Streptomyces bacteria are known for their prolific production of secondary metabolites, many of which have been widely used in human medicine, agriculture and animal health. To guide the effective prioritization of specific biosynthetic gene clusters (BGCs) for drug development and targeting the most prolific producer strains, knowledge about phylogenetic relationships of Streptomyces species, genome-wide diversity and distribution patterns of BGCs is critical. We used genomic and phylogenetic methods to elucidate the diversity of major classes of BGCs in 1,110 publicly available Streptomyces genomes. Genome mining of Streptomyces reveals high diversity of BGCs and variable distribution patterns in the Streptomyces phylogeny, even among very closely related strains. The most common BGCs are non-ribosomal peptide synthetases, type 1 polyketide synthases, terpenes, and lantipeptides. We also found that numerous Streptomyces species harbor BGCs known to encode antitumor compounds. We observed that strains that are considered the same species can vary tremendously in the BGCs they carry, suggesting that strain-level genome sequencing can uncover high levels of BGC diversity and potentially useful derivatives of any one compound. These findings suggest that a strain-level strategy for exploring secondary metabolites for clinical use provides an alternative or complementary approach to discovering novel pharmaceutical compounds from microbes.

Cooperation exists across all scales of biological organization, from genetic elements to complex human societies. Bacteria cooperate by secreting molecules that benefit all individuals in the population (i.e., public goods). Genes associated with cooperation can spread among strains through horizontal gene transfer (HGT). We discuss recent findings on how HGT mediated by mobile genetic elements promotes bacterial cooperation, how cooperation in turn can facilitate more frequent HGT, and how the act of HGT itself may be considered as a form of cooperation. We propose that HGT is an important enforcement mechanism in bacterial populations, thus creating a positive feedback loop that further maintains cooperation. To enforce cooperation, HGT serves as a homogenizing force by transferring the cooperative trait, effectively eliminating cheaters.

Members of the gram-positive bacterial genus Staphylococcus have historically been classified into coagulase-positive Staphylococcus (CoPS) and coagulase-negative Staphylococcus (CoNS) based on the diagnostic presentation of the coagulase protein. Previous studies have noted the importance of horizontal gene transfer (HGT) and recombination in the more well-known CoPS species Staphylococcus aureus, yet little is known of the contributions of these processes in CoNS evolution. In this study, we aimed to elucidate the phylogenetic relationships, genomic characteristics, and frequencies of HGT in CoNS, which are now being recognized as major opportunistic pathogens of humans. We compiled a data set of 1,876 publicly available named CoNS genomes. These can be delineated into 55 species based on allele differences in 462 core genes and variation in accessory gene content. CoNS species are a reservoir of transferrable genes associated with resistance to diverse classes of antimicrobials. We also identified nine types of the mobile genetic element SCCmec, which carries the methicillin resistance determinant mecA. Other frequently transferred genes included those associated with resistance to heavy metals, surface-associated proteins related to virulence and biofilm formation, type VII secretion system, iron capture, recombination, and metabolic enzymes. The highest frequencies of receipt and donation of recombined DNA fragments were observed in Staphylococcus capitis, Staphylococcus caprae, Staphylococcus hominis, Staphylococcus haemolyticus, and members of the Saprophyticus species group. The variable rates of recombination and biases in transfer partners imply that certain CoNS species function as hubs of gene flow and major reservoir of genetic diversity for the entire genus.

Salmonella is responsible for many nontyphoidal foodborne infections and enteric (typhoid) fever in humans. Of the two Salmonella species, Salmonella enterica is highly diverse and includes 10 known subspecies and approximately 2,600 serotypes. Understanding the evolutionary processes that generate the tremendous diversity in Salmonella is important in reducing and controlling the incidence of disease outbreaks and the emergence of virulent strains. In this study, we aim to elucidate the impact of homologous recombination in the diversification of S. enterica subspecies. Using a data set of previously published 926 Salmonella genomes representing the 10 S. enterica subspecies and Salmonella bongori, we calculated a genus-wide pan-genome composed of 84,041 genes and the S. enterica pan-genome of 81,371 genes. The size of the accessory genomes varies between 12,429 genes in S. enterica subsp. arizonae (subsp. IIIa) to 33,257 genes in S. enterica subsp. enterica (subsp. I). A total of 12,136 genes in the Salmonella pan-genome show evidence of recombination, representing 14.44% of the pan-genome. We identified genomic hot spots of recombination that include genes associated with flagellin and the synthesis of methionine and thiamine pyrophosphate, which are known to influence host adaptation and virulence. Last, we uncovered within-species heterogeneity in rates of recombination and preferential genetic exchange between certain donor and recipient strains. Frequent but biased recombination within a bacterial species may suggest that lineages vary in their response to environmental selection pressure. Certain lineages, such as the more uncommon non-enterica subspecies (non-S. enterica subsp. enterica), may also act as a major reservoir of genetic diversity for the wider population. IMPORTANCES. enterica is a major foodborne pathogen, which can be transmitted via several distinct routes from animals and environmental sources to human hosts. Multiple subspecies and serotypes of S. enterica exhibit considerable differences in virulence, host specificity, and colonization. This study provides detailed insights into the dynamics of recombination and its contributions to S. enterica subspecies evolution. Widespread recombination within the species means that new adaptations arising in one lineage can be rapidly transferred to another lineage. We therefore predict that recombination has been an important factor in the emergence of several major disease-causing strains from diverse genomic backgrounds and their ability to adapt to disparate environments.

Staphylococcus pseudintermedius is a commensal bacterium and a major opportunistic pathogen of dogs. The emergence of methicillin-resistant S. pseudintermedius (MRSP) is also becoming a serious concern. We carried out a population genomics study of 130 clinical S. pseudintermedius isolates from dogs and cats in the New England region of the United States. Results revealed the co-circulation of phylogenetically diverse lineages that have access to a large pool of accessory genes. Many MRSP and multidrug-resistant clones have emerged through multiple independent, horizontal acquisition of resistance determinants and frequent genetic exchange that disseminate DNA to the broader population. When compared to a Texas population, we found evidence of clonal expansion of MRSP lineages that have disseminated over large distances. These findings provide unprecedented insight into the diversification of a common cutaneous colonizer of man’s oldest companion animal and the widespread circulation of multiple high-risk resistant clones.