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Literature points out to the acquisitions of gene clusters and pathogenicity islands via horizontal gene transfer. Transformation to pathogenic state maybe due to exchange of DNA fragments between bacteria. Some bacterial species contain strains known as commensal to a host and other strains that exhibit pathogenicity.
#Index math in pbp3 arrays drivers#
The drivers of pathogenicity may not only be virulence factors but also the absence of antivirulence factors in bacterial genomes. The findings of the study suggest the presence of pathogenic gene circuits in which some genes belong exclusively to pathogenic strains whereas others can also be abundant in bacterial strains synergistic or commensal to the host. Virulence genes abundant in pathogenic as well as nonpathogenic strains included those facilitating coding of translocation proteins, apparatus proteins, and chaperons. A recent study involving 50 bacterial genomes found some virulence factors to be exclusive to pathogenic bacterial strains in this small sample. Yet, specificity of virulence factors to certain bacterial and strains is poorly understood. Virulence factors may cause disease in multiple hosts. Nevertheless, not only the VFDB database is valuable for identifying genes linked to pathogenicity in specified bacteria (even strains), but it also serves as a benchmark for studies predicting pathogenicity linked gene clusters.
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Since the metagenome of a human microbiome contains over three million genes, the extent of our knowledge on virulence genes may not be close to saturation. The database presents genes and gene groups (virulence factors) associated with infectious disease. The large research literature on bacterial pathogenicity was recently curated into an open access web platform, the Virulence Factor Database or VFDB. It is clear that pathogenicity is context dependent. Production of enzymes that degrade host cytoskeleton and cause damage is linked to bacterial strain density and quorum sensing. Synthesis of secreted virulence factors are transcriptionally regulated by environmental stimuli. A bacterial strain may appear as asymptotic or pathogenic depending on the state of the immune system of the host, composition of the microbiome, presence and absence of elicitors, and other environmental factors. Pathogenic bacterial strains could be defined as those with capacity to harm the host and cause disease. Microbiology experiments identified a large number of bacterial virulence mechanisms conserved through evolution. Scanning microbiome libraries for these circuitry motifs will provide further insights into the complex and context dependent pathogenicity of bacteria.
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Extensive literature search substantiated a bulk majority of the commensal and pathogenic circuitry in our predicted list. Present study produces for the first time, a signature, in the form of a robust list of gene circuitry whose presence or absence could potentially define the pathogenicity of a microbiome.
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Our study also identified bacterial genera containing a circuit, elements of which were previously linked to Alzheimers disease. Antibiotics-resistant bacterial strains possessed genes modulating phagocytosis, vesicle trafficking, cytoskeletal reorganization, and regulation of the inflammatory response. Pathogen-abundant gene circuits included modules in one-carbon folate, two-component system, type-3 secretion system, and peptidoglycan biosynthesis. Other synergy-linked circuits reduced drug-induced toxicity. Gene circuits relatively abundant in nonpathogenic bacteria often mediated biosynthesis of antibiotics. We projected the resultant lists of ortholog genes onto KEGG bacterial pathways to identify clusters and circuits, which can be linked to either pathogenicity or synergy. In addition, we carried out genome comparison within a genus for the seventeen largest genera in our genome collection. Using data on the gene contents of these genomes, we identified sets of genes highly abundant in pathogenic but relatively absent in commensal strains and vice versa. We used the KEGG repository and extensive literature searches to identify among the 2527 bacterial genomes in the literature those implicated as pathogenic to the host, including those which show pathogenicity in a context dependent manner. Pathogenic potential of bacteria has been shown to be context dependent, varying in response to environment and even within the strains of the same genus. Bacterial infections comprise a global health challenge as the incidences of antibiotic resistance increase.