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Clinical Microbiology Reviews Jan 2018Humans encounter mycobacterial species due to their ubiquity in different environmental niches. In many individuals, pathogenic mycobacterial species may breach our... (Review)
Review
Humans encounter mycobacterial species due to their ubiquity in different environmental niches. In many individuals, pathogenic mycobacterial species may breach our first-line barrier defenses of the innate immune system and modulate the activation of phagocytes to cause disease of the respiratory tract or the skin and soft tissues, sometimes resulting in disseminated infection. Cutaneous mycobacterial infections may cause a wide range of clinical manifestations, which are divided into four main disease categories: (i) cutaneous manifestations of infection, (ii) Buruli ulcer caused by and other related slowly growing mycobacteria, (iii) leprosy caused by and , and (iv) cutaneous infections caused by rapidly growing mycobacteria. Clinically, cutaneous mycobacterial infections present with widely different clinical presentations, including cellulitis, nonhealing ulcers, subacute or chronic nodular lesions, abscesses, superficial lymphadenitis, verrucous lesions, and other types of findings. Mycobacterial infections of the skin and subcutaneous tissue are associated with important stigma, deformity, and disability. Geography-based environmental exposures influence the epidemiology of cutaneous mycobacterial infections. Cutaneous tuberculosis exhibits different clinical phenotypes acquired through different routes, including via extrinsic inoculation of the tuberculous bacilli and dissemination to the skin from other sites, or represents hypersensitivity reactions to infection. In many settings, leprosy remains an important cause of neurological impairment, deformity, limb loss, and stigma. , a mycobacterial species related to , is linked to diffuse lepromatous leprosy of Lucio and Latapí. produces a mycolactone toxin that leads to subcutaneous tissue destruction and immunosuppression, resulting in deep ulcerations that often produce substantial disfigurement and disability. , a close relative of , is an important cause of cutaneous sporotrichoid nodular lymphangitic lesions. Among patients with advanced immunosuppression, , the complex, and may cause cutaneous or disseminated disease. Rapidly growing mycobacteria, including the group, , and , are increasingly recognized pathogens in cutaneous infections associated particularly with plastic surgery and cosmetic procedures. Skin biopsies of cutaneous lesions to identify acid-fast staining bacilli and cultures represent the cornerstone of diagnosis. Additionally, histopathological evaluation of skin biopsy specimens may be useful in identifying leprosy, Buruli ulcer, and cutaneous tuberculosis. Molecular assays are useful in some cases. The treatment for cutaneous mycobacterial infections depends on the specific pathogen and therefore requires a careful consideration of antimicrobial choices based on official treatment guidelines.
Topics: Animals; Dermatitis; Humans; Mycobacterium; Mycobacterium Infections
PubMed: 30429139
DOI: 10.1128/CMR.00069-18 -
Clinical Infectious Diseases : An... Aug 2020Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and...
Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
Topics: Adult; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium kansasii; Nontuberculous Mycobacteria
PubMed: 32797222
DOI: 10.1093/cid/ciaa1125 -
Nature Reviews. Microbiology Oct 2015Extracellular vesicles (EVs) are produced by all domains of life. In Gram-negative bacteria, EVs are produced by the pinching off of the outer membrane; however, how EVs... (Review)
Review
Extracellular vesicles (EVs) are produced by all domains of life. In Gram-negative bacteria, EVs are produced by the pinching off of the outer membrane; however, how EVs escape the thick cell walls of Gram-positive bacteria, mycobacteria and fungi is still unknown. Nonetheless, EVs have been described in a variety of cell-walled organisms, including Staphylococcus aureus, Mycobacterium tuberculosis and Cryptococcus neoformans. These EVs contain varied cargo, including nucleic acids, toxins, lipoproteins and enzymes, and have important roles in microbial physiology and pathogenesis. In this Review, we describe the current status of vesiculogenesis research in thick-walled microorganisms and discuss the cargo and functions associated with EVs in these species.
Topics: Extracellular Vesicles; Fungi; Gram-Positive Bacteria; Host-Pathogen Interactions; Mycobacterium
PubMed: 26324094
DOI: 10.1038/nrmicro3480 -
Clinical Microbiology Reviews Oct 2014Nontuberculous mycobacteria (NTM) are present in the environment, mainly in water, and are occasionally responsible for opportunistic infections in humans. Despite the... (Review)
Review
Nontuberculous mycobacteria (NTM) are present in the environment, mainly in water, and are occasionally responsible for opportunistic infections in humans. Despite the fact that NTM are characterized by a moderate pathogenicity, the diseases caused by NTM at various body sites are increasing on a worldwide level. Among over 150 officially recognized NTM species, only two or three dozen are familiar to clinicians, and even to most microbiologists. In this paper, approximately 50 new species described in the last 8 years are reviewed, and their role in human infections is assessed on the basis of reported clinical cases. The small number of reports concerning most of the "new" mycobacterial species is responsible for the widespread conviction that they are very rare. Their role is actually largely underestimated, mainly because they often remain unrecognized and misidentified. Aiming to minimize such bias, emphasis has been placed on more common identification pitfalls. Together with new NTM, new members of the Mycobacterium tuberculosis complex described in the last few years are also an object of the present review.
