ABSTRACT
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Toll-like receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.
ABSTRACT
Aims@#Klebsiella pneumoniae is considered to be one of the most frequent bacterial species associated with urinary tract infections (UTIs) and recurrent UTIs (RUTIs) worldwide. The present study aimed to comprehensively characterize K. pneumoniae isolates from women suffering from UTI and RUTIs. @*Methodology and results@#A total of 15 clinical isolates, collected from different hospitals in Bangladesh, were tested for biochemical features, and amplified by PCR. Antibiogram assay was performed by disk-diffusion assay. Phylogenetic and functional features were analyzed using bioinformatics platform. XLSTAT was used for principal component analysis (PCA). PCR amplification using Klebsiella hemolysin gene (khe) confirmed the presence of K. pneumoniae in agarose gel with expected product size of 486 kb. Antibiogram assay revealed all K. pneumoniae isolates to be completely resistant to six out of ten relevant drugs namely ampicillin, cephradine, chloramphenicol, erythromycin, kanamycin and sulfamethoxazole used for treating UTIs in Bangladesh. Sequencing of 16S rRNA gene of clinically significant K. pneumoniae isolates showed a high level of sequence divergence among the isolates from UTI and RUTIs as well as functional features such as SNP variants and restriction sites. @*Conclusion, significance and impact of study@#We surmise that the results could be used as a pipeline for further research in the identification of K. pneumoniae associated with UTI and RUTIs, and treatment of infection.
ABSTRACT
In this present study, the bark extracts of Averrhoa bilimbi were subjected to the thrombolytic activities were assessed by using human erythrocyte and the results were compared with standard streptokinase (SK). On the other hand, bark extracts of A. bilimbi revealed moderate antibacterial activity against some microorganisms used in the screening. Preliminary phytochemical investigation suggested the presence of flavonoids, saponins and alkaloids.
ABSTRACT
Chitinases (designated as SPCs) were isolated from „Shilbilati‟ potatoes, a potato prototype cultivated in Bangladesh by affinity chromatography on a chitin column. SPCs agglutinated rat erythrocytes at the minimum concentration of 7 μg/mL and showed toxicity against brine shrimp nauplii with the LC50 value of 20 μg/mL. The chitinases also agglutinated seven bacterial strains among the twelve as studied. Pseudomonas aeruginosa, Bacillus subtilis and Salmonella typhi were the most sensitive towards the SPCs and were agglutinated at 1.2, 2.5 and 5.0 μg/mL protein concentrations respectively. Antibacterial tests demonstrated that SPCs showed inhibitory activity against the pathogenic bacteria Staphylococcus aureus, Bacillus subtilis and Salmonella typhi. Antifungal activity was investigated by the disc diffusion method. Five fungal species (Candida albicans, Aspergillus niger, Fusarium vasinfectum, Aspergillus fumigatus and Aspergillus flavus) and two fungal genus (Penicillium and Mucor sp.) were examined in the assay. SPCs showed antifungal activity against Candida albicans, Fusarium vasinfectum and Penicillium sp.