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Biochimie Oct 2017Phenolic glycolipids (PGL) are polyketide synthase products that are uniquely produced by a subset of pathogenic mycobacteria and are displayed at the bacterial cell... (Review)
Review
Phenolic glycolipids (PGL) are polyketide synthase products that are uniquely produced by a subset of pathogenic mycobacteria and are displayed at the bacterial cell surface, in a strategic position to interfere with host immune cells. Their expression has been associated with enhanced mycobacterial virulence in vivo, and suppression of the inflammatory responses of host phagocytes in vitro. In this review, we will present our current understanding of the mode of operation of PGL, along with functional evidence that demonstrates the evolutionary advantage conferred by PGL production for host cell invasion, intracellular persistence and evasion of host immune and bactericidal responses.
Topics: Animals; Glycolipids; Humans; Immunosuppressive Agents; Mycobacterium
PubMed: 28322927
DOI: 10.1016/j.biochi.2017.03.012 -
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 -
Revue Scientifique Et Technique... Apr 2001Tuberculosis, caused by Mycobacterium tuberculosis, and leprosy, caused by M. leprae, are diseases known since antiquity. In developing countries, tuberculosis is still... (Review)
Review
Tuberculosis, caused by Mycobacterium tuberculosis, and leprosy, caused by M. leprae, are diseases known since antiquity. In developing countries, tuberculosis is still the leading cause of mortality due to an infectious disease. Taxonomically, mycobacteria belong to the genus Mycobacterium, which is the single genus within the family of Mycobacteriaceae, in the order Actinomycetales. Actinomycetales include diverse micro-organisms, but mycobacteria and allied taxa are easily distinguished on the basis of the ability to synthesise mycolic acids. Mycobacterial species are traditionally differentiated on the basis of phenotypic characteristics, and the authors provide an updated list of the biochemical tests currently employed and the culture properties that help to discriminate among various species of mycobacteria. However, as the phenotypic characteristics do not allow precise identification of all species, recent molecular taxonomical approaches for mycobacterial classification and phylogeny are also described. Mycobacteria are also a leading cause of infection in various domesticated animals and wildlife. The authors briefly describe the mycobacteria involved in animal infections, the wildlife reservoirs and strategies to control bovine tuberculosis, and the use of molecular tools for diagnostics and epidemiology of mycobacterial infections in animals. The characteristic of intracellular parasitism is discussed, in addition to the fate of pathogenic mycobacteria that have the ability to grow inside phagosomes and phagolysosomes of infected host macrophages. The mycobacterial cell envelope, which is a complex tripartite structure containing a high proportion of lipids (approximately 30% to 40% of the total weight) could play a crucial role in the adaptation of mycobacteria to intracellular growth and survival, immune modulation and drug resistance.
Topics: Animals; Cattle; Classification; DNA Fingerprinting; DNA, Bacterial; Genotype; Humans; Mycobacterium; Mycobacterium Infections; Mycolic Acids; Phenotype; Phylogeny; Polymorphism, Restriction Fragment Length; Terminology as Topic; Tuberculosis, Bovine
PubMed: 11288513
DOI: 10.20506/rst.20.1.1265 -
BMC Infectious Diseases Mar 2024Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been...
BACKGROUND
Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been increasing in the United States and globally. The predominant clinically relevant species of NTM in the United States are Mycobacterium avium complex (MAC) species and Mycobacterium abscessus. With the development of rapid species identification methods for NTM (e.g. PCR probes), more testing for NTM is being conducted through commercial labs, such as Laboratory Corporation of America (Labcorp), which provides deidentified real-time testing data to the Centers for Disease Control (CDC) pursuant to a data sharing agreement. Because NTM lung infections are not reportable in most states, other data sources are key to understanding NTM testing patterns, positivity rates, and species distributions to track infection trends and identify clinical care needs.
METHODS
We obtained national Labcorp data for the period January 2019 through mid-April 2022. We subset the data to only respiratory samples sent for Acid Fast Bacilli (AFB) cultures. NTM positive results were defined as those which identified an NTM species and are not Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium gordonae.
