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Clinical Microbiology Reviews Apr 2016Molecular typing has revolutionized epidemiological studies of infectious diseases, including those of a mycobacterial etiology. With the advent of fingerprinting... (Review)
Review
Molecular typing has revolutionized epidemiological studies of infectious diseases, including those of a mycobacterial etiology. With the advent of fingerprinting techniques, many traditional concepts regarding transmission, infectivity, or pathogenicity of mycobacterial bacilli have been revisited, and their conventional interpretations have been challenged. Since the mid-1990s, when the first typing methods were introduced, a plethora of other modalities have been proposed. So-called molecular epidemiology has become an essential subdiscipline of modern mycobacteriology. It serves as a resource for understanding the key issues in the epidemiology of tuberculosis and other mycobacterial diseases. Among these issues are disclosing sources of infection, quantifying recent transmission, identifying transmission links, discerning reinfection from relapse, tracking the geographic distribution and clonal expansion of specific strains, and exploring the genetic mechanisms underlying specific phenotypic traits, including virulence, organ tropism, transmissibility, or drug resistance. Since genotyping continues to unravel the biology of mycobacteria, it offers enormous promise in the fight against and prevention of the diseases caused by these pathogens. In this review, molecular typing methods for Mycobacterium tuberculosis and nontuberculous mycobacteria elaborated over the last 2 decades are summarized. The relevance of these methods to the epidemiological investigation, diagnosis, evolution, and control of mycobacterial diseases is discussed.
Topics: Bacterial Typing Techniques; Humans; Molecular Epidemiology; Molecular Typing; Mycobacterium; Mycobacterium Infections; Mycobacterium tuberculosis
PubMed: 26912567
DOI: 10.1128/CMR.00055-15 -
Microbiology Spectrum Apr 2022Pathogenic intracellular mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium avium, which cause lung diseases, can grow in macrophages. Extracellular...
Pathogenic intracellular mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium avium, which cause lung diseases, can grow in macrophages. Extracellular mycobacteria have been reported in the lungs, blood, and sputum of patients, indicating the involvement of these pathogens in disease progression. Erythrocytes are involved in the symptoms associated with pulmonary mycobacterial diseases, such as bloody sputum and hemoptysis; however, little attention has been paid to the role of erythrocytes in mycobacterial diseases. Herein, we found that Mycobacterium avium subsp. (MAH) and Mycobacterium intracellulare colocalized with erythrocytes at the sites of lung infection, inside capillaries and necrotic areas of granulomas, using histopathological examinations. Electron microscopy showed that MAH adhered and entered human erythrocytes when they were cocultured . MAH adhered to erythrocytes through complement receptor 1 and cell-surface sialo-glycoproteins. Importantly, MAH grew vigorously without causing any pronounced damage to erythrocytes. This erythrocyte-mediated enhancement of MAH growth occurred extracellularly depending on its direct attachment to erythrocytes. In contrast, MAH failed to multiply inside erythrocytes. Similarly, erythrocytes augmented the growth of other pathogenic mycobacteria, such as M. intracellulare and M. tuberculosis. THP-1 cell-derived human macrophages preferentially phagocytosed erythrocytes that were attached to mycobacteria (compared to bacteria alone), suggesting that erythrocyte-attached mycobacteria are an efficient infectious source for macrophages. Our findings provide new insights into the pathogenesis of mycobacterial diseases and offer an alternative and useful strategy for treating mycobacterial disease. Pathogenic mycobacteria, such as Mycobacterium tuberculosis, Mycobacterium avium subsp. (MAH), and Mycobacterium intracellulare, cause pulmonary infections as intracellular parasites of lung macrophages and epithelial cells. Here, using histopathological examinations we found that MAH and M. intracellulare colocalized with erythrocytes in lung infection sites. Subsequent studies demonstrated that direct interaction with erythrocytes enhances the extracellular proliferation of mycobacteria based on the following results: 1. MAH adhered and invaded human erythrocytes upon coculture ; 2. MAH adhered to erythrocytes through complement receptor 1 and cell-surface sialo-glycoproteins; 3. MAH rapidly proliferated when directly attached to erythrocytes but not within them; 4. other mycobacteria, such as M. intracellulare and M. tuberculosis, also proliferated in the same way as MAH. The finding that pathogenic mycobacteria grow extracellularly in an erythrocyte-dependent manner is of considerable clinical importance for understanding disease progression and latent infection.
