Effects of topical corticosteroids and lidocaine on Borrelia burgdorferi sensu lato in mouse skin: potential impact to human clinical trials

Abstract

Lyme borreliosis is the most prevalent vector-borne disease in northern hemisphere. Borrelia burgdorferi sensu lato spirochetes are transmitted by Ixodes species ticks. During a blood meal, these spirochetes are inoculated into the skin where they multiply and often spread to various target organs: disseminated skin sites, the central nervous system, the heart and large joints. The usual diagnosis of this disease relies on serological tests. However, in patients presenting persistent clinical manifestations, this indirect diagnosis is not capable of detecting an active infection. If the serological tests are positive, it only proves that exposure of an individual to Lyme spirochetes had occurred. Although culture and quantitative PCR detect active infection, currently used tests are not sensitive enough for wide-ranging applications. Animal models have shown that B. burgdorferi persists in the skin. We present here our targeted proteomics results using infected mouse skin biopsies that facilitate detection of this pathogen. We have employed several novel approaches in this study. First, the effect of lidocaine, a local anesthetic used for human skin biopsy, on B. burgdorferi presence was measured. We further determined the impact of topical corticosteroids to reactivate Borrelia locally in the skin. This local immunosuppressive compound helps follow-up detection of spirochetes by proteomic analysis of Borrelia present in the skin. This approach could be developed as a novel diagnostic test for active Lyme borreliosis in patients presenting disseminated persistent infection. Although our results using topical corticosteroids in mice are highly promising for recovery of spirochetes, further optimization will be needed to translate this strategy for diagnosis of Lyme disease in patients.

Detection and quantification of bacterial species DNA in bovine digital dermatitis lesions in swabs and fine-needle aspiration versus biopsies

“…The M2 DD lesions assessed in this study are ulcerative, hemorrhagic, open wounds that lost completely the stratum corneum (11), which along with the application of sufficient pressure to obtain wound exudate using the swab allowed a greater detection of Treponema species DNA in this study. Although lidocaine has been suggested to have antimicrobial activities (29,30), it can affect microbial activities but not bacterial DNA detection by qPCR (31). Therefore, the use of lidocaine in this study prior to sampling collection is unlikely to affect our results.…”

Induced Transient Immune Tolerance in Ticks and Vertebrate Host: A Keystone of Tick-Borne Diseases?

“…skin. This has been particularly well-studied in Lyme disease (13), in mouse (314,315) and in dog model (319). It will be very interesting to perform similar analyses in human.…”

“…It would be interesting to investigate the potential signification of this peak, perhaps related to generation of immune tolerance in the host skin. In animal models, induction of immune tolerance to pathogens seems to develop and pathogens persist in the skin in absence of antibiotics (314). This has been particularly well-documented for Borrelia in the mouse model.…”

“…This has been particularly well-documented for Borrelia in the mouse model. The pathogen is alive since it can be reactivated by application of topical corticosteroid that induces a local immunosuppression and local multiplication of Borrelia (314,315). In experimental inoculation of luciferase positive-Borrelia, the bacteria can be visualized moving extracellularly in mouse skin for several months (M. Wooten-personal communication).…”

New geographical records for tick‐borne pathogens in ticks collected from cattle in Benin and Togo

“…Borrelia burgdorferi s.l. is one of the most important tick‐borne zoonotic agents in humans (Lefeuvre et al., 2020 ). They are maintained in nature by the interaction that exists with its vector ticks vertebrate reservoir hosts.…”