Disulfiram: Mechanisms, Applications, and Challenges

Antibiotics, Journal Year: 2023, Volume and Issue: 12(3), P. 524 - 524

Published: March 6, 2023

Background: Since disulfiram’s discovery in the 1940s and its FDA approval for alcohol use disorder, other indications have been investigated. This review describes potential clinical applications, associated risks, challenges. Methods: For this narrative review, a PubMed search was conducted articles addressing vivo studies of disulfiram with an emphasis on drug repurposing treatment human diseases. The key terms were “disulfiram” “Antabuse”. Animal vitro highlighting important mechanisms safety issues also included. Results: In total, 196 sources our research focus spanning 1948–2022 selected inclusion. addition to emerging data support role addictions (e.g., cocaine), infections bacteria such as Staphylococcus aureus Borrelia burgdorferi, viruses, parasites), inflammatory conditions, neurological diseases, cancers. side effects range from minor life-threatening, lower doses conveying less risk. Caution is needed due considerable inter-subject variability pharmacokinetics. Conclusions: While has promise “repurposed” agent disease, risk profile concern. well-controlled trials are assess efficacy non-alcohol-related indications.

Language: Английский

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Lyme borreliosis diagnosis: state of the art of improvements and innovations

BMC Microbiology, Journal Year: 2023, Volume and Issue: 23(1)

Published: Aug. 1, 2023

Abstract With almost 700 000 estimated cases each year in the United States and Europe, Lyme borreliosis (LB), also called disease, is most common tick-borne illness world. Transmitted by ticks of genus Ixodes caused bacteria Borrelia burgdorferi sensu lato, LB occurs with various symptoms, such as erythema migrans, which characteristic, whereas others involve blurred clinical features fatigue, headaches, arthralgia, myalgia. The diagnosis borreliosis, based on a standard two-tiered serology, subject many debates controversies, since it relies an indirect approach suffers from low sensitivity depending stage disease. Above all, early detection disease raises some issues. Inappropriate leads to therapeutic wandering, inducing potential chronic infection strong antibody response that fails clear infection. Early proper essential propose adequate treatment patients avoid persistence pathogen. This review presents available tests, emphasis improvements current diagnosis, innovative methods ideas which, ultimately, will allow more precise LB.

Language: Английский

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Tick-Borne Bacterial Diseases in Europe: Threats to public health

European Journal of Clinical Microbiology & Infectious Diseases, Journal Year: 2024, Volume and Issue: 43(7), P. 1261 - 1295

Published: April 27, 2024

Language: Английский

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Lyme disease and the pursuit of a clinical cure

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: May 24, 2023

Lyme disease, caused by the spirochete Borrelia burgdorferi , is most common vector-borne illness in United States. Many aspects of disease are still topics controversy within scientific and medical communities. One particular point debate etiology behind antibiotic treatment failure a significant portion (10–30%) patients. The condition which patients with continue to experience variety symptoms months years after recommended recently referred literature as post syndrome (PTLDS) or just simply (PTLD). commonly proposed mechanisms include host autoimmune responses, long-term sequelae from initial infection, persistence spirochete. aims this review will focus on vitro, vivo clinical evidence that either validates challenges these mechanisms, particularly regard role immune response resolution infection. Next generation treatments research into identifying biomarkers predict responses outcomes for also discussed. It essential definitions guidelines evolve translate diagnostic therapeutic advances patient care.

Language: Английский

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Borrelia burgdorferi loses essential genetic elements and cell proliferative potential during stationary phase in culture but not in the tick vector

Journal of Bacteriology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

ABSTRACT The Lyme disease agent Borrelia burgdorferi is a polyploid bacterium with segmented genome in which both the chromosome and over 20 distinct plasmids are present multiple copies per cell. This pathogen can survive for at least 9 months its tick vector an apparent dormant state between blood meals, without losing cell proliferative capability when re-exposed to nutrients. Cultivated B. cells grown stationary phase or resuspended nutrient-limited media often used study effects of nutrient deprivation. However, thorough assessment spirochete’s ability recover from depletion has been lacking. Our shows that starved cultures rapidly lose ability. Loss genetic elements essential proliferation contributes observed defect phase. gradual decline not perfectly synchronized chromosomes plasmids, generating harbor one more but lack all non-essential plasmids. phenomenon likely well-documented issue plasmid loss during vitro cultivation . In contrast, ticks 14 showed no evidence reduced loss. Beyond their practical implications studying , these findings suggest midgut offers unique environment supports maintenance ’s potential periods fasting. IMPORTANCE causes disease, prevalent tick-borne illness. must long (months year) dormancy meals. Resilience starvation common trait among bacteria. this reveals that, laboratory cultures, poorly endures loses viability. linked required proliferation. These results persistence nature shaped by environmental conditions than innate endure

Language: Английский

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Persistent Borrelia burgdorferi Sensu Lato Infection after Antibiotic Treatment: Systematic Overview and Appraisal of the Current Evidence from Experimental Animal Models

Clinical Microbiology Reviews, Journal Year: 2022, Volume and Issue: 35(4)

Published: Oct. 12, 2022

Lyme borreliosis is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato group, which are transmitted Ixodes tick species living in temperate climate zones of Northern Hemisphere. The clinical manifestations diverse and treated with oral or intravenous antibiotics.