Topics: Disease Progression; Erythrocytes; Glycoproteins; Humans; Mycobacterium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium tuberculosis; Receptors, Complement; Tuberculosis
PubMed: 35293805
DOI: 10.1128/spectrum.02454-21 -
FEMS Immunology and Medical Microbiology Nov 2006The continuous evolution of mycobacterial taxonomy may represent a source of confusion for laboratories and clinicians. Apart from the obvious pathogenic strains of the... (Review)
Review
The continuous evolution of mycobacterial taxonomy may represent a source of confusion for laboratories and clinicians. Apart from the obvious pathogenic strains of the Mycobacterium tuberculosis complex, Mycobacterium leprae and Mycobacterium ulcerans, the role of other mycobacteria may be associated with varying conditions ranging from contamination to specific disease processes. Of the more than 120 mycobacterial species recognized currently, very few have not been reported as pathogenic in humans or animals. Although the attempt to keep pace with the steadily increasing number of mycobacterial species seems hopeless, a careful review of the recent literature relevant to the newly described species may be advantageous. The aim of this present update is to provide epidemiological and clinical information along with major phenotypic and genotypic characteristics of the species described in the last 3 years.
Topics: Animals; Genotype; Humans; Mycobacterium; Mycobacterium Infections; Phenotype; Phylogeny
PubMed: 17064273
DOI: 10.1111/j.1574-695X.2006.00123.x -
Frontiers in Immunology 2022complex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental... (Review)
Review
complex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental media such as soil as well as in domestic and natural waters. MAC is a primary causative agent of NTM-lung disease that threaten immunocompromised or structural lung disease patients. The incidence and the prevalence of infection have been reduced, while MAC infections and mortality rates have increased, making it a cause of global health concern. The emergence of drug resistance and the side effects of long-term drug use have led to a poor outcome of treatment regimens against MAC infections. Therefore, the development of host-directed therapy (HDT) has recently gained interest, aiming to accelerate mycobacterial clearance and reversing lung damage by employing the immune system using a novel adjuvant strategy to improve the clinical outcome of MAC infection. Therefore, in this review, we discuss the innate immune responses that contribute to MAC infection focusing on macrophages, chief innate immune cells, and host susceptibility factors in patients. We also discuss potential HDTs that can act on the signaling pathway of macrophages, thereby contributing to antimycobacterial activity as a part of the innate immune response during MAC infection. Furthermore, this review provides new insights into MAC infection control that modulates and enhances macrophage function, promoting host antimicrobial activity in response to potential HDTs and thus presenting a deeper understanding of the interactions between macrophages and MACs during infection.
Topics: Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Macrophages; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Lung Diseases
PubMed: 36505429
DOI: 10.3389/fimmu.2022.931876 -
Microbiology Spectrum Aug 2014The cell wall of Mycobacterium tuberculosis is unique in that it differs significantly from those of both Gram-negative and Gram-positive bacteria. The thick,... (Review)
Review
The cell wall of Mycobacterium tuberculosis is unique in that it differs significantly from those of both Gram-negative and Gram-positive bacteria. The thick, carbohydrate- and lipid-rich cell wall with distinct lipoglycans enables mycobacteria to survive under hostile conditions such as shortage of nutrients and antimicrobial exposure. The key features of this highly complex cell wall are the mycolyl-arabinogalactan-peptidoglycan (mAGP)-based and phosphatidyl-myo-inositol-based macromolecular structures, with the latter possessing potent immunomodulatory properties. These structures are crucial for the growth, viability, and virulence of M. tuberculosis and therefore are often the targets of effective chemotherapeutic agents against tuberculosis. Over the past decade, sophisticated genomic and molecular tools have advanced our understanding of the primary structure and biosynthesis of these macromolecules. The availability of the full genome sequences of various mycobacterial species, including M. tuberculosis, Mycobacterium marinum, and Mycobacterium bovis BCG, have greatly facilitated the identification of large numbers of drug targets and antigens specific to tuberculosis. Techniques to manipulate mycobacteria have also improved extensively; the conditional expression-specialized transduction essentiality test (CESTET) is currently used to determine the essentiality of individual genes. Finally, various biosynthetic assays using either purified proteins or synthetic cell wall acceptors have been developed to study enzyme function. This article focuses on the recent advances in determining the structural details and biosynthesis of arabinogalactan, lipoarabinomannan, and related glycoconjugates.
Topics: Antitubercular Agents; Biosynthetic Pathways; Galactans; Genome, Bacterial; Lipopolysaccharides; Molecular Biology; Mycobacterium
PubMed: 26104198
DOI: 10.1128/microbiolspec.MGM2-0013-2013 -
Microbiology Spectrum Apr 2014Efforts to understand the molecular basis of mycobacterial gene regulation are dominated by a protein-centric view. However, there is a growing appreciation that... (Review)
Review
Efforts to understand the molecular basis of mycobacterial gene regulation are dominated by a protein-centric view. However, there is a growing appreciation that noncoding RNA, i.e., RNA that is not translated, plays a role in a wide variety of molecular mechanisms. Noncoding RNA comprises rRNA, tRNA, 4.5S RNA, RnpB, and transfer-messenger RNA, as well as a vast population of regulatory RNA, often dubbed "the dark matter of gene regulation." The regulatory RNA species comprise 5' and 3' untranslated regions and a rapidly expanding category of transcripts with the ability to base-pair with mRNAs or to interact with proteins. Regulatory RNA plays a central role in the bacterium's response to changes in the environment, and in this article we review emerging information on the presence and abundance of different types of noncoding RNA in mycobacteria.
