41 research outputs found
Comparison of proline-glutamate-proline-glutamate-polymorphic GC-rich sequences family protein Wag22 (Rv1759c), PE_PGRS31 (Rv1768), PE_PGRS32 (Rv1803), and PE_PGRS33 gene (Rv1818c) in exponential state and under In vitro model of latency in same clinical isolates of Mycobacterium tuberculosis: Frameshift mutation in extensively drug-resistant and totally drug-resistant tuberculosis bacilli
No full textBackground: Proline-glutamate (PE)/proline-PE (PPE) proteins play an important role in the development of mycobacterial pathogenicity by modulating the host immune system. In the present investigation, the structural changes in PE-polymorphic GC-rich sequences (PGRS) family protein Wag22 (Rv1759c), PE_PGRS31 (Rv1768), PE_PGRS32 (Rv1803), and PE_PGRS33 gene (Rv1818c) were compared and analyzed in exponential state and under in vitro model of latency in same clinical isolates of Mycobacterium tuberculosis (MTB). Methods: MTB strains were isolated from clinically and laboratory-confirmed cases of tuberculosis (TB). The TB isolates were subjected to the Xpert MTB/rifampin test and then, further susceptibility testing using proportional methods was performed on them. The isolates were characterized using both 16S–23S RNA and hsp65 genes spacer polymerase chain reaction-restriction fragment length polymorphism. Selected isolates studied at two experimental set–up at exponential phase OD 600 = 0.05 (5 cfu/mL × 106 cfu/mL) and under zero oxygen and nutrition for 26 months to selected isolates studied at two experimental setup in exponential phase OD600 = 0.05 (5 cfu/mL × 106 cfu/mL) and under zero oxygen and nutrition after 26 months. Whole-genome sequencing was performed on studied isolates and the protein structures were analyzed using a bioinformatics web server. Results: No deletion, insertion, or substation occurred in susceptible, mono-drug and multidrug resistant-TB isolates were observed at PE-PGRS family protein Wag22 (Rv1759c) and PE_PGRS31 (Rv1768) at exponential phase. Although, a large deletion (at Rv1759c; Rv1768) was observed in extensively drug-resistant (XDR) and totally drug-resistant (TDR) TB isolates at the exponential phase. All studied TDR-TB isolates had a common deletion position from amino acid 1 (methionine) to amino acid 83 (glycine) and from amino acid 725 (proline) to amino acid 914 (threonine) at PE-PGRS family protein Wag22 (Rv1759c). At PE_PGRS32 (Rv1803), deletion occurred from amino acid 1 (methionine) to amino acid 212 (glycine) in latent TDR-TB bacilli. No changes in Rv1803 were observed in other studied isolates. In contrast, 66.6% of studied isolates had either insertion, deletion, substitution, or combination of changes at PE_PGRS33 (Rv1818c). However, the majority of changes at Rv1818c occurred in drug-resistant isolates. We also documented the region of deletion and insertion at PE_PGRS33 (Rv1818c) is different in active and latent TDR-TB isolates. Conclusions: Changes in these PE-PGRS family protein was associated with drug susceptibility patterns of individual isolates. Our result showed a total frameshift mutation of protein that had a different length in comparison to the original protein. These changes might disturb the interactions between XDR and TDR-TB isolates and immune responses, which needs further investigation
Genotypic distribution of three polymorphisms of IL-10 in patients with PEX, PEXG, and POAG.xlsx
No full textGenotypic distribution of three polymorphisms -592C/A (rs1800872), -819C/T (rs1800871) and -1082A/G (rs1800896) of IL-10 gene promoter in patients with pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG
The importance of single nucleotide polymorphisms in interferon gamma receptor-1 gene in pulmonary patients infected with rapid grower mycobacterium