RESULTS
Overall, 112,528 respiratory samples were sent for AFB testing during the study period; 26.3% were from the Southeast U.S., identified as HSS Region IV in the Labcorp dataset, and 23.0% were from the Pacific and South Pacific region (Region IX). The culture positive prevalence ranged from 20.2% in the Southeast to 9.2% in the East North Central region (Region V). In the Southeast US, M. abscessus prevalence was 4.0%. For MAC, the highest prevalence was observed in the Mountain region (Region VII) (13.5%) and the lowest proportion was in the East South Central region (7.3%, Region III). Among positive tests, the proportion which was MAC varied from 61.8% to 88.9% and was highest in the Northeast U.S. The proportion of positive samples which were M. abscessus ranged from 3.8% to 19.7% and was highest in the Southeast.
CONCLUSIONS
The Southeastern region of the U.S. has the highest rate of culture positivity in Labcorp tests for total NTM and, of all positive tests, the highest proportion of M. abscessus. These estimates may underrepresent the true number of M. abscessus infections because M. absesscus-specific probes are not commercially available and not all NTM testing in the United States is done by Labcorp. Analysis of real-time testing data from commercial laboratories may provide insights into risk factors for NTM culture positivity in 'hotspot' areas.
Topics: United States; Humans; Nontuberculous Mycobacteria; Mycobacterium avium Complex; Mycobacterium abscessus; Laboratories; Mycobacterium bovis; Opportunistic Infections
PubMed: 38448840
DOI: 10.1186/s12879-024-09059-9 -
Bioorganic & Medicinal Chemistry Letters Oct 2018From a high throughput screening of commercially available libraries against nontuberculous mycobacteria and Mycobacterium tuberculosis, numerous hits were identified...
From a high throughput screening of commercially available libraries against nontuberculous mycobacteria and Mycobacterium tuberculosis, numerous hits were identified with moderate activity. Extensive medicinal chemistry optimization has led to a series of potent benzothiazole amide antimycobacterial agents. Replacement of the adamantyl group with cyclohexyl derivatives and further development of this series resulted in an advanced lead compound, CRS400393, which demonstrated excellent potency and a mycobacteria-specific spectrum of activity. MIC values ranged from 0.03 to 0.12 μg/mL against Mycobacterium abscessus and other rapid-grower NTM, and 1-2 μg/mL against Mycobacterium avium complex. The preliminary mechanism of action studies suggested these agents may target MmpL3, a mycobacterial mycolic acid transporter. The series has demonstrated in vivo efficacy in a proof of concept mouse model of M. abscessus infection.
Topics: Amides; Animals; Anti-Bacterial Agents; Benzothiazoles; Drug Discovery; Mice; Microbial Sensitivity Tests; Mycobacterium; Species Specificity; Structure-Activity Relationship
PubMed: 30172617
DOI: 10.1016/j.bmcl.2018.08.026 -
Microbiology (Reading, England) Jun 2012The capacity to form microscopic cords (cording) of Mycobacterium species has been related to their virulence. The compounds responsible for cording are unknown, but a...
The capacity to form microscopic cords (cording) of Mycobacterium species has been related to their virulence. The compounds responsible for cording are unknown, but a recent study has shown that cording could be related to the fine structure of α-mycolic acids. This investigation attributes the need for a proximal cyclopropane in α-mycolic acids for cording in Mycobacterium tuberculosis and Mycobacterium bovis BCG and proposes cyclopropanases as good targets for new chemotherapeutic agents. As other Mycobacterium species in addition to M. tuberculosis and M. bovis form microscopic cords, it would be of major interest to know whether the relationship between proximal cyclopropanation of α-mycolic acids and cording could be extended to non-tuberculous mycobacteria. In this study, we have examined the correlation between the cording and cyclopropanation of α-mycolic acids in two species, Mycobacterium brumae and Mycobacterium fallax. Scanning electron microscopy images showed, for the first time to our knowledge, the fine structure of microscopic cords of M. brumae and M. fallax, confirming that these two species form true cords. Furthermore, NMR analysis performed on the same cording cultures corroborates the absence of cyclopropane rings in their α-mycolic acids. Therefore, we can conclude that the correlation between cording and cyclopropanation of α-mycolic acids cannot be extended to all mycobacteria. As M. brumae and M. fallax grow rapidly and have a simple pattern of mycolic acids (only α-unsaturated mycolic acids), we propose these two species as suitable models for the study of the role of mycolic acids in cording.
