ABSTRACT
BACKGROUND: Staphylococcus aureus can infect and adapt to multiple host species. However, our understanding of the genetic and evolutionary drivers of its generalist lifestyle remains inadequate. This is particularly important when considering local populations of S. aureus, where close physical proximity between bacterial lineages and between host species may facilitate frequent and repeated interactions between them. Here, we aim to elucidate the genomic differences between human- and animal-derived S. aureus from 437 isolates sampled from disease cases in the northeast region of the United States. RESULTS: Multi-locus sequence typing revealed the existence of 75 previously recognized sequence types (ST). Our population genomic analyses revealed heterogeneity in the accessory genome content of three dominant S. aureus lineages (ST5, ST8, ST30). Genes related to antimicrobial resistance, virulence, and plasmid types were differentially distributed among isolates according to host (human versus non-human) and among the three major STs. Across the entire population, we identified a total of 1,912 recombination events that occurred in 765 genes. The frequency and impact of homologous recombination were comparable between human- and animal-derived isolates. Low-frequency STs were major donors of recombined DNA, regardless of the identity of their host. The most frequently recombined genes (clfB, aroA, sraP) function in host infection and virulence, which were also frequently shared between the rare lineages. CONCLUSIONS: Taken together, these results show that frequent but variable patterns of recombination among co-circulating S. aureus lineages, including the low-frequency lineages, that traverse host barriers shape the structure of local gene pool and the reservoir of host-associated genetic variants. Our study provides important insights to the genetic and evolutionary factors that contribute to the ability of S. aureus to colonize and cause disease in multiple host species. Our study highlights the importance of continuous surveillance of S. aureus circulating in different ecological host niches and the need to systematically sample from them. These findings will inform development of effective measures to control S. aureus colonization, infection, and transmission across the One Health continuum.
Subject(s)
Gene Pool , Staphylococcal Infections , Animals , Multilocus Sequence Typing , Staphylococcus aureus/genetics , Biological EvolutionABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Anti-Bacterial Agents , Klebsiella Infections , Klebsiella pneumoniae , Microbial Sensitivity Tests , Plasmids , beta-Lactamases , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/pathogenicity , Plasmids/genetics , Humans , Klebsiella Infections/microbiology , Klebsiella Infections/transmission , Klebsiella Infections/epidemiology , Anti-Bacterial Agents/pharmacology , beta-Lactamases/genetics , Drug Resistance, Multiple, Bacterial/genetics , Bacteremia/microbiology , Bacteremia/transmission , Virulence/genetics , Carbapenems/pharmacologyABSTRACT
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.
Subject(s)
Campylobacter jejuni , Chickens , Evolution, Molecular , Genome, Bacterial , Campylobacter jejuni/genetics , Campylobacter jejuni/drug effects , Campylobacter jejuni/isolation & purification , Campylobacter jejuni/classification , Brazil , Animals , Chickens/microbiology , Humans , Campylobacter Infections/microbiology , Campylobacter Infections/veterinary , Host Adaptation/genetics , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , PhylogenyABSTRACT
Klebsiella oxytoca is an opportunistic pathogen causing serious nosocomial infections. Knowledge about the population structure and diversity of healthcare-associated K. oxytoca from a genomic standpoint remains limited. Here, we characterized the phylogenetic relationships and genomic characteristics of 20 K. oxytoca sensu stricto isolates recovered from bloodstream infections at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA from 2017 to 2021. Results revealed a diverse population consisting of 15 sequence types (STs) that together harbored 10 variants of the intrinsic beta-lactamase gene bla OXY-2, conferring resistance to penicillins. Similar sets of antimicrobial resistance (AMR) determinants reside in multiple distinct lineages, with no one lineage dominating the local population. To place the New Hampshire K. oxytoca in a broader context, we compared them to 304 publicly available genomes of clinical isolates from 18 countries. This global clinical K. oxytoca sensu stricto population is represented by over 65 STs that together harbored resistance genes against 14 antimicrobial classes, including eight bla OXY-2 variants. Three dominant STs in the global population (ST2, ST176, ST199) circulate across multiple countries and were also present in the New Hampshire population. The global K. oxytoca population is genetically diverse, but there is evidence for broad dissemination of a few lineages carrying distinct set of AMR determinants. Our findings reveal the clinical diversity of K. oxytoca sensu stricto and its importance in surveillance efforts aimed at monitoring the evolution of this drug-resistant nosocomial pathogen. IMPORTANCE The opportunistic pathogen Klebsiella oxytoca has been increasingly implicated in patient morbidity and mortality worldwide, including several outbreaks in healthcare settings. The emergence and spread of antimicrobial resistant strains exacerbate the disease burden caused by this species. Our study showed that clinical K. oxytoca sensu stricto is phylogenetically diverse, harboring various antimicrobial resistance determinants and bla OXY-2 variants. Understanding the genomic and population structure of K. oxytoca is important for international initiatives and local epidemiological efforts for surveillance and control of drug-resistant K. oxytoca.
