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Cultivation Methods of Spirochetes from Borrelia burgdorferi Sensu Lato Complex and Relapsing Fever Borrelia
Published on: November 25, 2022
Interaction of spirochetes with the host fibrinolytic system and potential roles in pathogenesis
Mônica Larucci Vieira1, Ana Lucia T O Nascimento1
1a Centro de Biotecnologia, Instituto Butantan , Sao Paulo , Brazil.
Abstract:
The pathogenic spirochetes Borrelia burgdorferi, B. hermsii, B. recurrentis, Treponema denticola and Leptospira spp. are the etiologic agents of Lyme disease, relapsing fever, periodontitis and leptospirosis, respectively. Lyme borreliosis is a multi-systemic disorder and the most prevalent tick-borne disease in the northern hemisphere. Tick-borne relapsing fever is persistent in endemic areas worldwide, representing a significant burden in some African regions. Periodontal disease, a chronic inflammatory disorder that often leads to tooth loss, is caused by several potential pathogens found in the oral cavity including T. denticola. Leptospirosis is considered the most widespread zoonosis, and the predominant human disease in tropical, undeveloped regions. What these diseases have in common is that they are a significant burden to healthcare costs in the absence of prophylactic measures. This review addresses the interaction of these spirochetes with the fibrinolytic system, plasminogen (Plg) binding to the surface of bacteria and the generation of plasmin (Pla) on their surface. The consequences on host-pathogen interactions when the spirochetes are endowed with this proteolytic activity are discussed on the basis of the results reported in the literature. Spirochetes equipped with Pla activity have been shown to degrade extracellular matrix (ECM) components, in addition to digesting fibrin, facilitating bacterial invasion and dissemination. Pla generation triggers the induction of matrix metalloproteases (MMPs) in a cascade of events that enhances the proteolytic capacity of the spirochetes. These activities in concert with the interference exerted by the Plg/Pla on the complement system - helping the bacteria to evade the immune system - should illuminate our understanding of the mechanisms involved in host infection.
Insights
Pathogenic spirochetes like Borrelia and Leptospira bind plasminogen, generating plasmin on their surface. This proteolytic activity aids bacterial invasion, dissemination, and immune evasion, impacting diseases like Lyme disease and leptospirosis.
Area of Science:
- Microbiology
- Pathogen-host interactions
- Biochemistry
Background:
- Pathogenic spirochetes, including Borrelia burgdorferi, Treponema denticola, and Leptospira spp., cause significant global health burdens such as Lyme disease, periodontitis, and leptospirosis.
- These bacterial infections represent a considerable cost to healthcare systems due to the lack of effective prophylactic measures.
- A commonality among these spirochetal diseases is their interaction with the host's fibrinolytic system.
Purpose of the Study:
- To review the mechanisms by which pathogenic spirochetes interact with the fibrinolytic system, specifically plasminogen (Plg) binding and plasmin (Pla) generation.
- To discuss the consequences of this bacterial proteolytic activity on host-pathogen interactions and disease pathogenesis.
- To elucidate how spirochetes utilize Plg/Pla interactions to facilitate invasion, dissemination, and immune evasion.
Main Methods:
- Literature review of studies investigating spirochetal interactions with plasminogen and plasmin.
- Analysis of experimental data demonstrating the effects of bacterial-generated plasmin on host tissues and immune components.
- Synthesis of findings related to extracellular matrix degradation, matrix metalloproteinase induction, and complement system interference.
Main Results:
- Spirochetes bind plasminogen (Plg) and generate plasmin (Pla) on their surface, conferring proteolytic activity.
- Bacterial-generated plasmin degrades extracellular matrix (ECM) components and fibrin, facilitating bacterial invasion and spread.
- Plasmin generation induces matrix metalloproteinases (MMPs) and interferes with the complement system, aiding immune evasion.
Conclusions:
- The ability of spirochetes to harness the host's fibrinolytic system via Plg/Pla generation is a critical virulence factor.
- This proteolytic activity enhances bacterial pathogenesis by promoting tissue degradation, invasion, dissemination, and immune system evasion.
- Understanding these mechanisms is crucial for developing targeted therapies against spirochetal infections.
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