No full textAbstractObjective/BackgroundInterferon gamma (IFN-γ) plays a key role in protective immune response against Mycobacterial infection. IFN-γ excretes its antimycobacterial effectors mechanisms by activation of macrophages and dendritic cells via interaction with its receptor complex, that is, a ligand-binding subunit [IFN-γ receptor (IFNGR)1] and an accessory subunit (IFNGR2) on the cell surface. It has been shown that individuals with complete or partial IFNGR1 receptor deficiency are highly susceptible to infection by nontuberculous mycobacteria (NTM), Mycobacterium tuberculosis, and some Salmonella species. In the present study, we aimed to study the IFNGR1 T-56C single nucleotide polymorphism (SNP) in pulmonary patients that were infected with rapid grower mycobacterium.MethodsSputum specimens from suspected nontuberculosis pulmonary patients (n=95) were digested and decontaminated using 4% NaOH method. Molecular identification of mycobacterium was then performed by hsp65 genes using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Finally, the host genomic DNA from confirmed patients with rapid-grower mycobacterium (n=20) and control subjects (n=20) were screened for SNPs of IFNGR1 (T-56C) by PCR-RFLP.ResultsOut of 95 NTM patients, 20 (21.0%) were infected with rapid grower mycobacterium (RGM). The frequency of Mycobacterium chelonae (n=12) was more than Mycobacterium fortuitum (n=8), but the differences were not statistically significant. Interestingly, 18 patients (90%) had CC genotypes, whereas the remaining two had TC genotypes. The frequency of CC genotypes in the control group was <10% (p<0.05).ConclusionThere is a significant association between SNP of IFNGR1 at –56 and susceptibility to rapid grower infection
Modified rifampin nanoparticles: Increased solubility with slow release Rate
No full textBackground: Recent advances in nanotechnology-based drug delivery system have been shown to improve either antibacterial efficacy or pharmacokinetics behavior.The aim of this study was to design a rifampin nanoparticle (RIF-NP) which has a high loading capacity with the slow release profile. Material and Methods: The designed chitosan/gelatin/lecithin (Chg/L) RIF-NPs were prepared by multilamellar vesicle. Thereafter, the particle size, zeta potential, morphology, and release rate were investigated. To optimize the loading capacity and release profiles, different concentrations of lecithin were used. Results: Our results showed a correlation of lecithin concentration with size, zeta potential, and loading capacity of RIF-NPs. Increases in lecithin concentration (0.2–2.0 g) could cause a significant size reduction in NPs (250–150 nm); the amount of zeta potential (from 14 to 49 mV;P < 0.05) and loading capacity increases from 8% to 20% (P < 0.05). Designed NPs had slow drug release profile which was influenced by pH and lecithin concentration. The cumulative percentage of RIF released at pH 7.4 was approximately 93% up to 12 h. In overall, release profile was better than standard drug, even in various pH conditions (pH = 1, 3.4, and 7.4). The Chg/L-RIF NPs may be considered as a promising drug nanocarrier. Conclusions: These NPs release RIF in slow and constant rate, which effectively might eliminate the bacilli and prevent the formation of RIF-resistant bacilli
A review on the shape changes in pathogenic bacteria with emphasis on Mycobacterium tuberculosis
No full textBacteria show a plenty of cellular shapes and can alter their forms. The bacterial cell shape is functionally important. Bacteria have a number of options to select their shapes in order to uptake more nutrient, motility, attachment to surface, symmetrical division of chromosomal elements, and localization of complex secretion apparatuses. Some factors including peptidoglycan and cytoskeleton-like proteins can regulate and keep the bacterial shape. In the case of Mycobacterium tuberculosis, the reported morphological variation in the pathogen are classified into two categories; those which frequently seen at exponential phase of growth that is rod, V, Y-shape, branched, or buds, and those that are seen occasionally under stress or environmental conditions which are round, oval, ultra-virus, spore-like, and cell wall defiant or L-forms. Growth conditions and age of the cells can influence on the shape and size of the pathogen in a range from coccobacilli to long rods. Under unsuitable conditions including starvation or oxygen deprivation, tubercle bacillus assumed a swollen shape without making the vacuolar or globoid bodies. The physical circumstances and nutritional feature will control the temporary lifestyle of the pathogen
Adaptive Mechanisms of Mycobacterium tuberculosis: Role of fbiC Mutations in Dormancy and Survival
