Clonal background and routes of plasmid transmission underlie antimicrobial resistance features of bloodstream Klebsiella pneumoniae.

Bloodstream infections caused by the opportunistic pathogen Klebsiella pneumoniae are associated with adverse health complications and high mortality rates. Antimicrobial resistance (AMR) limits available treatment options, thus exacerbating its public health and clinical burden. Here, we aim to elucidate the population structure of K. pneumoniae in bloodstream infections from a single medical center and the drivers that facilitate the dissemination of AMR. Analysis of 136 short-read genome sequences complemented with 12 long-read sequences shows the population consisting of 94 sequence types (STs) and 99 clonal groups, including globally distributed multidrug resistant and hypervirulent clones. In vitro antimicrobial susceptibility testing and in silico identification of AMR determinants reveal high concordance (90.44-100%) for aminoglycosides, beta-lactams, carbapenems, cephalosporins, quinolones, and sulfonamides. IncF plasmids mediate the clonal (within the same lineage) and horizontal (between lineages) transmission of the extended-spectrum beta-lactamase gene blaCTX-M-15. Nearly identical plasmids are recovered from isolates over a span of two years indicating long-term persistence. The genetic determinants for hypervirulence are carried on plasmids exhibiting genomic rearrangement, loss, and/or truncation. Our findings highlight the importance of considering both the genetic background of host strains and the routes of plasmid transmission in understanding the spread of AMR in bloodstream infections.

Five centuries of genome evolution and multi-host adaptation of Campylobacter jejuni in Brazil.

Consumption of raw, undercooked or contaminated animal food products is a frequent cause of Campylobacter jejuni infection. Brazil is the world's third largest producer and a major exporter of chicken meat, yet population-level genomic investigations of C. jejuni in the country remain scarce. Analysis of 221 C. jejuni genomes from Brazil shows that the overall core and accessory genomic features of C. jejuni are influenced by the identity of the human or animal source. Of the 60 sequence types detected, ST353 is the most prevalent and consists of samples from chicken and human sources. Notably, we identified the presence of diverse bla genes from the OXA-61 and OXA-184 families that confer beta-lactam resistance as well as the operon cmeABCR related to multidrug efflux pump, which contributes to resistance against tetracyclines, macrolides and quinolones. Based on limited data, we estimated the most recent common ancestor of ST353 to the late 1500s, coinciding with the time the Portuguese first arrived in Brazil and introduced domesticated chickens into the country. We identified at least two instances of ancestral chicken-to-human infections in ST353. The evolution of C. jejuni in Brazil was driven by the confluence of clinically relevant genetic elements, multi-host adaptation and clonal population growth that coincided with major socio-economic changes in poultry farming.

Demographic fluctuations in bloodstream Staphylococcus aureus lineages configure the mobile gene pool and antimicrobial resistance.

Staphylococcus aureus in the bloodstream causes high morbidity and mortality, exacerbated by the spread of multidrug-resistant and methicillin-resistant S. aureus (MRSA). We aimed to characterize the circulating lineages of S. aureus from bloodstream infections and the contribution of individual lineages to resistance over time. Here, we generated 852 high-quality short-read draft genome sequences of S. aureus isolates from patient blood cultures in a single hospital from 2010 to 2022. A total of 80 previously recognized sequence types (ST) and five major clonal complexes are present in the population. Two frequently detected lineages, ST5 and ST8 exhibited fluctuating demographic structures throughout their histories. The rise and fall in their population growth coincided with the acquisition of antimicrobial resistance, mobile genetic elements, and superantigen genes, thus shaping the accessory genome structure across the entire population. These results reflect undetected selective events and changing ecology of multidrug-resistant S. aureus in the bloodstream.

Ecology shapes the genomic and biosynthetic diversification of Streptomyces bacteria from insectivorous bats.

Streptomyces are prolific producers of secondary metabolites from which many clinically useful compounds have been derived. They inhabit diverse habitats but have rarely been reported in vertebrates. Here, we aim to determine to what extent the ecological source (bat host species and cave sites) influence the genomic and biosynthetic diversity of Streptomyces bacteria. We analysed draft genomes of 132 Streptomyces isolates sampled from 11 species of insectivorous bats from six cave sites in Arizona and New Mexico, USA. We delineated 55 species based on the genome-wide average nucleotide identity and core genome phylogenetic tree. Streptomyces isolates that colonize the same bat species or inhabit the same site exhibit greater overall genomic similarity than they do with Streptomyces from other bat species or sites. However, when considering biosynthetic gene clusters (BGCs) alone, BGC distribution is not structured by the ecological or geographical source of the Streptomyces that carry them. Each genome carried between 19-65 BGCs (median=42.5) and varied even among members of the same Streptomyces species. Nine major classes of BGCs were detected in ten of the 11 bat species and in all sites: terpene, non-ribosomal peptide synthetase, polyketide synthase, siderophore, RiPP-like, butyrolactone, lanthipeptide, ectoine, melanin. Finally, Streptomyces genomes carry multiple hybrid BGCs consisting of signature domains from two to seven distinct BGC classes. Taken together, our results bring critical insights to understanding Streptomyces-bat ecology and BGC diversity that may contribute to bat health and in augmenting current efforts in natural product discovery, especially from underexplored or overlooked environments.

Evolutionary dynamics of the accessory genomes of Staphylococcus aureus.

Staphylococcus aureus is a ubiquitous commensal and opportunistic bacterial pathogen that can cause a wide gamut of infections, which are exacerbated by the presence of multidrug-resistant and methicillin-resistant S. aureus. S. aureus is genetically heterogeneous and consists of numerous distinct lineages. Using 558 complete genomes of S. aureus, we aim to determine how the accessory genome content among phylogenetic lineages of S. aureus is structured and has evolved. Bayesian hierarchical clustering identified 10 sequence clusters, of which seven contained major sequence types (ST 1, 5, 8, 30, 59, 239, and 398). The seven sequence clusters differed in their accessory gene content, including genes associated with antimicrobial resistance and virulence. Focusing on the two largest clusters, BAPS8 and BAPS10, and each consisting mostly of ST5 and ST8, respectively, we found that the structure and connected components in the co-occurrence networks of accessory genomes varied between them. These differences are explained, in part, by the variation in the rates at which the two sequence clusters gained and lost accessory genes, with the highest rate of gene accumulation occurring recently in their evolutionary histories. We also identified a divergent group within BAPS10 that has experienced high gene gain and loss early in its history. Together, our results show highly variable and dynamic accessory genomes in S. aureus that are structured by the history of the specific lineages that carry them.IMPORTANCEStaphylococcus aureus is an opportunistic, multi-host pathogen that can cause a variety of benign and life-threatening infections. Our results revealed considerable differences in the structure and evolution of the accessory genomes of major lineages within S. aureus. Such genomic variation within a species can have important implications on disease epidemiology, pathogenesis of infection, and interactions with the vertebrate host. Our findings provide important insights into the underlying genetic basis for the success of S. aureus as a highly adaptable and resistant pathogen, which will inform current efforts to control and treat staphylococcal diseases.