Search Results (215)

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection primarily caused by Mycobacterium avium complex (MAC) and Mycobacterium abscessus. These species differ markedly in antibiotic susceptibility and treatment response, yet the contribution of the respiratory microbiome to this clinical variability remains unclear. To date, however, comparative analyses of microbiome differences between MAC-PD and M. abscessus-PD and their associations with disease severity are limited. Methods: We conducted microbiome analysis of sputum from 37 patients with NTM-PD. Patients were antibiotic-naïve and classified into MAC-PD (n = 29) and M. abscessus-PD (n = 8) groups. Disease severity was determined using radiologic extent on chest computed tomography. Bacterial communities were profiled by 16S rRNA gene sequencing, and differential taxa and predicted functional pathways were analyzed using LEfSe and KEGG orthology databases. Results: Distinct microbiome profiles were observed between MAC-PD and M. abscessus-PD. Three anaerobic species—Porphyromonas pasteri, Fusobacterium periodonticum, and Prevotella nanceiensis—were significantly enriched in M. abscessus-PD (LDA effect size > 3, p < 0.05). Functional biomarker analysis revealed significant enrichment of the cobalamin (vitamin B12) biosynthesis pathway in patients with severe disease, while the C19/C18 steroid hormone biosynthesis pathway was enriched in those with mild disease (p < 0.05). Conclusions: In conclusion, our study demonstrates distinct differences in the respiratory microbiome between MAC-PD and M. abscessus-PD and identifies specific functional pathways associated with disease severity in NTM-PD. These findings highlight the potential value of microbial metabolic signatures as biomarkers for disease assessment. Full article

Background: Infection with Mycobacterium avium paratuberculosis (MAP) is closely associated with Crohn’s disease (CD) development, where excessive inflammation and marked intestinal damage are observed. Objectives: In this study, the role of short chain fatty acids, including propionic acid (PPA) and butyric acid (BA), was evaluated in an in vitro model, mimicking CD characteristics. Methods: MAP-infected THP-1 macrophages were treated with 1 mM and 10 mM of PPA or BA, and the conditioned media was co-cultured in Caco-2 cells. Results: Both PPA and BA caused an M2 shift with significant downregulation (p-value < 0.0001) in pro-inflammatory markers at both the RNA and protein levels. The downregulation is most likely due to the antimicrobial properties of PPA and BA. MAP growth was inhibited by several folds in MGIT (Mycobacteria Growth Indicator Tube) culture media supplemented with PPA or BA. Dysfunctional Caco-2 intestinal epithelial cells’ integrity and function, due to MAP infection, were restored with PPA and BA treatment. Specifically, NOX1 expression was significantly decreased in 10 mM of PPA or BA-treated cells (p < 0.001), as validated by RT-PCR and microscopy. PPA and BA restored tight junction integrity by decreasing Claudin-2 expression in the MAP group. Conclusions: The data clearly demonstrated that short chain fatty acids contain anti-inflammatory and antimicrobial properties with downstream beneficial effects on damaged intestinal epithelial cells, suggesting potential benefits as a dietary supplement for CD patients, particularly those who are not pregnant, due to a possible increased risk of autism spectrum disorder (ASD) development in offspring associated with propionic acid exposure. Full article

The emergence of drug resistance remains a major challenge in the treatment of tuberculosis and other mycobacterial infections. To combat the rise in resistance, strategies that reduce the frequency of resistance mutations are urgently needed. Verapamil is a small-molecule compound that can enhance the potency of companion drugs in combination regimen. Here, we investigate if verapamil can decrease the resistance frequency of antimycobacterial drugs. The results show that verapamil significantly reduces the resistance frequency of multiple antimycobacterial agents, including the DNA gyrase inhibitor moxifloxacin, the protein synthesis inhibitor streptomycin, and the RNA polymerase inhibitor rifampicin in Mycobacterium smegmatis. The presence of point mutations in the target was confirmed for moxifloxacin-resistant M. smegmatis. Suppression of resistance evolution against moxifloxacin by verapamil was also found in the slow-growing, pathogenic mycobacteria M. avium and M. tuberculosis. Real-time qPCR analysis in M. smegmatis showed that verapamil treatment downregulates the expression of multiple efflux pump genes and upregulates DNA repair genes. These findings suggest that verapamil exerts a dual role by interfering with efflux pump functionality and by reducing the probability of chromosomal mutations. The combination of these properties may underlie the promise of verapamil as adjuvant to enhance the effectiveness of current antimycobacterial chemotherapy. Full article