Language: Английский

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Evidence for the Presence of Borrelia burgdorferi Biofilm in Infected Mouse Heart Tissues

Microorganisms, Journal Year: 2024, Volume and Issue: 12(9), P. 1766 - 1766

Published: Aug. 26, 2024

Borrelia burgdorferi, the bacterium responsible for Lyme disease, has been shown to form antimicrobial-tolerant biofilms, which protect it from unfavorable conditions. Bacterial biofilms are known significantly contribute severe inflammation, such as carditis, a common manifestation of disease. However, role B. burgdorferi in development carditis not thoroughly investigated due absence an appropriate model system. In this study, we examined heart tissues mice infected with presence and inflammatory markers using immunohistochemistry (IHC), combined fluorescence situ hybridization FISH/IHC, 3D microscopy, atomic force microscopy techniques. Our results reveal that spirochetes aggregates biofilm marker (alginate) mouse tissues. Furthermore, these induce indicated by elevated levels murine C-reactive protein near biofilms. This research provides evidence can tissue trigger processes, suggesting is valuable tool future studies on

Language: Английский

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The In Vitro Antimicrobial Susceptibility of Borrelia burgdorferi sensu lato: Shedding Light on the Known Unknowns

Pathogens, Journal Year: 2023, Volume and Issue: 12(10), P. 1204 - 1204

Published: Sept. 28, 2023

Human Lyme borreliosis (LB) represents a multisystem disorder that can progress in stages. The causative agents are transmitted by hard ticks of the Ixodes ricinus complex have been infected with spirochete Borrelia burgdorferi sensu lato. Today, LB is considered most important human tick-borne illness Northern Hemisphere. agent was identified and successfully isolated 1982 and, shortly thereafter, antibiotic treatment found to be safe efficacious. Since then, various vitro studies conducted order improve our knowledge activity antimicrobial against B. s. l. full spectrum susceptibility has still not defined for some more recently developed compounds. Moreover, current understanding interactions between agents, their possible mechanisms resistance remains very limited largely based on experiments only few isolates Borrelia. Even less known about persistence spirochetes exposed presence animal cell lines. Only relatively small number laboratory culture conducted. This review summarizes what It aims shed light unknowns continue fuel debates disease agents.

Language: Английский

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Renegade Bacterial Genetic Sequences in a Stealth Adapted Virus: Biological and Diagnostic Implications

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 12, 2022

There are major differences between viruses, bacteria, and eukaryotic cells in the structuring of their genomes, modes replication, capacity to horizontally transfer genetic sequences. DNA sequencing studies on a virus cultured from patient with chronic fatigue syndrome (CFS) have confirmed previously underappreciated certain viruses capture bacterial cellular sequences as part infectious process. The originated an African green monkey simian cytomegalovirus (SCMV). It is termed stealth adapted since infection not accompanied by inflammation. immune evasion attributed loss mutation genes coding for relatively few components that normally targeted system. This article provides further elucidation origins many bacterial-derived present virus. multiple clones close but non-identical sequence alignments different genomic regions Ochrobactrum quorumnocens A44 species bacteria. Another set matched most closely diverse Mycoplasma fermentans several other could only be approximately aligned those types clone 3B513 consistent contributions genomes term viteria refers bacteria-derived They likely primary cause CFS autism, act cofactors illnesses, including AIDS. As more general phenomenon renegade can lead mistaken diagnoses rather than viral diseases. important genetically additional patients wide range currently being Mycoplasma, Borrelia, or Streptococcal infections.

Language: Английский

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Comparison of the Efficacy of Longer versus Shorter Pulsed High Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome with Bartonellosis and Associated Coinfections

Microorganisms, Journal Year: 2023, Volume and Issue: 11(9), P. 2301 - 2301

Published: Sept. 12, 2023

Twenty-five patients with relapsing and remitting Borreliosis, Babesiosis, bartonellosis despite extended anti-infective therapy were prescribed double-dose dapsone combination (DDDCT), followed by one or several courses of High Dose Dapsone Combination Therapy (HDDCT). A retrospective chart review these 25 undergoing DDDCT HDDCT demonstrated that 100% improved their tick-borne symptoms, completing 6-7 day pulses had superior levels improvement versus 4-day if

Language: Английский

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