Population and pan-genomic analyses of <i>Staphylococcus pseudintermedius</i> identify geographic distinctions in accessory gene content and novel loci associated with AMR
Bibliographic record
Abstract
ABSTRACT Staphylococcus pseudintermedius is a common representative of the normal skin microbiota of dogs and cats but is also a causative agent of a variety of infections. Although primarily a canine/feline bacterium, recent studies suggest an expanded host range including humans. This paper details population genomic analyses of the largest yet assembled and sequenced collection of S. pseudintermedius isolates from across the USA and Canada and assesses these isolates within a larger global population genetic context. We then employ a pan-genome-wide association study analysis of over 1,700 S . pseudintermedius isolates from sick dogs and cats, covering the period 2017–2020, correlating loci at a genome-wide level, with in vitro susceptibility data for 23 different antibiotics. We find no evidence from either core genome phylogenies or accessory genome content for separate lineages colonizing cats or dogs. Some core genome geographic clustering was evident on a global scale, and accessory gene content was noticeably different between various regions, some of which could be linked to known antimicrobial resistance (AMR) loci for certain classes of antibiotics (e.g., aminoglycosides). Analysis of genes correlated with AMR was divided into different categories, depending on whether they were known resistance mechanisms, on a plasmid, or a putatively novel resistance mechanism on the chromosome. We discuss several novel chromosomal candidates for follow-up laboratory experimentation, including, for example, a bacteriocin (subtilosin), for which the same protein from Bacillus subtilis has been shown to be active against Staphylococcus aureus infections, and for which the operon, present in closely related Staphylococcus species, is absent in S. aureus . IMPORTANCE Staphylococcus pseudintermedius is an important causative agent of a variety of canine and feline infections, with recent studies suggesting an expanded host range, including humans. This paper presents global population genomic data and analysis of the largest set yet sequenced for this organism, covering the USA and Canada as well as more globally. It also presents analysis of in vitro antibiotic susceptibility testing results for the North American (NA) isolates, as well as genetic analysis for the global set. We conduct a pan-genome-wide association study analysis of over 1,700 S. pseudintermedius isolates from sick dogs and cats from NA to correlate loci at a genome-wide level with the in vitro susceptibility data for 23 different antibiotics. We discuss several chromosomal loci arising from this analysis for follow-up laboratory experimentation. This study should provide insight regarding the development of novel molecular treatments for an organism of both veterinary and, increasingly, human medical concern.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".