Dual population-level processes contribute to polyclonal ceftiofur heteroresistance in swine-derived <i>Escherichia coli</i>.
This study highlights the genetic complexity of ceftiofur resistance in swine-derived E. coli, with resistant subpopulations maintaining significant levels even without antibiotic pressure.
Where it sits
this study against the rest of the mazdutide (ibi362) corpusSummary and findings
This study investigated polyclonal ceftiofur heteroresistance in swine-derived Escherichia coli isolates. Four isolates were identified, each containing genetically distinct resistant and susceptible subpopulations. The study found that under ceftiofur pressure, resistant subpopulations expanded, with some maintaining proportions of approximately 43% under ceftiofur-free conditions.
Abstract
Antimicrobial resistance represents a major global health challenge. In veterinary medicine, ceftiofur is widely used to treat bacterial infections, yet its efficacy has been increasingly compromised by the dissemination of extended-spectrum <i>β</i>-lactamase (ESBL) genes such as <i>bla</i><sub>CTX-M</sub>. Although heteroresistance has been widely reported, its role in ceftiofur resistance, particularly in swine-derived <i>Escherichia coli</i>, remains poorly understood. Here, we identified four polyclonal ceftiofur heteroresistance (PCHR) <i>E. coli</i> isolates from swine, each comprising genetically distinct resistant and susceptible subpopulations. Whole-genome sequencing showed that all resistant subpopulations carried <i>bla</i><sub>CTX-M</sub> genes, and conjugation assays demonstrated that <i>bla</i><sub>CTX-M</sub>-carrying plasmids were transferable. Notably, in the resistant subpopulation EP91A, a chromosomal <i>bla</i><sub>CTX-M</sub>-containing fragment was identified in the transconjugant plasmid pTEP91A-1, with sequence features consistent with a possible <i>IS1380</i>-associated recombination event. Under ceftiofur pressure, resistant subpopulations expanded in all four PCHR isolates, although the associated population-level processes differed among isolates, including plasmid-mediated transfer and differential expansion of preexisting resistant subpopulations. Under ceftiofur-free conditions, resistant subpopulations were maintained at different levels, with EP70A and EP91A reaching higher proportions and stabilizing at approximately 43%, suggesting clone-associated population dynamics under antibiotic-free conditions. Transcriptomic analysis further identified clone-associated transcriptional differences between EP91A and EP91B across pathways related to environmental sensing, metabolism, transport, and cellular processes, providing hypothesis-generating observations. Collectively, these findings suggest that PCHR in these selected swine-derived <i>E. coli</i> isolates is associated with genetic heterogeneity, transferable <i>bla</i><sub>CTX-M</sub>-carrying plasmids, and distinct population dynamics, providing insights into ceftiofur resistance expansion and maintenance in heterogeneous bacterial populations.
Background
The study addresses the issue of antimicrobial resistance, specifically focusing on ceftiofur resistance in swine-derived Escherichia coli. Previous research has highlighted the role of extended-spectrum β-lactamase (ESBL) genes in resistance, but the mechanisms of heteroresistance in this context remain poorly understood. Understanding these mechanisms is crucial for addressing the challenges posed by antimicrobial resistance in veterinary medicine.
Methods
The study involved the identification of four polyclonal ceftiofur heteroresistance E. coli isolates from swine. Whole-genome sequencing was performed to analyze genetic features, and conjugation assays were used to assess plasmid transferability. The primary outcomes included the identification of resistant subpopulations and their dynamics under different antibiotic pressures.
Results
The primary endpoint revealed that resistant subpopulations expanded under ceftiofur pressure, with EP70A and EP91A stabilizing at approximately 43% resistant subpopulations in antibiotic-free conditions. Transcriptomic analysis indicated clone-associated transcriptional differences between EP91A and EP91B, although specific numeric data for these differences were not provided.
Interpretation
The findings suggest that polyclonal ceftiofur heteroresistance is linked to genetic heterogeneity and transferable plasmids. While the study provides valuable insights, the effect sizes regarding the clinical implications of these resistant subpopulations remain unclear. Limitations such as the lack of detailed statistical analysis and potential confounding factors may affect the conclusions drawn.
Key findings
- All resistant subpopulations carried bla_CTX-M genes.
- Ceftiofur pressure led to expansion of resistant subpopulations in all four PCHR isolates.
- EP70A and EP91A stabilized at approximately 43% resistant subpopulations under ceftiofur-free conditions.
Limitations
- Not reported in abstract.