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Mycobacterium abscessus is a nontuberculous mycobacterium, associated with broncho-pulmonary infections in individuals suffering from cystic fibrosis, bronchiectasis, and pulmonary diseases. The risk factors for transmission include biofilms, contaminated water resources, fomites, and infected individuals. M. abscessus is extensively resistant to antibiotics. To date, there is no vaccine and combination antibiotic therapy is followed. However, drug toxicities, low cure rates, and high cost of treatment make it imperfect. Over the last 20 years, bioinformatic studies on M. abscessus have advanced our understanding of the pathogen. This review integrates knowledge from the analysis of genomes, microbiomes, genomic variations, phylogeny, proteome, transcriptome, secretome, antibiotic resistance, and vaccine design to further our understanding. The utility of genome-based studies in comprehending disease progression, surveillance, tracing transmission routes, and epidemiological outbreaks on a global scale has been highlighted. Furthermore, this review underlined the importance of using computational methodologies for pinpointing factors responsible for pathogen survival and resistance. We reiterate the significance of interdisciplinary research to fight M. abscessus. In a nutshell, the outcome of computational studies can go a long way in creating novel therapeutic avenues to control M. abscessus mediated pulmonary infections. [ABSTRACT FROM AUTHOR]

Mycobacterium avium complex (MAC) houses a group of non-tuberculous mycobacteria causing pulmonary and disseminated infections. They are accountable for nodular bronchiectatic and fibrocavitary lung diseases in humans, Johne’s disease in ruminants, and respiratory diseases in birds. MAC infections pose challenges, owing to antibiotic resistance, prolonged therapy with antibiotic combinations, side effects, and risk of reinfections. Our objective was to summarize the outcome of computational research on the bacteria in MAC. This aimed to advance our understanding of characteristics, pathogenicity, and transmission dynamics to control infections. We incorporated information from the research on genomes, microbiomes, phylogeny, transcriptomes, proteomes, antibiotic resistance, and vaccine/drug target development to enhance our knowledge. It illuminated the significance of computational studies in distinguishing MAC species/subspecies and recognizing: virulence factors, lineage-specific markers, and transmission clusters. Moreover, it assisted in understanding: genomic diversity, resistance patterns, impact of polymorphisms in disease susceptibility, and taxa-induced dysbiosis in microbiomes. Additionally, this work highlighted the outcome of bioinformatic studies in predicting suitable vaccine epitopes, and novel drug targets to combat MAC infections. Bioinformatic research on bacteria within MAC has contributed to a deeper insight into the pathogens. These would facilitate better diagnosis, improved: therapeutic strategies, patient-specific surveillance, and community-level awareness. [ABSTRACT FROM AUTHOR]

The non-tuberculous Mycobacterium kansasii, is the causative agent of destructive pulmonary and extrapulmonary infections in immunocompromised persons. Incessant use of multiple antibiotics and lack of effective vaccines did little to combat M. kansasii mediated infections. Here, a bioinformatic analysis has been carried out using PanExplorer, to analyze the pangenome aimed at functional characterization of the bacterium, understanding it's pathogenic lifestyle and recognize the factors shaping evolution and variations amongst strains. M. kansasii had a large core genome (60.2%), a small (11.9%) dispensable genome and 27.9% strain-specific genes. The core genome of M. kansasii had a high concentration of COGs (Cluster of orthologous genes) linked to energy production and conversion, amino acid transport and metabolism, nucleotide transport and metabolism, coenzyme transport and metabolism, and secondary metabolite biosynthesis, transport and metabolism. Interestingly, numerous genes within the core and dispensable genome were associated with pathogenesis and virulence. Noteworthy among them were type VII secretion, ESX, PP and PPE family proteins. Although, M. kansasii genomes revealed overall relatedness and conservation, genomic rearrangements caused variability within the strains. The information from this analysis could assist future microbial genomics research on M. kansasii, and further studies, e.g., concerning distinctive gene clusters, and evolution. [ABSTRACT FROM AUTHOR]

