DeCure's autonomous AMR AI scientist is researching a drug-repurposing hypothesis for Borrelia infectious disease — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBorrelia infectious disease maps to a 4-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 borrelia infectious disease 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
matrix metallopeptidase 7 (MMP7) — MMP7 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Y6D · 1.6 Å · ligand N-[(2S)-1-[4-(5-BROMOPYRIDIN-2-YL)PIPERAZIN-1-YL]SULFONYL-5-PYRIMIDIN-2-YL-PENTAN-2-YL]-N-HYDROXY-METHANAMIDE (TQJ). Experimental structure, not a prediction.
What the evidence adds up to
A real-time semimultiplex PCR assay was developed that detects multiple relapsing fever Borrelia species and classifies them into three groups: soft-tick relapsing fever agents, the hard-tick-transmitted Borrelia miyamotoi, and louse-borne Borrelia recurrentis. The assay uses a single primer pair and multiple TaqMan probes, with an analytical limit of detection below 15 genome equivalents per reaction. Thirty isolates encompassing six species were accurately identified, and 39 of 41 residual clinical specimens (EDTA whole blood, serum, or plasma) from patients with relapsing fever were detected and correctly classified. None of 42 clinical samples from patients with other infections and 46 culture specimens from non-relapsing fever bacteria were detected.
A clinical case report described a patient diagnosed with Lyme borreliosis who initially responded to standard antibiotic therapy but experienced symptomatic rebound after treatment cessation and failed to respond to a second course of the same antibiotic. The patient was eventually diagnosed with both Borrelia and Anaplasma infections by serological testing in a private laboratory. Following a two-month course of combination antibiotic therapy, the patient responded clinically, with a return to almost normal functioning. The report discusses this case in the context of pre-clinical research examining potential Borrelial persistence despite antibiotic therapy.
An in vitro study using THP-1-derived macrophages exposed to four Borrelia species (Borrelia hermsii, Borrelia burgdorferi B31, B. burgdorferi NC-2, and Borrelia lonestari) measured intracellular and secreted interferon-gamma, interleukin-1β, interleukin-6, and tumour necrosis factor-alpha at 6, 24, and 48 hours. Treatment had a significant effect only on secreted TNF-alpha. Time point had a significant effect on intracellular IFN-γ, TNF-α and IL-6. However, no significant differences in the selected cytokines were found among the Borrelia species treatments; the model could not distinguish pathogenic from nonpathogenic borreliae using this limited cytokine panel.
A review of genetic manipulation tools for Borrelia notes that a robust molecular genetic toolbox has been constructed despite challenges including the highly segmented genome, complex growth requirements, and evolutionary distance from other genetically tractable bacteria. The authors state that some standard genetic tools remain elusive for Borrelia and mention these limitations. A general overview of Borrelia species notes they are agents of relapsing fever and Lyme disease, have a segmented genome consisting of a linear chromosome and a mix of linear and circular plasmids, and that members of the Lyme borreliosis group vary in their ability to cause disease and in clinical manifestations. Acrodermatitis chronica atrophicans is a common late manifestation of Lyme borreliosis in Europe. What remains missing is a larger panel of cytokines to test for distinguishing pathogenic from nonpathogenic borreliae, a reliable diagnostic approach for persistent infection after antibiotic therapy, and further development of genetic tools that remain unavailable for Borrelia.
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 Clinical Microbiology · 2021 · 8 citations · open access
Simultaneous Detection and Differentiation of Clinically Relevant Relapsing Fever <i>Borrelia</i> with Semimultiplex Real-Time PCR
Abstractspecies, present a significant diagnostic, clinical, and public health challenge due to their overlapping symptoms and the breadth of causative agents and arthropod vectors. The relapsing fever (RF) borreliae encompass both established and emerging pathogens and are transmitted to humans by soft ticks, hard ticks, or lice. We developed a real-time semimultiplex PCR assay that detects multiple RF borreliae causing human illness and classifies them into one of three groups. The groups are based on genetic similarity and include agents of soft-tick relapsing fever (Borrelia hermsii and others), the emerging hard-tick-transmitted pathogen B. miyamotoi, and the agent of louse-borne relapsing fever (B. recurrentis). The real-time PCR assay uses a single primer pair designed to amplify all known pathogenic RF borreliae and multiple TaqMan probes to allow the detection of and differentiation among the three groups. The assay detects all RF borreliae tested, with an analytical limit of detection below 15 genome equivalents per reaction. Thirty isolates of RF borreliae encompassing six species were accurately identified. Thirty-nine of 41 residual specimens (EDTA whole blood, serum, or plasma) from patients with RF were detected and correctly classified. None of 42 clinical samples from patients with other infections and 46 culture specimens from non-RF bacteria were detected. The development of a single-assay real-time PCR approach will help to improve the diagnosis of RF by simplifying the selection of tests to aid in the clinical management of acutely ill RF patients.