Carotenoid pigments are widely distributed in nature and play a crucial role in protecting organisms from photodynamic damage. However, the characterization of carotenoid production in clinically relevant mycobacteria has been limited due to the low sensitivity of conventional detection methods. We present a descriptive analysis of carotenoid production in seven mycobacterial isolates from the scotochromogenic, photochromogenic, and non-chromogenic groups. To achieve this, we used a combination of High-performance liquid chromatography with diode-array detection (HPLC-DAD) and Ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS) to detect carotenoids pigments. Mycobacterium tuberculosis (MTB) and Mycobacterium bovis (MB) (non-chromogenic mycobacteria) produced β-carotene when cultured in the absence of light, at levels comparable to those of photochromogenic mycobacteria such as M. marinum (MM) and M. kansasii (MK). The highest levels of carotenoids were found in scotochromogenic species M. avium (MAV) and M. gordonae (MGOR). Conversely, M. abscessus (MABS), a non-chromogenic species in which no β-carotene was detected, served as a negative control for matrix effects. As expected, the use of highly sensitive analytical techniques such as HPLC-DAD and UHPLC-MS significantly enhanced the detection of β-carotene compared to visual pigment assessment. These methods allowed the detection of basal β-carotene levels even in mycobacteria classified as non-chromogenic. The proposed analytical approach provides a robust research tool to understand the effects of different stimulus that may alter the cell physiology in terms of pigment production. Full article

Paratuberculosis (Johne’s disease) is a chronic enteric infection of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), leading to significant economic losses in livestock production. While the solute carrier family 11 member 1 (SLC11A1) gene has been implicated in resistance to intracellular pathogens in several species, its role in ovine paratuberculosis remains largely uncharacterized. The present study investigated whether polymorphic variation in the SLC11A1 3′ untranslated region (3′UTR) (GT)_n microsatellite is associated with resistance or susceptibility to MAP infection in sheep. A total of 138 sheep from three breeds (Karagouniki, Boutsika, and Chios) were genotyped. Gene expression analysis was subsequently performed on a subset of 53 animals, which comprised rigorously phenotyped MAP-resistant (n = 18) and MAP-sensitive (n = 35) individuals from the Karagouniki breed. Four predominant alleles, (GT)₂₁, (GT)₂₂, (GT)₂₃, and (GT)₂₄, were identified. The (GT)₂₁ and (GT)₂₃ alleles were significantly enriched among resistant sheep, while (GT)₂₂ and (GT)₂₄ were more frequent in sensitive animals (χ² = 12.4, p = 0.006; Cramér’s V = 0.38). No significant differences in basal SLC11A1 mRNA expression were detected between phenotypic groups. These findings extend previous GWAS results in sheep by providing the first allele-level evidence linking SLC11A1 3′UTR microsatellite polymorphisms to paratuberculosis resistance in sheep. Although limited by sample size and single-breed representation, the results offer a foundation for future functional and genomic selection studies aimed at enhancing disease resilience in small ruminants. Full article

Nontuberculous mycobacteria (NTM) represent a heterogeneous group of environmental opportunistic pathogens that have emerged particularly in immunocompromised individuals and patients with underlying pulmonary disorders. NTM infections primarily affect the lungs, but can also manifest as lymphadenitis, skin and soft tissue infections, and disseminated disease. This retrospective study took into consideration 425 NTM-positive samples collected between May 2011 and December 2023, analyzed by sample type, sex, and age group (0–17, 18–49, 50–65, >65 years). Antimicrobial susceptibility analysis was performed on the 223 NTM strains with greater pathogenic power and most frequently isolated, from 2016 to 2023. Pulmonary NTM disease (NTM-PD) infections were most prevalent in patients over 65 years (52.1%), while extrapulmonary NTM disease (NTM-EPD) occurred most frequently in the 0–17 age group (56.4%). Women were slightly more affected (54.4%) than men (45.6%), with the highest incidence in female individuals over 65 years old. The most frequently isolated NTM species was the Mycobacterium avium complex (MAC) (47% of isolates). Antimicrobial susceptibility testing of 223 isolates from 2016 to 2023 revealed species-specific resistance patterns, with high susceptibility to clarithromycin in MAC (94.7%) and Mycobacterium chelonae (100%), but notable resistance in Mycobacterium abscessus complex (MABC). The increasing incidence of NTM infections underscores the need for improved diagnostic techniques and targeted treatment strategies. Full article

