Immune Escape Strategies of
            <i>Borrelia Burgdorferi</i>

Aslam, Bilal; Nisar, Muhammad Atif; Khurshid, Mohsin; Salamat, Muhammad Khalid Farooq

doi:10.2217/fmb-2017-0013

Cited by 10 publications

(9 citation statements)

References 156 publications

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“…Immune evasion strategies used by Borrelia to establish infection have been extensively reviewed elsewhere [35,[156][157][158][159][160][161][162][163]. Thus, the detailed biochemistry of host subversion is beyond the scope of this communication.…”

Section: Immune Modulationmentioning

confidence: 99%

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

Bamm

Mainprize

et al. 2019

Pathogens

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Lyme disease is a complex tick-borne zoonosis that poses an escalating public health threat in several parts of the world, despite sophisticated healthcare infrastructure and decades of effort to address the problem. Concepts like the true burden of the illness, from incidence rates to longstanding consequences of infection, and optimal case management, also remain shrouded in controversy. At the heart of this multidisciplinary issue are the causative spirochetal pathogens belonging to the Borrelia Lyme complex. Their unusual physiology and versatile lifestyle have challenged microbiologists, and may also hold the key to unlocking mysteries of the disease. The goal of this review is therefore to integrate established and emerging concepts of Borrelia biology and pathogenesis, and position them in the broader context of biomedical research and clinical practice. We begin by considering the conventions around diagnosing and characterizing Lyme disease that have served as a conceptual framework for the discipline. We then explore virulence from the perspective of both host (genetic and environmental predispositions) and pathogen (serotypes, dissemination, and immune modulation), as well as considering antimicrobial strategies (lab methodology, resistance, persistence, and clinical application), and borrelial adaptations of hypothesized medical significance (phenotypic plasticity or pleomorphy).

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Section: Immune Modulationmentioning

confidence: 99%

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

Bamm

Mainprize

et al. 2019

Pathogens

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“…These serological tests are indirect diagnostic methods measuring the presence of anti- Bb antibodies (Abs) [ 25 ]. Unfortunately, these techniques have many limitations [ 26 ]. Bb sl is able to escape the immune system according to a large variety of mechanisms, inducing a reduced immune protection despite the activation of innate and adaptive immunity [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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

Guérin,

Shawky,

Zedan

et al. 2023

BMC Microbiol

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

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“…Genome comparisons further revealed that lipoprotein-encoding genes are the most variable loci within the genome, consistent with their roles in evading vector and host immunity [14]. For example, B. burgdorferi shifts its surface lipoprotein composition when migrating between the tick vector and the mammalian host, up-regulating the expression of outer surface protein A (OspA) during tick colonization, the expression of OspC during host invasion, and the expression of VlsE (Variable membrane protein-Like Sequence E) during persistency within the host [15,16].…”

Section: Antigenic Variations In Lyme Disease Pathogensmentioning

confidence: 91%

Maximum Antigen Diversification in a Lyme Bacterial Population and Evolutionary Strategies to Overcome Pathogen Diversity

Akther

Bezrucenkovas

et al. 2020

Preprint

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Natural populations of microbes and their hosts are engaged in an arms race in which microbes diversify to escape host immunity while hosts evolve novel immunity. This co-evolutionary process, known as the “Red Queen” hypothesis, poses a fundamental challenge to the development of broadly effective vaccines and diagnostics against a diversifying pathogen. Based on surveys of natural allele frequencies and experimental immunization of mice, we show minimal antigenic cross-reactivity among natural variants of the outer surface protein C (OspC), a dominant antigen of a Lyme Disease-causing bacterium (Borrelia burgdorferi). To overcome the challenge of OspC antigenic diversity to clinical development of preventive measures, we implemented a number of evolution-based strategies to broaden OspC immunological cross-reactivity. In particular, the centroid algorithm – a genetic algorithm to minimize sequence differences with natural variants – generated synthetic OspC analogs with the greatest promise as diagnostic and vaccine candidates against diverse Lyme pathogen strains coexisting in the Northeast United States. Mechanistically, we propose a model of runaway maximum antigen di-versification (MAD) mediated by amino-acid variations distributed across hypervariable regions on the OspC molecule. Under the MAD model, evolutionary centroids display high cross-reactivity by occupying the central void in the antigenic space excavated by diversifying natural variants. In contrast to the vaccine design based on concatenated epitopes, the centroid algorithm generates analogs of native antigens and is automated. The MAD model and evolution-inspired antigen designs have broad implications for combating diversifying pathogens driven by pathogen-host coevolution.ImportanceMicrobial pathogens rely on molecular diversity of cell surface antigens to escape host immunity. Vaccines based on one antigen variant often fail to protect the host against pathogens carrying other variants. Here we show evolution-based designs of synthetic antigens that are broadly reactive to all natural variants. The evolutionary analogs of a major surface antigen of a Lyme disease bacterium (Borrelia burgdorferi) showed promise as vaccine candidates against diverse pathogen strains coexisting in the endemic areas of Lyme disease in Northeast United States. Our evolution-based computational design is automated, generates molecular analogs of natural antigens, and opens a novel path to combating fast-evolving microbial pathogens.

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Immune Escape Strategies of Borrelia Burgdorferi

Cited by 10 publications

References 156 publications

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

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

Maximum Antigen Diversification in a Lyme Bacterial Population and Evolutionary Strategies to Overcome Pathogen Diversity

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