Potential Persistent Borrelia Infection and Response to Antibiotic Therapy; a Clinical Case Study and Review of Recent Literature
AbstractThis report describes the case of an individual who was clinically diagnosed with Lyme borreliosis and initially responded to standard antibiotic therapy. Subsequent to treatment cessation, the patient experienced symptomatic rebound and failed to respond to a second course of the same antibiotic. The patient was eventually diagnosed with both Borrelia and Anaplasma infections by serological testing performed in a private laboratory. Following a two-month course of combination antibiotic therapy, the patient responded clinically, with a return to almost normal functioning. We discuss this case in the context of recent pre-clinical research examining potential Borrelial persistence despite antibiotic therapy.
Vector-Borne and Zoonotic Diseases · 2016 · 4 citations · open access
Differentiated THP-1 Cells Exposed to Pathogenic and Nonpathogenic <i>Borrelia</i> Species Demonstrate Minimal Differences in Production of Four Inflammatory Cytokines
AbstractTick-borne borreliae include Lyme disease and relapsing fever agents, and they are transmitted primarily by ixodid (hard) and argasid (soft) tick vectors, respectively. Tick-host interactions during feeding are complex, with host immune responses influenced by biological differences in tick feeding and individual differences within and between host species. One of the first encounters for spirochetes entering vertebrate host skin is with local antigen-presenting cells, regardless of whether the tick-associated Borrelia sp. is pathogenic. In this study, we performed a basic comparison of cytokine responses in THP-1-derived macrophages after exposure to selected borreliae, including a nonpathogen. By using THP-1 cells, differentiated to macrophages, we eliminated variations in host response and reduced the system to an in vitro model to evaluate the extent to which the Borrelia spp. influence cytokine production. Differentiated THP-1 cells were exposed to four Borrelia spp., Borrelia hermsii (DAH), Borrelia burgdorferi (B31), B. burgdorferi (NC-2), or Borrelia lonestari (LS-1), or lipopolysaccharides (LPS) (activated) or media (no treatment) controls. Intracellular and secreted interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were measured using flow cytometric and Luminex-based assays, respectively, at 6, 24, and 48 h postexposure time points. Using a general linear model ANOVA for each cytokine, treatment (all Borrelia spp. and LPS compared to no treatment) had a significant effect on secreted TNF-α only. Time point had a significant effect on intracellular IFN-γ, TNF-α and IL-6. However, we did not see significant differences in selected cytokines among Borrelia spp. TREATMENTS: Thus, in this model, we were unable to distinguish pathogenic from nonpathogenic borreliae using the limited array of selected cytokines. While unique immune profiles may be detectable in an in vitro model and may reveal predictors for pathogenicity in borreliae of unknown pathogenicity, a larger panel of cytokines would be desirable to test.
Transactions of the Royal Society of Tropical Medicine and Hygiene · 1946 · 3 citations
Penicillin in the treatment of experimental relapsing fever in rats
Abstract1. Massive doses of penicillin administered over a short period were ineffective in the prophylactic treatment of Borrelia recurrentis infection in the white rat. 2. Intermittent prophylactic dosage appeared to prevent the development of of disease. 3. Intermittent dosage did not control the developed disease. 4. Persistence of the infection in the central nervous system of a rat was uninfluenced by relatively huge doses of penicillin administered early in the disease. 5. In vitro exposure of the spirochaetes to the action of high concentrations of penicillin did not affect their structure, motility or infectivity. 6. The above conclusions may only be applicable to certain strains of Borrelia, since other workers report success in the treatment of experimental relapsing fever with penicillin.
AbstractGenetic studies in Borrelia require special consideration of the highly segmented genome, complex growth requirements and evolutionary distance of spirochetes from other genetically tractable bacteria. Despite these challenges, a robust molecular genetic toolbox has been constructed to investigate the biology and pathogenic potential of these important human pathogens. In this chapter we summarize the tools and techniques that are currently available for the genetic manipulation of Borrelia, including the relapsing fever spirochetes, viewing them in the context of their utility and shortcomings. Our primary objective is to help researchers discern what is feasible and what is not practical when thinking about potential genetic experiments in Borrelia. We have summarized published methods and highlighted their critical elements, but we are not providing detailed protocols. Although many advances have been made since B. burgdorferi was first transformed over 25 years ago, some standard genetic tools remain elusive for Borrelia. We mention these limitations and why they persist, if known. We hope to encourage investigators to explore what might be possible, in addition to optimizing what currently can be achieved, through genetic manipulation of Borrelia.
AbstractAbstract Borrelia species constitute a heterogeneous group of organisms that are maintained in nature in animal reservoirs and are transmitted via arthropod vectors. Borrelia species are agents of relapsing fever (RF), caused by the RF Borrelia group, and Lyme disease, caused by the Lyme borreliosis (LB) Borrelia group. A hallmark of Borrelia species is a segmented genome consisting of a linear chromosome and a mix of linear and circular plasmids. Although members of LB group of Borrelia have similar characteristics, they vary in their ability to cause disease in humans as well as in clinical manifestations. Acrodermatitis chronica atrophicans is a common late manifestation of LB in Europe. RF Borrelia can be detected in peripheral blood with blood films prepared from blood collected with EDTA. Variable major protein‐like sequences expressed is one of the most specific Borrelia burgdorferi antigens and has high significance in LB serology.
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.
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