Mycobacterium avium is an opportunistic pathogen and a leading contributor to nontuberculous mycobacterial infections in immunocompromised individuals. However, treatment duration, antibiotic toxicity, and resistance present challenges in the management of mycobacterium infections, prompting the need for novel treatment. N-acetylcysteine (NAC) has demonstrated potent antimycobacterial activity, while antimicrobial peptides such as the cyclic [R₄W₄] have shown additive effects when combined with first-line antibiotics. This study aimed to investigate the mechanism and efficacy of NAC and [R₄W₄] combination therapy against M. avium. A membrane depolarization assay was used to evaluate the effects of NAC and [R₄W₄] on M. avium cell membrane integrity. Antimycobacterial activity was assessed by treating cultures with varying concentrations of NAC, [R₄W₄], a combination, or a sham treatment. The same regimens were applied to M. avium-infected THP-1-derived macrophages to assess intracellular efficacy. NAC and [R₄W₄] each disrupted the M. avium membrane potential, with enhanced effects in combination. The combination treatment significantly reduced M. avium survival in both the culture and infected macrophages compared with NAC alone and untreated controls. [R₄W₄] and NAC also demonstrated potent antibacterial activity, while the lowest MIC and the combination of [R₄W₄] and NAC displayed additive effects, indicating an improved bacterial inhibition compared to individual treatments. These findings demonstrate the additive activity of NAC and [R₄W₄] against M. avium in vitro and suggest that combining antioxidant compounds with antimicrobial peptides may represent a promising strategy for treating mycobacterial infections. Full article

For drug-susceptible TB, the WHO-endorsed first-line regimen (isoniazid, rifampicin, ethambutol, pyrazinamide) remains the global reference. Therapy must always be tailored to drug susceptibility, especially in MDR- and XDR-TB. HIV-associated mycobacterial infections—including Mycobacterium tuberculosis (TB), disseminated Mycobacterium avium complex (MAC), and Mycobacterium leprae (M. leprae)—remain leading causes of morbidity and mortality in people living with HIV (PLWH). TB continues to account for the highest burden of AIDS-related deaths worldwide, while MAC and leprosy complicate care in advanced immunosuppression. This review synthesizes current evidence on epidemiology, clinical features, and management challenges of HIV–mycobacterial co-infections. We discuss drug-susceptible and drug-resistant TB therapies, drug–drug interactions with antiretroviral therapy (ART), and the clinical impact of immune reconstitution inflammatory syndrome (IRIS). Beyond established regimens, we highlight host-directed strategies such as metformin, glutathione augmentation, mTOR modulation, and vitamin D; immunotherapies including interferon-γ, GM-CSF, and IL-7; and therapeutic vaccines (M72/AS01E, MTBVAC, VPM1002) as promising adjuncts. Distinct from guideline-focused overviews, this review emphasizes non-tuberculous mycobacterial disease (NTM, including MAC) and leprosy in PLWH and synthesizes host-directed and adjunctive strategies with their translational prospects, including ART compatibility and IRIS. By integrating TB, NTM, and leprosy across the HIV care continuum, we highlight opportunities not treated in detail elsewhere—particularly HDT-enabled approaches and implementation considerations in PLWH. Full article

Mycobacterium avium complex (MAC) infections present significant therapeutic challenges due to their inherent antibiotic resistance, demanding innovative treatment approaches. This study investigated the antimicrobial and antioxidant potential of a novel compound, Fullerene Gallium Phosphonate (FGP), and compared its effects against a previously tested similar compound, Fullerene Disodium Phosphonate (FDSP). Results of experiments using MAC cultures and infected THP-1 macrophages treated with varying FGP and FDSP concentrations (1, 10, 100 µg/mL) revealed that FGP demonstrated greater efficacy than FDSP in reducing M. avium colony-forming units (CFU), achieving a nearly 3-fold reduction by day 8, compared to a 2-fold decrease with FDSP. In infected macrophages, FGP significantly decreased bacterial load at 1 and 10 µg/mL (p < 0.01). FGP also lowered oxidative stress, reflected by a significant reduction in malondialdehyde (MDA) levels on day 4 (p < 0.05) and decreased IL-6 (2-fold) and TNF-α levels (3-fold) by day 8, indicating both antimicrobial and anti-inflammatory effects. However, FGP paradoxically increased MAC burden at its highest concentration and showed no significant difference in efficacy of different concentrations. These findings suggest that FGP may serve as a promising candidate for antimycobacterial therapy with dual antibacterial and antioxidant effects. Further research is crucial to fully elucidate its mechanism of action and find the optimal therapeutic window. Full article

