Mycobacterial disease

The MYC-Associated Zinc Finger Protein (MAZ) plays important roles in chromatin organization and gene transcription regulation. Dysregulated expression of MAZ causes diseases, such as glioblastoma, breast cancer, prostate cancer, and liposarcoma. Previously, it has been reported that MAZ controls the proinflammatory response in colitis and colon cancer via STAT3 signaling, suggesting that MAZ is involved in regulating immunity-related pathways. However, the molecular mechanism underlying this regulation remains elusive...

Despite major global efforts to eliminate tuberculosis, which is caused by Mycobacterium tuberculosis (Mtb), this disease remains as a major plague of humanity. Several factors associated with the host and Mtb interaction favor the infection establishment and/or determine disease progression. The Early Secreted Antigenic Target 6 kDa (ESAT-6) is one of the most important and well-studied mycobacterial virulence factors. This molecule has been described to play an important role in the development of tuberculosis-associated pathology by subverting crucial components of the host immune responses...

BACKGROUND: Mycobacterium avium complex (MAC), including Mycobacterium intracellulare is a member of slow-growing mycobacteria and contributes to a substantial proportion of nontuberculous mycobacterial lung disease in humans affecting immunocompromised and elderly populations. Adaptation of pathogens in hostile environments is crucial in establishing infection and persistence within the host. However, the sophisticated cellular and molecular mechanisms of stress response in M. intracellulare still need to be fully explored...

UNLABELLED: The timely identification of microbial pathogens is essential to guide targeted antimicrobial therapy and ultimately, successful treatment of an infection. However, the yield of standard microbiology testing (SMT) is directly related to the duration of antecedent antimicrobial therapy as SMT culture methods are dependent on the recovery of viable organisms, the fastidious nature of certain pathogens, and other pre-analytic factors. In the last decade, metagenomic next-generation sequencing (mNGS) has been successfully utilized as a diagnostic tool for various applications within the clinical laboratory...

Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for non-muscle invasive bladder cancer (NMIBC), administered after its transurethral resection. Although its instillation is generally well tolerated, BCG-related infectious complications may occur in up to 5% of patients. Clinical manifestations may arise in conjunction with initial BCG instillation or develop months or years after the last BCG instillation. The range of presentations and potential severity pose an imminent challenge for clinicians...

Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen's cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen's cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids from Mycobacterium smegmatis , and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria...

Peptidoglycan synthesis is an underutilized drug target in Mycobacterium tuberculosis ( Mtb ). Diazabicyclooctanes (DBOs) are a class of broad-spectrum β-lactamase inhibitors that also inhibit certain peptidoglycan transpeptidases that are important in mycobacterial cell wall synthesis. We evaluated the DBO durlobactam as an inhibitor of BlaC, the Mtb β-lactamase, and multiple Mtb peptidoglycan transpeptidases (PonA1, LdtMt1 , LdtMt2 , LdtMt3 , and LdtMt5 ). Timed electrospray ionization mass spectrometry (ESI-MS) captured acyl-enzyme complexes with BlaC and all transpeptidases except LdtMt5 ...

BACKGROUND: World Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India...

BACKGROUND: The increasing number of patients with miliary tuberculosis (MTB) is a concern in an aging society because of its high mortality rate. Several prognostic biomarkers for MTB have been identified; however, the predictive ability of monocytes as biomarkers remains unknown. This study demonstrates the usefulness of monocytes as prognostic biomarkers for MTB. MATERIALS AND METHODS: We retrospectively compared the clinical findings of 52 patients with MTB hospitalized between April 2013 and October 2021...

Mycobacterium Tuberculosis (Mtb) causing Tuberculosis (TB) is a widespread disease infecting millions of people worldwide. Additionally, emergence of drug resistant tuberculosis is a major challenge and concern in high TB burden countries. Most of the drug resistance in mycobacteria is attributed to developing acquired resistance due to spontaneous mutations or intrinsic resistance mechanisms. In this review, we emphasize on the role of bacterial cell cycle synchronization as one of the intrinsic mechanisms used by the bacteria to cope with stress response and perhaps involved in evolution of its drug resistance...

