DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for listeriosis — screening already-approved drugs against its 19-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleListeriosis maps to a 19-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for listeriosis is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) — HGS is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 2,3,4,6-tetrahydroxy-5-phosphonooxy-cyclohexyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AVX · 1.68 Å · ligand PHOSPHORIC ACID MONO-(2,3,4,6-TETRAHYDROXY-5-PHOSPHONOOXY-CYCLOHEXYL) ESTER (ITP). Experimental structure, not a prediction.
What the evidence adds up to
A retrospective study of 102 non-pregnant adults with listeriosis found that adding an aminoglycoside (gentamicin) to beta-lactam therapy did not improve survival. Overall mortality was 20.6%. Early mortality (days 3–14) was 27.3% in the combined therapy group versus 4.3% in the monotherapy group. Multivariate analysis identified renal failure, prior corticosteroid use, and age over 65 as predictors of early death; neoplastic disease and coma predicted late death. Gentamicin use was associated with a trend toward increased early mortality (odds ratio 3.40, 95% CI 0.82–14.07) and had no impact on late mortality.
In vitro checkerboard and kill-curve experiments with nine Listeria monocytogenes strains showed that diclofenac, a non-steroidal anti-inflammatory drug, was synergistic with gentamicin (fractional inhibitory concentration index 0.37) but indifferent with ampicillin (FIC 1). The difference in killing between the diclofenac-plus-gentamicin combination and either drug alone was statistically significant at 24 hours. No such synergy was seen with ampicillin.
Listeria monocytogenes is a food-borne pathogen that invades host cells, escapes into the cytosol, and replicates intracellularly using a set of well-characterised molecular mechanisms. The 2010 ISOPOL meeting reported ongoing work on these host-pathogen interactions, as well as novel uses of L. monocytogenes as an anti-cancer treatment and applications of transcriptional profiling and reporter gene fusions to study its biology.
What is still missing: prospective trials large enough to confirm or refute the retrospective finding that gentamicin may increase early mortality; clinical data on whether diclofenac plus gentamicin improves outcomes in patients, not just in broth; and any evidence that the anti-cancer use of Listeria translates to human listeriosis treatment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Antimicrobial Chemotherapy · 2009 · 86 citations
Predictors of mortality and impact of aminoglycosides on outcome in listeriosis in a retrospective cohort study
AbstractOBJECTIVES: Gentamicin is often used to treat listeriosis, particularly in patients with meningitis; nonetheless, some clinicians question this practice because of the drug's associated nephrotoxicity and inability to cross the blood-brain barrier. The aim of this study was to evaluate predictors of mortality and the impact of aminoglycosides on outcome in patients with listeriosis. METHODS: We conducted a retrospective study of all non-pregnant adult patients with Listeria monocytogenes infection detected in sterile body fluids between 1983 and 2006. Early mortality was defined as death occurring between days 3 and 14 after admission, and late mortality as in-hospital death after 14 days. RESULTS: Of 118 episodes, 16 were excluded because patients died in the first 48 h. Among the 102 patients analysed, 33 (32%) had received combined beta-lactam and aminoglycoside therapy and 69 (68%) beta-lactam monotherapy. Both groups had similar demographic and clinical features, and rate of appropriate initial therapy. Overall mortality was 21/102 (20.6%). Early overall mortality was 11.8%: 27.3% (9/33) in the combined group and 4.3% (3/69) in the monotherapy group (P = 0.003). Late mortality was 8.8%. In the multivariate analysis, the factors predicting early mortality were renal failure, previous corticosteroid therapy and age >65 years, whereas neoplastic disease and coma were associated with late mortality. Gentamicin administration did not decrease early mortality, but seemed to increase it. In the late mortality analysis, gentamicin use had no impact. In an analysis with the propensity score method for the use of aminoglycosides, combined therapy with this antibiotic was associated with an increasing trend for early mortality (OR 3.40, 95% CI 0.82-14.07). CONCLUSIONS: The addition of aminoglycosides to treatment for listeriosis did not improve the patients' outcome.
Letters in Applied Microbiology · 2009 · 17 citations
<i>In vitro</i>synergistic effect of gentamicin with the anti-inflammatory agent diclofenac against<i>Listeria monocytogenes</i>
AbstractAIMS: A total of nine Listeria monocytogenes strains (seven serotypes) were studied to ascertain whether the non-steroidal anti-inflammatory drug diclofenac (Dc) used in combination with the conventional antilisterial antibiotic gentamicin (Gm) or ampicillin (Am) synergistically augments the efficacy of the antibiotic in vitro. METHODS AND RESULTS: The effect of combination was evaluated by the checkerboard method to obtain a fractional inhibitory concentration (FIC) index followed by kill curves. Dc was synergistic with Gm (FIC 0.37) and there was indifference with Am (FIC 1) against L. monocytogenes ATCC 51774. The magnitude of the differences between killing by a single agent and the combination observed at 24 h was significant (P < 0.05) for Dc plus Gm but not Dc plus Am. CONCLUSIONS: Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in listeriosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Such findings may indicate parallel administration of anti-inflammatory and anti listeriosis drugs.
Bioengineered Bugs · 2010 · 3 citations · open access
<i>Listeria monocytogenes</i>
AbstractListeria monocytogenes is a highly adaptable food-borne pathogen that causes the life threatening illness listeriosis in infected individuals. Within the host this bacterium invades cells, escapes into the host cell cytosol and replicates intracellularly. To achieve this L. monocytogenes has evolved a sophisticated set of molecular weaponry that allows it to interact with and manipulate the cell biology of the host to its own advantage. Many of these interactions are well understood, putting this pathogen at the forefront of host-pathogen research, but fascinating new interactions are still emerging. The seventeenth International Symposium on Problems of Listeriosis (ISOPOL) was held in Portugal (Porto) in May of this year and this report describes some of the exciting developments that were presented at the meeting. The report focuses on developments in understanding the molecular interactions between L. monocytogenes and the host; it describes novel uses for L. monocytogenes as an anti-cancer treatment; and it describes some innovative uses of transcriptional profiling and reporter gene fusions that are helping illuminate our understanding of the basic biology of this important pathogen.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