Nontuberculous mycobacteria are opportunistic pathogens increasingly associated with human disease. Within this group, the Mycobacterium avium complex (MAC), which includes M. avium, M. intracellulare and M. intracellulare subsp. chimaera, is the most frequent cause of infection. The increase in MAC cases worldwide has made it crucial to understand their population structure, clinical relevance and resistance mechanisms. Recent advances in whole-genome sequencing (WGS) and molecular approaches have improved the knowledge of taxonomy, population structure and genetic diversity, while also enabling the investigation of transmission and epidemiology. Clinically, MAC most often causes chronic pulmonary disease, but extrapulmonary forms, including disseminated disease, also occur. Presentation can vary by infecting species, while host factors such as pre-existing lung disease or immunosuppression further increase the risk. Treatment outcomes remain less favourable than desired, in part due to antimicrobial resistance involving de novo-acquired mutations. Pathogenesis is also influenced by interactions between MAC and host cells, including mechanisms of immune evasion and inflammatory modulation. In addition, emerging evidence suggests that gut–lung axis dysbiosis may influence susceptibility to MAC infection. This review outlines current knowledge on the population structure, clinical significance, resistance and host–pathogen interactions of MAC. Full article

Background: Nontuberculous mycobacteria (NTM) are opportunistic pathogens responsible for chronic pulmonary infections, primarily affecting individuals with underlying conditions such as cystic fibrosis (CF). The aim of this review is to present the epidemiological profile of NTM in CF patients, with a focus on incidence, prevalence, predominant species, and geographic distribution. Methods: The search included cross-sectional, retrospective, and prospective observational studies published in English that reported epidemiological data concerning the isolation and/or infection of individuals with CF by NTM. NTM infection was defined as the isolation of any NTM species at least once per patient. Out of an initial 1120 references identified in PubMed, and following the application of exclusion criteria based on PRISMA guidelines, a total of 78 studies were included. Results: The reported prevalence of NTM in CF patients ranges globally from 0% to 40.9%. This wide variability is attributed to population heterogeneity, study period, and geographical region. Of the studies included, 30 were conducted in Europe and 25 in the U.S.A. Mycobacterium abscessus and the Mycobacterium avium complex (MAC) were the most commonly isolated species, with MAC being more prevalent in older individuals. The incidence of NTM pulmonary disease was high, with the majority of cases being associated with M. abscessus. Although emerging evidence suggests that CFTR modulator therapy may reduce the risk of NTM isolation and/or disease, current data remain limited. Conclusions: Nontuberculous mycobacteria are significant pathogens in patients with cystic fibrosis, with a negative impact on respiratory health. Full article

About a quarter of the world’s population is infected with Mycobacterium tuberculosis. Growing antibiotic resistance by this microorganism is a major problem in the therapy of the disease. M. avium-M. intracellulare that emerged as a major opportunistic infection of HIV/AIDS continues to afflict immunocompromised individuals. We describe the use of liposome-encapsulated antibiotics in the experimental and clinical therapy of mycobacterial infections, as well as recent experimental liposomal vaccines against tuberculosis. Liposome-mediated intravenous or inhalational delivery of antibiotics enhances the antibacterial effects of the drugs, particularly for infections of resident macrophages, where the liposomes are passively targeted. Despite experimental successes of liposomal antibiotics in the treatment of mycobacterial and other bacterial infections, applications of this method to the clinic have been lagging. This review underscores the significance of liposomes in the treatment of mycobacterial infections, encompassing their synthesis methods, limitations, and both preclinical and clinical studies, providing guidance for the development of future therapeutic approaches and innovative antimicrobial strategies. Full article