Mycobacterium ulcerans is a non-tuberculous mycobacterium responsible for causing Buruli ulcer. This is a neglected tropical disease characterized by ulceration, necrotization and scarring of the soft tissues in human limbs. Pathogenesis of M. ulcerans is mediated by a cytotoxic and immunosuppressive compound called mycolactone. This steadily evolving mycobacteria has adapted itself with the aquatic insect ecosystem. Human communities in wetland ecosystems are prone to Buruli ulcer and several endemic regions have been identifi ed. So far, there is no vaccine and surgery or prolonged treatment with antibiotic cocktail has been mandated to overcome resistance patterns. Application of bioinformatics tools in M. ulcerans and Buruli ulcer research during the post genomic era, has provided immense opportunities. In this review, we summarize the outcome of genome studies, comparative genomics, population genomics, genetic diversity analysis, phylogenetic studies and proteomics research pertaining to this disease. We also highlight the implications of in silico vaccine design and computational studies on natural products. Resultant fi ndings are conducive for interpreting genome architecture, pathogenomic evolution and intraspecifi c divergence due to phylogeographic and virulence factors of M. ulcerans. Moreover, the outcome of population genomics studies in disease management, coupled with the efforts in discovering vaccine candidates and novel lead compounds, will enrich our understanding of Buruli ulcer. [ABSTRACT FROM AUTHOR]

Cytochrome P450 monooxygenases (CYPs or P450s) are catalytically versatile hemoproteins, associated with drug metabolism, substrate utilization and pathogenesis. Mycobacterium ulcerans is a human pathogen causing Buruli ulcer. The study intended to investigate frequency and diversity of CYPs from M. ulcerans strains, understand the pan-CYPome clustering patterns and interconnection of CYPs using bioinformatics tools. M. ulcerans strains demonstrated the presence of 261 CYPs categorized into 35 families and 38 subfamilies. CYP138, CYP140, CYP189 and CYP125 were the flourishing families. Around, 20 CYP families and 20 subfamilies were conserved. Flourishing and conserved CYP families/subfamilies were associated with lipid metabolism, substrate utilization etc. CYP140 had a role in pathogenesis. CYP279 was the least dominant family. CYP135, CYP183, CYP190, CYP271 and CYP276 were diagnostic markers for M. ulcerans subsp. shinshuense strain ATCC 33728 and M. ulcerans strain P7741. The pan-CYPome specified that M. ulcerans is evolving by gaining CYPs. CYP centric clustering revealed diversity and resemblances among M. ulcerans strains. More diverse nature of the M. ulcerans strain Harvey could be attributed to its larger size and geographical location. Co-occurrence network demonstrated mutual associations amongst substantial number of CYP families/subfamilies. This work provided comprehensive understanding of previously unexplored CYPs from M. ulcerans. [ABSTRACT FROM AUTHOR]

Members of the genus Xanthomonas are significant phytopathogens, which cause diseases in several economically important crops including rice, canola, tomato, citrus, etc. We have analyzed the genomes of six recently sequenced Xanthomonas strains for their synonymous codon usage patterns for all of protein coding genes and specific genes associated with pathogenesis, and determined the predicted highly expressed (PHX) genes by the use of the codon adaptation index (CAI). Our results show considerable heterogeneity among the genes of these moderately G+C rich genomes. Most of the genes were moderate to highly biased in their codon usage. However, unlike ribosomal protein genes, which were governed by translational selection, those genes associated with pathogenesis (GAP) were affected by mutational pressure and were predicted to have moderate to low expression levels. Only two out of 339 GAP genes were in the PHX category. PHX genes present in clusters of orthologous groups of proteins (COGs) were identified. Genes in the plasmids present in two strains showed moderate to low expression level and only a couple of genes featured in the PHX list. Common genes present in the top-20 PHX gene-list were identified and their possible functions are discussed. Correspondence analysis showed that genes are highly confined to a core in the plot. [ABSTRACT FROM AUTHOR]