Topics: Humans; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Phylogeny
PubMed: 25278573
DOI: 10.1128/CMR.00035-14 -
Frontiers in Immunology 2022Non-tuberculous mycobacteria (NTM) are a heterogeneous group of originally environmental organi3sms, increasingly recognized as pathogens with rising prevalence... (Review)
Review
Non-tuberculous mycobacteria (NTM) are a heterogeneous group of originally environmental organi3sms, increasingly recognized as pathogens with rising prevalence worldwide. Knowledge of NTM's mechanisms of virulence is lacking, as molecular research of these bacteria is challenging, sometimes more than that of M. tuberculosis (Mtb), and far less resources are allocated to their investigation. While some of the virulence mechanisms are common to several mycobacteria including Mtb, others NTM species-specific. Among NTMs, Mycobacterium abscessus (Mabs) causes some of the most severe and difficult to treat infections, especially chronic pulmonary infections. Mabs survives and proliferates intracellularly by circumventing host defenses, using multiple mechanisms, many of which remain poorly characterized. Some of these immune-evasion mechanisms are also found in Mtb, including phagosome pore formation, inhibition of phagosome maturation, cytokine response interference and apoptosis delay. While much is known of the role of Mtb-secreted effector molecules in mediating the manipulation of the host response, far less is known of the secreted effector molecules in Mabs. In this review, we briefly summarize the knowledge of secreted effectors in Mtb (such as ESX secretion, SecA2, TAT and others), and draw the parallel pathways in Mabs. We also describe pathways that are unique to Mabs, differentiating it from Mtb. This review will assist researchers interested in virulence-associated secretion in Mabs by providing the knowledge base and framework for their studies.
Topics: Mycobacterium abscessus; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Phagosomes; Virulence
PubMed: 35880173
DOI: 10.3389/fimmu.2022.938895 -
Immunological Reviews May 2021Upon infection, mycobacteria, such as Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM), are recognized by host innate immune cells, triggering a... (Review)
Review
Upon infection, mycobacteria, such as Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM), are recognized by host innate immune cells, triggering a series of intracellular processes that promote mycobacterial killing. Mycobacteria, however, have developed multiple counter-strategies to persist and survive inside host cells. By manipulating host effector mechanisms, including phagosome maturation, vacuolar escape, autophagy, antigen presentation, and metabolic pathways, pathogenic mycobacteria are able to establish long-lasting infection. Counteracting these mycobacteria-induced host modifying mechanisms can be accomplished by host-directed therapeutic (HDT) strategies. HDTs offer several major advantages compared to conventional antibiotics: (a) HDTs can be effective against both drug-resistant and drug-susceptible bacteria, as well as potentially dormant mycobacteria; (b) HDTs are less likely to induce bacterial drug resistance; and (c) HDTs could synergize with, or shorten antibiotic treatment by targeting different pathways. In this review, we will explore host-pathogen interactions that have been identified for Mtb for which potential HDTs impacting both innate and adaptive immunity are available, and outline those worthy of future research. We will also discuss possibilities to target NTM infection by HDT, although current knowledge regarding host-pathogen interactions for NTM is limited compared to Mtb. Finally, we speculate that combinatorial HDT strategies can potentially synergize to achieve optimal mycobacterial host immune control.
Topics: Anti-Bacterial Agents; Autophagy; Host-Pathogen Interactions; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 33565103
DOI: 10.1111/imr.12951 -
Journal of Clinical Microbiology Feb 2017This article summarizes the most recent (since 2012) taxonomic changes in the genus Mycobacterium Only those mycobacteria that have been isolated from human specimens... (Review)
Review
This article summarizes the most recent (since 2012) taxonomic changes in the genus Mycobacterium Only those mycobacteria that have been isolated from human specimens are included in this summary.
