The Bacterial Guide to Designing a Diversified Gene Portfolio

Beyond the pan-genome: current perspectives on the functional and practical outcomes of the distributed genome hypothesis

“…This results in changing the genotype and phenotype of the cell which may provide a selective advantage in a stressful environment. Multiple transfers distributed around the chromosome may occur during a single competence event [20,7,[46][47][48]. Competence, the metabolic state of being able to take up foreign DNA from the environment into the cell, is triggered by nutrient limitation or other stress conditions as part of the bacterial cell's SOS response.…”

“…Thus, it follows in the case of pathogens that each strain has a unique set of heritable traits with regard to antigen presentation to the host; virulence, including antibiotic resistances and serum resistances; and tissue tropisms, all which contribute to a strain's pathogenicity affecting its ability to colonize, persist in the face of antimicrobial therapy, invade cells and tissues, metastasize to distant sites via systemic spread, and evade or disarms various aspects of the host's innate and adaptive immune systems [1,7,64]. Based on the DGH we developed a comparative and functional genomics program that has provided the data establishing the veracity of the postulate that the genetic determinants of virulence and antibiotic resistance are unique to each strain for multiple pathogenic bacterial species (reviewed in [48]). These include: the Gram-negative pathogens, H. influenzae [14,19,62,65,[70][71][72][73], M. catarrhalis [30,31], P. aeruginosa [12,27,28], and Burkholderia cenocepacia [68]; and the Gram-positive pathogens S. pneumoniae [19][20]29,[74][75][76][77], S. aureus [19], and Gardnerella vaginalis [16].…”

“…Thus, in addition to the set of core genes, each strain has its own unique set of noncore genes from the supragenome [ 1 , 9 , 63 ]. The core genome consists of ‘essential’ genes responsible for the basic aspects of a species’ metabolism and major phenotypic traits [ 13 , 15 ], including genes for housekeeping functions, such as energy production, amino acid metabolism, nucleotide metabolism, lipid transport, and translational machinery [ 48 ]. In contrast, the noncore (distributed, accessory, or adaptive) genome includes genes encoding for supplementary or modified biochemical functions that may be useful in contexts other than basic survival, such as adaptation to new environments, antibiotic resistance, or colonization of new environments and hosts [ 13 , 15 ].…”

“…The size of a species’ supragenome/pan-genome, relative to its core genome size, is highly variable among bacterial species. In an analysis of 295 species-specific supragenome projects published from 2005 to 2019, the supragenome was found to be substantially larger than the core genome in essentially all cases with the core genome making up from <20% to >60% of the supragenome [ 48 ] ( Figure 2 ). It is interesting to note that both genome and supragenome size are associated with a species biology.…”

“…Free-living environmental bacterial species tend to have the largest genomes 4–12 megabases (Mb); with commensal and pathogenic bacteria having intermediate size genomes 1.5–4 Mb; and obligate and intracellular pathogens having the smallest genomes 0.6–1.5 Mb. These rules, however, are not hard and fast as there are exceptions as not all pathogens have a reduced genome size [ 48 ].…”