Comparative genomics of carbapenemase-producing <i>Morganella spp</i>
Bibliographic record
Abstract
ABSTRACT Background Morganella are opportunistic pathogens involved in various infections. In Morganella , intrinsic resistance to multiple antibiotics including colistin combined with the emergence of carbapenemase-producers (CP) strongly limits the antimicrobial armamentarium. Methods From 2013 to 2021, 172 highly drug-resistant (XDR) Morganella isolates from 8 European countries and Canada, two reference strains from the Pasteur Institute collection and two susceptible isolates were characterized by WGS, antimicrobial susceptibility testing and biochemical tests. Complete genomes from Genbank (n=103) were included for genomic analysis. Intrinsic resistance mechanism to polymyxins was deciphered by combining genetic analysis with mass spectrometry on the lipid A. Findings Morganella could be separated into 4 species named M. psychrotolerans, M. sibonii, M. morganii and a new species represented by a unique strain. Morganella morganii included two subspecies: M. morganii subsp. morganii (the most prevalent) and M. morganii subsp. intermedius . Intrinsic resistance to tetracycline and conservation of metabolic pathways correlated this refined taxonomy. CP were mostly identified among five ‘high-risk’ clones of M. morganii subsp. morganii . A single nucleotide polymorphism (SNP) cut-off of 100 was used to decipher outbreaks involving this species. Cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards the 172 XDR Morganella spp. isolates of our collection (including 145 CP) except for metallo-β-lactamase-producers. The intrinsic resistance to polymyxins corresponds to the addition of L-Ara4N on the lipid A. Interpretation This global characterization of the widest collection of XDR Morganella spp. highlighted the need to clarify the taxonomy, deciphered intrinsic resistance mechanisms and paved the way for further genomic comparisons. Funding None RESEARCH IN CONTEXT Evidence before this study On January 28 th 2022, we have searched for the terms “ Morganella ” and “carbapenemase” in all published reports available in PubMed with no language restriction. We identified a total of 43 articles and most of them (41/43) corresponded to a report of a single isolate of carbapenemase-producing Morganella morganii . Only one article aimed to decipher the antimicrobial susceptibility on a collection of Proteus, Providencia and Morganella isolated from global hospitalized patients with intra-abdominal and urinary tract infections. However, this collection only included 7 M. morganii isolates. On March 2021, when we finished the inclusions in our collection, only 104 genomes of Morganella spp. were available in the NCBI database. Since September 2021, very few reports were published on carbapenemase-producing Morganella with the exception of a study from Xiang G et al . reported 40 multi-drug resistant M. morganii isolates recovered from three hospitals in China from 2014 to 2020. Unfortunately, this collection included only two carbapenemase-producing M. morganii isolates (one OXA-48 and one IMP-1). A report of KPC-producing M. morganii in Japan and a longitudinal study of carbapemase-producing Enterobactrales in Taiwan that did not focused on Morganella. We also searched in PubMed for the terms ‘ Morganella sibonii ” or “ Morganella psychrotolerans ” in all published reports with no language restrictions. Our search identified a total of 20 articles. None of them was related to antimicrobial resistance and no study deciphered the Morganella spp. epidemiology on clinical isolates. Added values of this study This global characterization involved the widest collection of Morganella spp. isolates ever reported (barely doubling the number of Morganella spp. genomes in Genbank). In addition, 145 isolates of this worldwide collection made of 172 multidrug resistant Morganella spp. were carbapenemase producers for which therapeutic alternatives are scarce due to intrinsic resistance to last resort molecules, such as polymyxin. First, we found that cefepime-zidebactam and ceftazidime-avibactam were the most potent antimicrobials towards XDR Morganella spp. isolates except for metallo-β-lactamase-producers. Then, we observed that carbapenemase-encoding genes were present in different Morganella species highlighting necessary changes in the taxonomy. Morganella genus could be divided into 4 species named M. psychrotolerans, M. sibonii, M. morganii and a new species represented by a unique strain. Morganella morganii includes two subspecies: M. morganii subsp. morganii (the most prevalent) and M. morganii subsp. intermedius . We demonstrated that this refined taxonomy correlated with the intrinsic resistance to tetracycline, which was found only in M. sibonii , as well as several metabolic pathways ( e . g . trehalose assimilation, type III (T3SS) and type IV secretion system (T6SS), etc.…). In addition, we highlighted five “high-risk” clones of carbapenemase-producing M. morganii subsp. morganii that have already disseminated worldwide. Combining whole genome sequencing (WGS) data with epidemiological investigations, we demonstrated that a cut-off of 100 single nucleotide polymorphisms (SNPs) could be used to discriminate clonally-related from sporadic independ
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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 | 0.001 | 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".