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Biofilm Dec 2023The genus includes some of the deadliest pathogens of History (), but most of the species within the genus are environmental microorganisms. Because some of these...
The genus includes some of the deadliest pathogens of History (), but most of the species within the genus are environmental microorganisms. Because some of these nontuberculous mycobacteria (NTM) species can be human pathogens, the study of these mycobacterial biofilms has increased during the last decades, and the interest in this issue increased as well as the growing number of patients with diseases caused by NTM. Different molecular mechanisms have been described, being especially well known the importance of glycopeptidolipids. Moreover, the knowledge of the extracellular matrix has shown important differences with other microorganisms, especially because of the presence of lipidic molecules as a key component of this structure. The clinical importance of mycobacterial biofilms has been described for many chronic diseases, especially lung diseases and implant-related ones, both and , and even in patients. Moreover, the biofilm-producing capacity has been proven also in , while its importance is not well understood. Biofilm studies have also shown the increasing resistance of mycobacteria in sessile form, and the importance of this resistance in the management of the patients is beyond doubt, being surgery necessary in some cases to cure the patients. Diagnosis of mycobacterial diseases is still based on culture-based techniques designed for the detection of . Molecular biology-based methods are also broadly used but again designed for tuberculosis diagnosis. Antimicrobial susceptibility testing is also well developed for tuberculosis, but only some species of NTM have standardized techniques for this purpose. New tools or approaches are necessary to treat these patients, whose importance is increasing, as the number of potential hosts is also increasing throughout the world.
PubMed: 36798742
DOI: 10.1016/j.bioflm.2023.100107 -
Cureus Dec 2023Hansen disease, known as Leprosy, is an infectious disease caused by . The disease was once thought to be highly contiguous, and patients with leprosy were treated... (Review)
Review
Hansen disease, known as Leprosy, is an infectious disease caused by . The disease was once thought to be highly contiguous, and patients with leprosy were treated poorly and had to face discrimination due to the gruesome disease's complications. , the bacterium causative of leprosy, can generally be found in the nine-banded armadillo. The bacterium is transmitted via aerosol droplets and broken skin-to-skin contact. Once M enters the body, it will target peripheral nerves and the lining mucosa of the skin and eyes, thus causing inflammation and tenderness of the affected area. Over time, this will lead to peripheral neuropathy and weakness of the affected body parts. Treatment of leprosy involves multi-drug combinations such as dapsone, rifampin, and clofazimine. Even though leprosy is curable, early detection and treatment are crucial to preventing irreversible damage and disabilities. Prevention measures include early detection, treatment regimen adherence, close contact prophylaxis, contact tracing, and community awareness. This review aims to provide the latest diagnostic and therapeutic recommendations for leprosy. It outlines the epidemiology, microbiology, clinical treatment, and immunological methods used to detect leprosy.
PubMed: 38179342
DOI: 10.7759/cureus.49954 -
ACS Infectious Diseases Feb 2024In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic... (Review)
Review
In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic nontuberculous mycobacteria (NTM). Among these, two neglected mycobacteria species of the Acinetobacter family, and , are the etiological agents of leprosy and Buruli ulcer infections, respectively, and fall under the broad umbrella of neglected tropical diseases (NTDs). Unfortunately, lackluster drug discovery efforts have been made against these pathogenic bacteria in the recent decade, resulting in the discovery of only a few countable hits and majorly repurposing anti-TB drug candidates such as telacebec (Q203), P218, and TB47 for current therapeutic interventions. Major ignorance in drug candidate identification might aggravate the dramatic consequences of rapidly spreading mycobacterial NTDs in the coming days. Therefore, this Review focuses on an up-to-date account of drug discovery efforts targeting selected druggable targets from both bacilli, including the accompanying challenges that have been identified and are responsible for the slow drug discovery. Furthermore, a succinct discussion of the all-new possibilities that could be alternative solutions to mitigate the neglected mycobacterial NTD burden and subsequently accelerate the drug discovery effort is also included. We anticipate that the state-of-the-art strategies discussed here may attract major attention from the scientific community to navigate and expand the roadmap for the discovery of next-generation therapeutics against these NTDs.
Topics: Humans; Mycobacterium ulcerans; Mycobacterium leprae; Buruli Ulcer; Mycobacterium
PubMed: 38295025
DOI: 10.1021/acsinfecdis.3c00371 -
Frontiers in Medicine 2024
PubMed: 38414623
DOI: 10.3389/fmed.2024.1372149 -
Frontiers in Genetics 2023Leprosy is an infectious disease primarily caused by the obligate intracellular parasite . Although it has been considered eradicated in many countries, leprosy... (Review)
Review
Leprosy is an infectious disease primarily caused by the obligate intracellular parasite . Although it has been considered eradicated in many countries, leprosy continues to be a health issue in developing nations. Besides the social stigma associated with it, individuals affected by leprosy may experience nerve damage leading to physical disabilities if the disease is not properly treated or early diagnosed. Leprosy is recognized as a complex disease wherein socioenvironmental factors, immune response, and host genetics interact to contribute to its development. Recently, a new field of study called epigenetics has emerged, revealing that the immune response and other mechanisms related to infectious diseases can be influenced by noncoding RNAs. This review aims to summarize the significant advancements concerning non-coding RNAs in leprosy, discussing the key perspectives on this novel approach to comprehending the pathophysiology of the disease and identifying molecular markers. In our view, investigations on non-coding RNAs in leprosy hold promise and warrant increased attention from researches in this field.