BACKGROUND: Xpert MTB/RIF Ultra (Ultra) is an automated molecular test for the detection of Mycobacterium tuberculosis in sputum. We compared the sensitivity of Ultra to that of mycobacterial growth indicator tube (MGIT) liquid culture, considered the most sensitive assay in routine clinical use. METHODS: In this prospective, multicentre, cross-sectional diagnostic accuracy study, we used a non-inferiority design to assess whether the sensitivity of a single Ultra test was non-inferior to that of a single liquid culture for detection of M tuberculosis in sputum...

BACKGROUND: Although international nontuberculous mycobacterial pulmonary disease (NTM-PD) guidelines highlight symptom presence at diagnosis, the clinical characteristics of asymptomatic Mycobacterium avium complex pulmonary infection (MAC-PI) patients remain understudied. We clarified the clinical characteristics and course of asymptomatic MAC-PI patients. METHODS: We retrospectively analyzed 200 consecutive patients with MAC-PIs and adequate available data who newly met the microbiological and radiological criteria for NTM-PD at Fukujuji Hospital from January 2018 to June 2020...

Canine mycobacterial disease was first recognised over 100 years ago but is now an emerging concern. All reported cases of tuberculous disease in dogs have been caused by infection with one of three Mycobacterium tuberculosis-complex (MTBC) organisms (M. tuberculosis, Mycobacterium bovis, and Mycobacterium microti). Molecular PCR and interferon-gamma release assays offer alternative or complementary diagnostic pathways to that of specialist culture, which is limited by availability, sensitivity, and the time it takes to get a result...

Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 µg/mL to live cultures of Mycobacterium tuberculosis, M. avium , M. bovis , M. fortuitum , M. intracellulare , and M. smegmatis American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multi-drug resistant, and extensively drug resistant M...

Here, we reported the diagnosis and treatment of a case of HIV infected person complicated by an extremely rare infection with Mycobacterium celatum . Due to the similarity of homologous sequence regions between Mycobacterium celatum and Mycobacterium tuberculosis complex, the identification of conventional Mycobacterium species was incorrect, which was corrected after first-generation 16S rRNA sequencing. This report aimed to improve the clinical understanding of Mycobacterium celatum infection and the level of differential diagnosis between non-tuberculous mycobacterial disease and tuberculosis...

Nontuberculous mycobacteria associated intracranial infection is a rare disease that mainly occurs in HIV-infected patients. The disease has a poor prognosis. The authors report a case of non-tuberculous mycobacterial meningoencephalitis in a non-AIDS patient, but long history of poorly controlled type 2 diabetes mellitus. A 55-year-old, right-handed, male patient presented with an 8-day history of fever, episodes of severe headache with signs of meningeal irritation. MRI showed hyperintensities/contrast enhancement in the visual pathways, basal ganglia sellar region and leptomeninges...

Background Tuberculosis (TB) remains a global health concern, with India bearing a substantial burden. Paediatric TB, especially extrapulmonary TB (EPTB), presents unique diagnostic challenges due to its paucibacillary nature and the difficulty in obtaining suitable samples in children. Accurate and timely diagnosis is crucial to initiate appropriate treatment and mitigate disease spread. The MPT64 antigen test has shown promise in diagnosing TB, but its performance in paediatric EPTB remains underexplored...

Mycobacterium porcinum  is a nontuberculous mycobacteria (NTM) recently identified to cause human infection. Correct speciation of NTMs can be difficult and result in misdiagnosis and delayed treatment. Because of the paucity of the literature, there is a lack of awareness of the possibility of serious infections caused by  M. porcinum . Although severe infections tend to occur in individuals with certain risk factors, the primary being an immunocompromised state, our case illustrates that it can also be possible in non-severely immunocompromised individuals...

RATIONALE: Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), there are geographical variations in clinical characteristics. We investigated the clinical characteristics of patients with NTM-PD in South Korea. METHODS: We systematically reviewed articles about patients with NTM-PD in South Korea until February 2022. Individual participant data, regardless of treatment, were collected using a standard case report form. RESULTS: The data of 6,489 patients from 11 hospitals between 2002 and 2019 were analyzed...

People who have structural or developmental lung disease are more likely to develop non-tuberculous mycobacterial infections. We present the case of a young man in his 30s who had unilateral pulmonary artery agenesis on the right side and presented with a 6-month history of productive cough and fever. His CT scan showed nodular and cavitating lesions on the right side, and sputum analysis confirmed infection with Mycobacterium chimaera He had to undergo modifications in his treatment, including a change from rifampicin to rifabutin due to drug interactions and his amikacin had to be stopped due to signs of vestibular toxicity...