No full textThis review examines the impact of F420 biosynthesis protein C (fbiC) mutations in Mycobacterium tuberculosis (Mtb) and their influence on the bacterium’s dormancy mechanisms. The potential role of fbiC mutations and functional impairments in the persistence of Mtb is emphasized. Tuberculosis (TB) bacilli can enter a dormant state with minimal metabolic activity, allowing them to conserve resources and survive in low-nutrient, low-oxygen environments for extended periods. While the fbiC gene contributes to dormancy, Mtb can achieve this state through multiple genetic and metabolic pathways, suggesting that it may still undergo dormancy even with functional impairments in fbiC. In this review, we utilized several scientific databases, including PubMed, Web of Science, and Google Scholar, and set of key search terms including “fbiC gene,” “F420 Biosynthesis,” “Mycobacterium tuberculosis,” “Dormancy,” and “Drug Resistance” to highlight the significance of the fbiC gene in regulating dormancy and explore how Mtb compensates for fbiC dysfunction through various metabolic adaptations
Epidemiological Distribution of Nontuberculous Mycobacteria Using Geographical Information System
No full textThe association between computed tomography scan findings of pulmonary infection caused by atypical mycobacteria and bacillus count in sputum samples
No full textBackground: The use of imaging techniques is important for prompt diagnosis and treatment of atypical mycobacterial infections; it also reduces the burden of these infections. The purpose of the present study was to determine the association between computed tomography (CT) scan findings of pulmonary infection caused by atypical mycobacteria and bacillus count in sputum samples. Methods: This cross-sectional, observational, comparative study included 50 consecutive patients with pulmonary infection caused by atypical mycobacteria, who were hospitalized in Masih-Daneshvari Hospital of Tehran, Iran during 2012–2017. The association between CT scan findings of pulmonary infection caused by atypical mycobacteria and bacillus count in sputum samples was determined in these patients. Results: The results demonstrated that the presence of nodules smaller than 5 mm in diameter, consolidation, bronchiectasis, and pleural thickening were related to bacillus count in sputum samples (P < 0.05). Conclusion: Some CT scan findings, such as nodule diameter smaller than 5 mm, consolidation, bronchiectasis, and pleural thickening, may be indicators of atypical mycobacterial infection. Increased number of involved lobes with bronchiectasis can promote early diagnosis in patients with higher smear and culture grading
A review on the C-terminal domain of channel protein with necrosis-inducing toxin as a novel necrotizing toxin of Mycobacterium tuberculosis
No full textComputed Tomography Findings of Pulmonary Mycobacterium simiae Infection
No full textNontuberculous mycobacterial (NTM) pulmonary infections can be quite similar to tuberculosis, both clinically and radiologically. However, the treatment protocol is not similar. Mycobacterium simiae is a rare cause of NTM pulmonary infection. Herein, we aimed to evaluate and compare the computed tomography (CT) scan findings of M. simiae infection in lungs. For this reason, thirty-four patients (n=34) with M. simiae lung infection were retrospectively evaluated. Diagnosis was confirmed by American Thoracic Society (ATS) guidelines and CT scans were reviewed in both lung and mediastinal windows. The average age of patients was 63±14.54 years and 52.9% were male. The majority of patients had cough (91.2%) and sputum production (76.5%). Clinically, 41.2% of patients had previous history of TB (14/34), 38.2% had cardiac diseases (13/34), and 35.3% had diabetes mellitus (12/34). The most common CT findings in our study were nodular lesions (100%) and bronchiectasis (85.29%). Regarding the severity, grade I bronchiectasis was the most prevalent. Other prominent findings were tree-in-bud sign (88.2%), consolidation (52.94%), and lobar fibrosis and volume loss (67.6%). There was no significant zonal distribution of findings. In conclusion, nodular lesions and bronchiectasis are the most frequent features in CT scan of M. simiae pulmonary infection