PubMed: 38116294
DOI: 10.3389/fgene.2023.1295586 -
Nature Communications Sep 2023The cell walls of pathogenic and acidophilic bacteria, such as Mycobacterium tuberculosis and Mycobacterium leprae, contain lipoarabinomannan and arabinogalactan. These...
The cell walls of pathogenic and acidophilic bacteria, such as Mycobacterium tuberculosis and Mycobacterium leprae, contain lipoarabinomannan and arabinogalactan. These components are composed of D-arabinose, the enantiomer of the typical L-arabinose found in plants. The unique glycan structures of mycobacteria contribute to their ability to evade mammalian immune responses. In this study, we identified four enzymes (two GH183 endo-D-arabinanases, GH172 exo-α-D-arabinofuranosidase, and GH116 exo-β-D-arabinofuranosidase) from Microbacterium arabinogalactanolyticum. These enzymes completely degraded the complex D-arabinan core structure of lipoarabinomannan and arabinogalactan in a concerted manner. Furthermore, through biochemical characterization using synthetic substrates and X-ray crystallography, we elucidated the mechanisms of substrate recognition and anomer-retaining hydrolysis for the α- and β-D-arabinofuranosidic bonds in both endo- and exo-mode reactions. The discovery of these D-arabinan-degrading enzymes, along with the understanding of their structural basis for substrate specificity, provides valuable resources for investigating the intricate glycan architecture of mycobacterial cell wall polysaccharides and their contribution to pathogenicity.
Topics: Animals; Female; Humans; Galactans; Lipopolysaccharides; Mycobacterium tuberculosis; Endometriosis; Mammals
PubMed: 37726269
DOI: 10.1038/s41467-023-41431-2 -
Experimental Biology and Medicine... Nov 2023Leprosy is a neglected chronic infectious disease caused by obligate intracellular bacilli, and . Despite multidrug therapy (MDT) success, leprosy accounts for more... (Review)
Review
Leprosy is a neglected chronic infectious disease caused by obligate intracellular bacilli, and . Despite multidrug therapy (MDT) success, leprosy accounts for more than 200,000 new cases yearly. Leprosy diagnosis remains based on the dermato-neurologic examination, but histopathology of skin biopsy and bacilloscopy of intradermal scraping are subsidiary diagnostic tests that require expertise and laboratory infrastructure. This minireview summarizes the state of the art of serologic tests to aid leprosy diagnosis, highlighting enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (POCT) biotechnologies. Also, the impact of the postgenomic era on the description of new recombinantly expressed -specific protein antigens, such as leprosy Infectious Disease Research Institute (IDRI) diagnostic (LID)-1 is summarized. Highly specific and sensitive molecular techniques to detect DNA as the quantitative polymerase chain reaction (qPCR) and the loop-mediated isothermal amplification (LAMP) are briefly reviewed. Serology studies using phenolic glycolipid-I (PGL-I) semi-synthetic antigens, LID-1 fusion antigen, and the single fusion complex natural disaccharide-octyl (NDO)-LID show high sensitivity in multibacillary (MB) patients. However, serology is not applicable to paucibacillary patients, as they have weak humoral response and robust cell-mediated response, requiring tests for cellular biomarkers. Unlike ELISA-based tests, leprosy-specific POCT based on semi-synthetic PGL-I antigens and NDO-LID 1 antigen is easy to perform, cheaper, equipment-free, and can contribute to early diagnosis avoiding permanent incapacities and helping to interrupt transmission. Besides its use to help diagnosis of household contacts or at-risk populations in endemic areas, potential applications of leprosy serology include monitoring MDT efficacy, identification of recent infection, especially in young children, as surrogate markers of disease progression to orient adult chemoprophylaxis and as a predictor of type 2 leprosy reactions. Advances in molecular biology techniques have reduced the complexity and execution time of qPCR confirming its utility to help diagnosis while leprosy-specific LAMP holds promise as an adjunct test to detect DNA.
Topics: Adult; Child; Humans; Child, Preschool; Drug Therapy, Combination; Leprostatic Agents; Antigens, Bacterial; Antibodies, Bacterial; Leprosy; Mycobacterium leprae; Glycolipids; DNA; Communicable Diseases
PubMed: 38059475
DOI: 10.1177/15353702231209422 -
Bulletin of the World Health... Apr 2024The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development...
The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect or infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention.
Topics: Humans; Leprosy; Mycobacterium leprae; Sensitivity and Specificity; Models, Statistical; Early Diagnosis
PubMed: 38562197
DOI: 10.2471/BLT.23.290881