Topics: Adaptation, Physiological; Gene Expression Regulation, Bacterial; Mycobacterium; RNA, Untranslated
PubMed: 26105815
DOI: 10.1128/microbiolspec.MGM2-0029-2013 -
Antonie Van Leeuwenhoek Jul 2018The taxonomic positions of two fast growing mycobacteria (CECT 8778 and CECT 8779) were established using a polyphasic approach. The strains were shown to have...
The taxonomic positions of two fast growing mycobacteria (CECT 8778 and CECT 8779) were established using a polyphasic approach. The strains were shown to have chemotaxonomic, cultural and morphological properties consistent with their classification in the genus Mycobacterium. Multi-locus sequence analyses (MLSA) show that strain CECT 8778 forms a well-supported clade together with the type strains of Mycobacterium aurum, Mycobacterium austroafricanum and Mycobacterium vanbaalenii while strain CECT 8779 presents as a distinct branch that is well separated from its near phylogenetic neighbours; it is also apparent from the MLSA genetic distances that these strains are most closely related to the type strains of Mycobacterium mageritense and M. vanbaalenii, respectively. Digital DNA:DNA hybridization and average nucleotide identity values between each of the strains and its close phylogenetic neighbour are below the 70 and 96% threshold values for definition of prokaryotic species; these results are underpinned by corresponding phenotypic data. Based upon the consensus of the phenotypic and phylogenetic analyses, it can be concluded that the two strains represent novel species within the genus Mycobacterium for which the following names are proposed: Mycobacterium neglectum sp. nov., with the type strain CECT 8778 (BN 3150 = DSM 44756) and Mycobacterium palauense sp. nov., with the type strain CECT 8779 (= DSM 44914).
Topics: DNA, Bacterial; Multilocus Sequence Typing; Mycobacterium; Nucleic Acid Hybridization; Phylogeny; RNA, Ribosomal, 16S
PubMed: 29404824
DOI: 10.1007/s10482-018-1029-5 -
Journal of Clinical Microbiology May 2019This minireview provides an update on recent taxonomic changes for the genus with an emphasis on newly identified species isolated from humans or associated with human... (Review)
Review
This minireview provides an update on recent taxonomic changes for the genus with an emphasis on newly identified species isolated from humans or associated with human disease.
Topics: Humans; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Phylogeny
PubMed: 30602442
DOI: 10.1128/JCM.01408-18 -
International Journal of Molecular... Jul 2021The mycobacterial cell wall is composed of large amounts of lipids with varying moieties. Some mycobacteria species hijack host cells and promote lipid droplet... (Review)
Review
The mycobacterial cell wall is composed of large amounts of lipids with varying moieties. Some mycobacteria species hijack host cells and promote lipid droplet accumulation to build the cellular environment essential for their intracellular survival. Thus, lipids are thought to be important for mycobacteria survival as well as for the invasion, parasitization, and proliferation within host cells. However, their physiological roles have not been fully elucidated. Recent studies have revealed that mycobacteria modulate the peroxisome proliferator-activated receptor (PPAR) signaling and utilize host-derived triacylglycerol (TAG) and cholesterol as both nutrient sources and evasion from the host immune system. In this review, we discuss recent findings that describe the activation of PPARs by mycobacterial infections and their role in determining the fate of bacilli by inducing lipid metabolism, anti-inflammatory function, and autophagy.
Topics: Animals; Autophagy; Cholesterol; Humans; Lipid Metabolism; Mycobacterium; Mycobacterium Infections; Peroxisome Proliferator-Activated Receptors; Signal Transduction
PubMed: 34299217
DOI: 10.3390/ijms22147597 -
Journal of Clinical Microbiology Jan 2020infection and nontuberculous mycobacteria (NTM) infections exhibit similar clinical symptoms; however, the therapies for these two types of infections are different....
infection and nontuberculous mycobacteria (NTM) infections exhibit similar clinical symptoms; however, the therapies for these two types of infections are different. Therefore, the rapid and accurate identification of and NTM species is very important for the control of tuberculosis and NTM infections. In the present study, a Cas12a/guide RNA (gRNA)-based platform was developed to identify and most NTM species. By designing species-specific gRNA probes targeting the sequence, a Cas12a/gRNA-based platform successfully identified and six major NTM species (, , , , , and ) without cross-reactivity. In a blind assessment, a total of 72 out of 73 clinical isolates were correctly identified, which is consistent with previous sequencing results. These results suggest that the Cas12a/gRNA-based platform is a promising tool for the rapid, accurate, and cost-effective identification of both and NTM species.
Topics: Bacterial Proteins; CRISPR-Associated Proteins; CRISPR-Cas Systems; Endodeoxyribonucleases; Humans; Mycobacterium; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; RNA Probes; RNA, Guide, CRISPR-Cas Systems; RNA, Ribosomal, 16S; Sensitivity and Specificity; Tuberculosis
PubMed: 31723010
DOI: 10.1128/JCM.01368-19