattle. However, two M. avium isolates (DT 78 and Env 77) showed significant sequence diversity (only 87 and 40% similarity, respectively) compared to the reference strain M. avium 104, a reflection of the wide environmental niches of this group of mycobacteria. Within the M. ap isolates, genomic rearrangements (insertions/deletions) were not detected, and only unique single nucleotide polymorphisms (SNPs) were observed among M. ap isolates. While more of the SNPs (~100) in M. ap genomes were non-synonymous, a total of ~6,000 SNPs were detected among M. avium genomes, most of them were synonymous suggesting a differential selective pressure between M. ap and M. avium isolates. In addition, SNPs-based phylo-genomics had a enough discriminatory power to differentiate between isolates from different hosts but yet suggesting a bovine source of infection to other animals examined in this study. Interestingly, the human isolate (M. ap 4B) was closely related to a M. ap isolate from a dairy facility, suggesting a common source of infection. Overall, the identified phylo-genomes further supported the idea of a common ancestor to both M. ap and M. avium isolates. Genome-wide analysis described here could provide a strong foundation for a population genetic structure that could be useful for the analysis of mycobacterial evolution and for the tracking of Johne’s disease transmission among animals.
“…Finally, the acquisition of drug resistance depends on the MT subgroup. Beijing type strains are relatively abundant among MDR and XDR strains (for a review of the other features of such strains, see [3]). An attempt was made to hypothesize that the fact that such strains tend to acquire MDR is associated with their higher mutability, but the frequency of spontaneous rifampi cin resistance mutations in vitro was the same as in other MT types [102].…”
Section: Tolerance and Latencymentioning
confidence: 99%
“…All of the MTC members are subspecies of one species, which is also termed MT. There are seven such subspecies (M. tuberculosis, M. africanum, M. bovis, M. caprae, M. pinnipedi, M. microti, and M. cannettii, also known as M. prototuberculosis), which have the same charac teristics of the 16S rRNA genes and differ only in structure of certain genome regions [2,3]. MT (earlier referred to as M. tuberculosis hominis) is the most sig nificant for medicine.…”
The review summarizes the data on the Mycobacterium tuberculosis mutations that lead to multi drug resistance (MDR) to various antibiotics. MDR strains arose over the past 30 years as a variety of antitu berculosis drugs were introduced in medicine, and they largely discount the results of chemotherapy for tuberculosis. The most dangerous of them are strains with extensive drug resistance (XDR), which are resis tant to four or five different drugs on average. The molecular mechanisms that make a strain resistant are con sidered. XDR and MDR strains result from successive and usually independent resistance mutations, which arise in various regions of the mycobacterial genome. In addition, the formation of resistant strains is affected by the phenomenon of tolerance and mycobacterial latency in infected tissues.
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