Background/Objectives: Mycobacterium avium, a member of Mycobacterium avium complex (MAC), is an emerging opportunistic pathogen causing MAC-pulmonary disease (PD). Fluoroquinolones (FQs), along with ethambutol (EMB) and rifampicin, are recommended for macrolide-resistant MAC-PD; however, FQ-resistant M. avium have been reported worldwide. WQ-3810 is an FQ with high potency against FQ-resistant pathogens; however, its activity against M. avium has not yet been studied. Methods: In this study, we conducted a DNA supercoiling inhibitory assay to evaluate the inhibitory effect of WQ-3810 on recombinant wild-type (WT) and four mutant DNA gyrases of M. avium and compared the IC₅₀s of WQ-3810 with those of ciprofloxacin (CIP), levofloxacin (LVX), and moxifloxacin (MXF). In addition, we examined WQ-3810’s antimicrobial activity against 11 M. avium clinical isolates, including FQ-resistant isolates, with that of other FQs. Furthermore, we assessed the synergistic action of WQ-3810 with the combination of either EMB or isoniazid (INH). Results: In a DNA supercoiling inhibitory assay, WQ-3810 showed 1.8 to 13.7-fold higher efficacy than LVX and CIP. In the MIC assay, WQ-3810 showed 4 to 8-fold, 2 to 16-fold, and 2 to 4-fold higher antimicrobial activity against FQ-resistant isolates than CIP, LVX, and MXF, respectively. The combination of WQ-3810 and INH exhibited a synergistic relationship. Conclusions: The overall characteristics of WQ-3810 demonstrated greater effectiveness than three other FQs, suggesting that it is a promising option for treating FQ-resistant M. avium infections. Full article

Background: The accumulation of agri-food waste is a major environmental and economic challenge and converting these by-products into bioactive compounds fits within the circular bioeconomy. This study aimed to evaluate the antimicrobial potential of extracts derived from Cannabis sativa L. leaves (CSE), Crocus sativus tepals (CST), and Prunus avium L. cherry waste (VCE) against four key bacterial species (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa). Methods: Minimum inhibitory concentration (MIC) assays were performed to assess antibacterial activity, while a bioinformatic pipeline was implemented to explore possible molecular targets. Full-proteome multiple sequence alignments across the bacterial strains were used to identify conserved, strain-specific proteins, and molecular docking simulations were applied to predict binding interactions between the most abundant compounds in the extracts and their targets. Results: CSE and CST demonstrated bacteriostatic activity against S. aureus and B. subtilis (MIC = 15.6 mg/mL), while VCE showed selective activity against B. subtilis (MIC = 31.5 mg/mL). CodY was identified as a putative molecular target for CSE and CST, and ChaA for VCE. Docking results supported the possibility of spontaneous binding between abundant extract constituents and the predicted targets, with high binding affinities triggering a strong interaction network with target sensing residues. Conclusions: This study demonstrates the antimicrobial activity of these agri-food wastes and introduces a comprehensive in vitro and in silico workflow to support the bioactivity of these agri-food wastes and repurpose them for innovative, eco-sustainable applications in the biotechnology field and beyond. Full article

Sweet cherry (Prunus avium L.), as a high-economic-value fruit with both nutritional and health functions, faces severely constrained plant growth due to underdeveloped root systems and suboptimal orchard site conditions. Plant growth-promoting rhizobacteria (PGPR) demonstrate application potential in regulating plant development and improving soil structure through the release of volatile organic compounds (VOCs). This study systematically evaluated the effects of VOCs from three PGPR strains—Pantoea ananatis D1-28, Burkholderia sp. D4-24, and Burkholderia territorii D4-36—on cherry root development and rhizosphere microbial communities. The results indicate that when D1-28 and D4-24 strains were at 10³ cfu·mL⁻¹ and D4-36 was at 10⁵ CFU·mL⁻¹, their VOCs exhibited optimal growth-promoting effects. Compared with the control group, significant improvements were observed in cherry seedling parameters, including plant height, total biomass, root length, root surface area, and root volume. The VOCs from these strains synergistically promoted plant growth by regulating auxin synthesis pathways in cherry roots while enhancing the relative abundance of beneficial rhizosphere microorganisms. This study establishes the strain-concentration–effect relationship, providing a theoretical foundation to optimize soil microbial environments and promote cherry root development using PGPR. Full article