ABSTRACT
Coagulase-negative Staphylococcus (CoNS) are opportunistic pathogens implicated in many human and animal infections. The evolutionary history of CoNS remains obscure because of the historical lack of recognition for their clinical importance and poor taxonomic sampling. Here, we sequenced the genomes of 191 CoNS isolates representing 15 species sampled from diseased animals diagnosed in a veterinary diagnostic laboratory. We found that CoNS are important reservoirs of diverse phages, plasmids and mobilizable genes encoding antimicrobial resistance, heavy metal resistance, and virulence. Frequent exchange of DNA between certain donor-recipient partners suggests that specific lineages act as hubs of gene sharing. We also detected frequent recombination between CoNS regardless of their animal host species, indicating that ecological barriers to horizontal gene transfer can be surmounted in co-circulating lineages. Our findings reveal frequent but structured patterns of transfer that exist within and between CoNS species, which are driven by their overlapping ecology and geographical proximity.
Subject(s)
Bacteriophages , Coagulase , Animals , Humans , Coagulase/genetics , Staphylococcus/genetics , PlasmidsABSTRACT
Microbes frequently encounter heavy metals and other toxic compounds generated from natural biogeochemical processes and anthropogenic activities. Here, we analyzed the prevalence and association of genes conferring resistance to heavy metals, biocides, and antimicrobial compounds in 394 genome sequences of clinical human-derived S. enterica from New Hampshire, USA. The most prevalent was the gold operon (gesABC-golTSB), which was present in 99.2% of the genomes. In contrast, the other five heavy metal operons (arsenic, copper, mercury, silver, tellurite) were present in 0.76% (3/394)-5.58% (22/394) of the total population. The heavy metal operons and three biocide resistance genes were differentially distributed across 15 sequence types (STs) and 16 serotypes. The number of heavy metal operons and biocide resistance genes per genome was significantly associated with high number of antimicrobial resistance (AMR) genes per genome. Notable is the mercury operon which exhibited significant association with genes conferring resistance to aminoglycosides, cephalosporins, diaminopyrimidine, sulfonamide, and fosfomycin. The mercury operon was co-located with the AMR genes aac(3)-IV, ant(3")-IIa, aph(3')-Ia, and aph(4)-Ia, CTX-M-65, dfrA14, sul1, and fosA3 genes within the same plasmid types. Lastly, we found evidence for negative selection of individual genes of each heavy metal operon and the biocide resistance genes (dN/dS < 1). Our study highlights the need for continued surveillance of S. enterica serotypes that carry those genes that confer resistance to heavy metals and biocides that are often associated with mobile AMR genes. The selective pressures imposed by heavy metals and biocides on S. enterica may contribute to the co-selection and spread of AMR in human infections.
ABSTRACT
Mammaliicoccus sciuri (previously Staphylococcus sciuri) is a frequent colonizer of mammals. We report the draft genomes of a methicillin-resistant strain (2254A) isolated from an armadillo and a methicillin-susceptible strain (6942A) from a cow. Genomes were sequenced using long-read Nanopore sequencing.