2187. Earliest Description of Mobile Genetic Elements (MGEs) Involved in Establishing <i>bla</i>NDM Persistence Following its Spread From <i>Acinetobacter</i> spp. to Enterobacterales
Bibliographic record
Abstract
Abstract Background bla NDM is the most prevalent carbapenemase worldwide. It originated in Acinetobacter spp. and spread to Enterobacterales on MGEs despite bottlenecks in MGE transfers between, and persistence within, these phylogenetically distinct bacteria. To elucidate how this transfer and successful expansion were achieved, we investigated MGEs among the earliest NDM-positive Gram-negative bacteria (GNB), isolated in India in 2007. Methods Thirteen polymerase chain reaction-confirmed NDM-positive GNB underwent whole-genome sequencing (Illumina NovaSeq and Oxford Nanopore Technologies MinION) and computational analyses: assembly (Unicycler and Trycycler), annotation (RAST), identification (Kraken2), plasmid incompatibility (PlasmidFinder). Results Single copies of blaNDM-1 were found in 12 Enterobacterales (6 K. pneumoniae; 3 E. coli; 2 E. cloacae; 1 E. hormaechei) and 1 A. baumannii (Ab), located on plasmids in 11/13 strains: 6 IncC, 3 IncFII, 2 IncFIB (Figure 1). Partial or complete ISAba125 was found upstream of all blaNDM, with a second complete downstream copy forming Tn125 only in Ab. blaNDM's genetic environment was highly diverse including the earliest evidence of its association with MGEs that participated in its global dissemination: insertion sequence common region 1 (ISCR1, n=5) and Tn3000 (n=4). IS3000, present in 2 copies bracketing Tn3000, was also found in single copies in 4 strains at varying distances upstream of blaNDM. In 3/4 of these, ISCR1 was downstream of blaNDM. These hybrid constructs may represent precursors leading to the formation of these MGEs, or degenerate structures. Figure 1: Genetic environment surrounding blaNDM in 13 Gram-negative bacteria isolated in India in 2007. Acibau: Acinetobacter baumannii; Entclo: Enterobacter cloacae; Enthor: Enterobacter hormaechei; Esccol: Escherichia coli; Klepne: Klebsiella pneumoniae. Conclusion We present evidence of early, rapid and diverse adaptation of blaNDM’s genetic environment following its transfer from Acinetobacter spp. to Enterobacterales. We identify for the first time potentially intermediate genetic structures in the transition between the ancestral Tn125 structure from Acinetobacter spp., and both ISCR1 and Tn3000, which overtook Tn125 as the predominant MGEs among NDM-positive Enterobacterales. Additional sequencing of early NDM-positive isolates could shed more light on the genetic events leading to the formation of MGEs associated with blaNDM, furthering our understanding of the emergence of MGEs carrying antibiotic-resistance genes. Disclosures All Authors: No reported disclosures
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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) | 0.002 | 0.001 |
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".