Topics: Cyclopropanes; Magnetic Resonance Spectroscopy; Molecular Structure; Mycobacterium; Mycolic Acids
PubMed: 22493302
DOI: 10.1099/mic.0.057919-0 -
Postepy Higieny I Medycyny... Apr 2014Mycolic acids are one of the basic structural elements of the cell wall of bacteria from Corynebacterineae suborder. These compounds are long-chain α-hydroxy β-alkyl... (Review)
Review
Mycolic acids are one of the basic structural elements of the cell wall of bacteria from Corynebacterineae suborder. These compounds are long-chain α-hydroxy β-alkyl fatty acids with two hydrocarbon chains: longer meromycolic and shorter α-chain meromycolic α-chain. The genus Mycobacterium is characterized by the presence of mycolic acids in length from 60 to 90 carbon atoms having a fully saturated α-chain with a defined length of 22, 24 or 26 carbon atoms. Current research indicates that not only the presence of mycolic acids in the cell wall of mycobacteria is essential for the virulence of mycobacteria. It is proved that the relationship between different types of mycolic acids, their length and the degree of cyclopropanation may vary depending on the stage of infection and mycobacterial culture conditions. At the same time it has been shown that some mycolic acid types are crucial for biofilm formation, antimycobacterial drug resistance or interactions with the immune system. Recent studies also indicate that analysis of mycolic acid profiles could be an alternative to conventional methods of diagnosis of diseases such as tuberculosis, leprosy or mycobacteriosis.
Topics: Biofilms; Cell Wall; Fatty Acids; Mycobacterium; Mycolic Acids; Virulence
PubMed: 24864086
DOI: 10.5604/17322693.1097425 -
Pneumologie (Stuttgart, Germany) Aug 2019The recognition, correct diagnosis and adequate clinical management of infections caused by atypical mycobacteria are challenging tasks in clinical practice. Invasive... (Review)
Review
The recognition, correct diagnosis and adequate clinical management of infections caused by atypical mycobacteria are challenging tasks in clinical practice. Invasive infections caused by , a member of the complex, have been increasingly reported over the past few years. Most infections occurred in patients who had undergone open-chest cardiothoracic surgery. Epidemiological and molecular studies showed that transmission of occurred through intraoperative aerosols derived from contaminated heater-cooler units, i. e. devices that are used to enable the extracardiac circuit in cardiothoracic surgery. Thus far, approximately 120 patient cases have been reported worldwide. The latency between exposure and onset of clinical symptoms may comprise several years. Clinical manifestations of infections include not only endocarditis and implant-associated infections, but also non-cardiac entities such as sarcoidosis-like symptoms, vertebral osteomyelitis and chorioretinitis. The pathogen can be detected in blood culture vials and in surgically obtained specimens from affected tissues, if specific microbiological tests for detection of mycobacteria are employed. There are no simple-to-use screening tests and a high clinical index of suspicion is thus mandatory in patients with previous exposure and compatible signs and symptoms. The successful treatment of infections requires the removal of infected devices and prolonged combination therapy with antimycobacterial drugs. This review summarises the clinical relevance, epidemiology, symptomatology, diagnosis and treatment of infections caused by , with a specific focus on pneumological aspects.
Topics: Humans; Mycobacterium; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Nontuberculous Mycobacteria
PubMed: 31075795
DOI: 10.1055/a-0872-8809 -
Revista Latino-americana de Enfermagem Feb 2013to evaluate evidence concerning sources or mechanisms of infection transmission of atypical mycobacteria associated with acupuncture, and the species causing infections. (Review)
Review
AIM
to evaluate evidence concerning sources or mechanisms of infection transmission of atypical mycobacteria associated with acupuncture, and the species causing infections.
METHOD
research was performed in December 2011 in the databases of LILACS, MEDLINE, EMBASE, OvidSP and the Cochrane Library, without restrictions regarding publication date, study type or language.
RESULTS
of the 16 publications, only one identified the contamination source: diluted glutaraldehyde solution used to clean equipment. Three established likely sources: towels, hot packs or boiling tank water, and the reuse of reprocessed needles. Four indicated possible sources: contaminated needles, reuse of personal needles, patient's skin colonized by mycobacteria and reuse of needles at different sites in the same patient. Eight of the studies did not mention the sources.
CONCLUSION
among 295 cases, M. abscessus was the pathological agent in over 96%. Well-established control practices for infection prevention should be implemented and adapted for complementary and alternative medicine.
Topics: Acupuncture Therapy; Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 23546331
DOI: 10.1590/s0104-11692013000100022