Topics: Humans; Mycobacterium; Mycobacterium Infections
PubMed: 27927928
DOI: 10.1128/JCM.01287-16 -
Microbiology Spectrum Feb 2014Most mycobacterial species are harmless saprophytes, often found in aquatic environments. A few species seem to have evolved from this pool of environmental mycobacteria... (Review)
Review
Most mycobacterial species are harmless saprophytes, often found in aquatic environments. A few species seem to have evolved from this pool of environmental mycobacteria into major human pathogens, such as Mycobacterium tuberculosis, the agent of tuberculosis, Mycobacterium leprae, the leprosy bacillus, and Mycobacterium ulcerans, the agent of Buruli ulcer. While the pathogenicity of M. ulcerans relates to the acquisition of a large plasmid encoding a polyketide-derived toxin, the molecular mechanisms by which M. leprae or M. tuberculosis have evolved to cause disease are complex and involve the interaction between the pathogen and the host. Here we focus on M. tuberculosis and closely related mycobacteria and discuss insights gained from recent genomic and functional studies. Comparison of M. tuberculosis genome data with sequences from nontuberculous mycobacteria, such as Mycobacterium marinum or Mycobacterium kansasii, provides a perception of the more distant evolution of M. tuberculosis, while the recently accomplished genome sequences of multiple tubercle bacilli with smooth colony morphology, named Mycobacterium canettii, have allowed the ancestral gene pool of tubercle bacilli to be estimated. The resulting findings are instrumental for our understanding of the pathogenomic evolution of tuberculosis-causing mycobacteria. Comparison of virulent and attenuated members of the M. tuberculosis complex has further contributed to identification of a specific secretion pathway, named ESX or Type VII secretion. The molecular machines involved are key elements for mycobacterial pathogenicity, strongly influencing the ability of M. tuberculosis to cope with the immune defense mounted by the host.
Topics: Computational Biology; Evolution, Molecular; Genome, Bacterial; Humans; Mycobacterium; Tuberculosis; Virulence Factors
PubMed: 26082120
DOI: 10.1128/microbiolspec.MGM2-0025-2013 -
Journal of Bacteriology Apr 2021Mycobacteria have unique cell envelopes, surface properties, and growth dynamics, which all play a part in the ability of these important pathogens to infect, evade host... (Review)
Review
Mycobacteria have unique cell envelopes, surface properties, and growth dynamics, which all play a part in the ability of these important pathogens to infect, evade host immunity, disseminate, and resist antibiotic challenges. Recent atomic force microscopy (AFM) studies have brought new insights into the nanometer-scale ultrastructural, adhesive, and mechanical properties of mycobacteria. The molecular forces with which mycobacterial adhesins bind to host factors, like heparin and fibronectin, and the hydrophobic properties of the mycomembrane have been unraveled by AFM force spectroscopy studies. Real-time correlative AFM and fluorescence imaging have delineated a complex interplay between surface ultrastructure, tensile stresses within the cell envelope, and cellular processes leading to division. The unique capabilities of AFM, which include subdiffraction-limit topographic imaging and piconewton force sensitivity, have great potential to resolve important questions that remain unanswered on the molecular interactions, surface properties, and growth dynamics of this important class of pathogens.
Topics: Adhesins, Bacterial; Anti-Bacterial Agents; Cell Membrane; Hydrophobic and Hydrophilic Interactions; Membrane Lipids; Microscopy, Atomic Force; Mycobacterium; Surface Properties
PubMed: 33468595
DOI: 10.1128/JB.00547-20 -
Microbiology Spectrum Oct 2014Bacteria have a natural propensity to grow as sessile, matrix-encapsulated, multicellular communities called biofilms. Formation of biofilms proceeds through genetically... (Review)
Review
Bacteria have a natural propensity to grow as sessile, matrix-encapsulated, multicellular communities called biofilms. Formation of biofilms proceeds through genetically programmed, distinct developmental stages signaled by intricate networks of communication among the constituent population and their environment. Growing in the complex and heterogeneous microenvironments of biofilms, the resident bacteria acquire unique phenotypes that are generally not associated with their planktonic counterparts. Most notable among these is an extraordinary level of tolerance to a variety of environmental stresses, including antibiotics. Although mycobacteria have long been observed to spontaneously form complex multicellular structures in vitro, it has only recently become apparent that these structures are not only formed through dedicated genetic pathways but are also tolerant to antibiotics. In this article, we review the recent advances in the understanding of mycobacterial biofilms in vitro. We further consider the possible linkage between biofilm-like lifestyles and characteristic persistence of mycobacterial infections against host-defense mechanisms as well as antibiotics.
Topics: Antitubercular Agents; Biofilms; Drug Tolerance; Immune Evasion; Mycobacterium
PubMed: 26104368
DOI: 10.1128/microbiolspec.MGM2-0004-2013