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The Twists and Turns of Pathogenic Spirochetes: Novel Insights for...
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The Twists and Turns of Pathogenic Spirochetes: Novel Insights for Prevention, Diagnosis and Treatment

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 23941

Special Issue Editor

Dr. Ryan O. M. Rego

E-Mail Website
Guest Editor
1. Institute of Parasitology, Biology Centre, Academy of Sciences of Czech Republic, Branisovska 31, 370 05 Ceske Budejovice, Czech Republic
2. Faculty of Science, University of South Bohemia, Branisovska 31, 370 05 Ceske Budejovice, Czech Republic
Interests: bacterial genetics; tick-borne diseases; vaccines; diagnostics; arthropod innate immunity; epidemiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

Spirochetes are an intriguing group of bacteria. Appearing very diverse when looking at their habitat, ecology, and in many instances their infectivity of vertebrate and non-vertebrate hosts, they are often considered together because of their similar cellular morphologies. They usually are long and thin and can be shaped like flat waves, helices, or more irregular morphologies. As mentioned, a large number of members of this group are known to be pathogens causing diseases worldwide such as Lyme disease, relapsing fever, syphilis, brachyspiral dysentery, and leptospirosis. They are all very different in their genomes which can be very segmented as in the Lyme disease Borrelia that have linear and circular plasmids besides the chromosome to a single circular genome in Treponema spp., the pathogen responsible for syphilis. Besides being unique among bacteria in their motility, which enables them to move within the tissue of their hosts, they also depend on a host of outer surface proteins for evasion of the innate and adaptive immune response within the host.

Spirochetes causing Lyme disease, relapsing fever, and leptospirosis are zoonotic in nature, with the first two mentioned having a tick host, which acts as a vector, within their zoonotic cycle. The identification and description of the adaptations required for pathogenic spirochetes to be able to enter, disseminate, persist, and infect is still very new, interesting, and challenging. An increased understanding in this field is fundamental to the discovery and implementation of strategies for better diagnosis, treatment, and prevention.

I would like to invite colleagues investigating any of the pathogenic spirochetes within the areas of their ecology, genetics, genomics, immunology, detection, public health, and vaccine development to submit their manuscripts to this Special Issue in the form of original research and reviews.

Dr. Ryan O. M. Rego
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • Borrelia
  • Leptospira
  • Treponema
  • Brachyspira
  • Leptospirosis
  • Syphilis
  • Relapsing fever
  • Lyme disease
  • Tick
  • Zoonotic diseases
  • Ecology
  • Host–pathogen Interactions
  • Public health

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Published Papers (5 papers)

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Research

Jump to: Review

20 pages, 1273 KiB  
Article
Immunoinformatic Study of Recombinant LigA/BCon1-5 Antigen and Evaluation of Its Diagnostic Potential in Primary and Secondary Binding Tests for Serodiagnosis of Porcine Leptospirosis
by Sujit Kumar Behera, Thankappan Sabarinath, Prasanta Kumar K. Mishra, Yosef Deneke, Ashok Kumar, Shanmugam ChandraSekar, Kuppusamy Senthilkumar, MedRam Verma, Balasubramanian Ganesh, Amol Gurav and Abhishek Hota
Pathogens 2021, 10(9), 1082; https://doi.org/10.3390/pathogens10091082 - 26 Aug 2021
Cited by 6 | Viewed by 3464
Abstract
Leptospirosis is responsible for hampering the productivity of swine husbandry worldwide. The aim of this study was to assess the efficacy of bioinformatics tools in predicting the three-dimensional structure and immunogenicity of recombinant LigBCon1-5 (rLigBCon1-5) antigen. A battery of bioinformatics tools such as [...] Read more.
Leptospirosis is responsible for hampering the productivity of swine husbandry worldwide. The aim of this study was to assess the efficacy of bioinformatics tools in predicting the three-dimensional structure and immunogenicity of recombinant LigBCon1-5 (rLigBCon1-5) antigen. A battery of bioinformatics tools such as I-TASSER, ProSA and SAVES v6.0 were used for the prediction and assessment of the predicted structure of rLigBCon1-5 antigen. Bepipred-2.0, DiscoTope v2.0 and ElliPro servers were used to predict linear and conformational epitopes while T-cell epitopes were predicted using NetMHCpan 4.1 and IEDB recommended 2.22 method for MHC Class I and II peptides respectively. The results obtained using various in silico methods were then compared with wet lab experiments comprising of both primary (IgG Dot ELISA Dipstick test) and secondary-binding assays (Latex Agglutination Test [LAT]) to screen 1153 porcine serum samples. The three-dimensional structure of rLigA/BCon1-5 protein as predicted by I-TASSER was found to be reliable by Ramachandran Plot and ProSA. The ElliPro server suggested 10 and three potential linear and conformational B-cell-epitopes, respectively, on the peptide backbone of the rLigA/BCon1-5 protein. The DiscoTope prediction server suggested 47 amino acid residues to be part of B-cell antigen. Ten of the most efficient peptides for MHC-I and II grooves were predicted by NetMHCpan 4.1 and IEDB recommended 2.22 method, respectively. Of these, three peptides can serve dual functions as it can fit both MHC I and II grooves, thereby eliciting both humoral-and cell-mediated immune responses. The prediction of these computational approaches proved to be reliable since rLigBCon1-5 antigen-based IgG Dot ELISA Dipstick test and LAT gave results in concordance to gold standard test, the Microscopic Agglutination Test (MAT), for serodiagnosis of leptospirosis. Both the IgG Dot ELISA Dipstick test and LAT were serodiagnostic assays ideally suited for peripheral level of animal health care system as “point of care” tests for the detection of porcine leptospirosis. Full article
(This article belongs to the Special Issue The Twists and Turns of Pathogenic Spirochetes: Novel Insights for Prevention, Diagnosis and Treatment)
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9 pages, 708 KiB  
Article
Treponema pallidum among Female Sex Workers: A Cross-Sectional Study Conducted in Three Major Cities in Northern Brazil
by Luiz Fernando Almeida Machado, Jacqueline Cortinhas Monteiro, Leonardo Quintão Siravenha, Marcelo Pereira Mota, Marlinda de Carvalho Souza, Adalto Sampaio dos Santos, Márcio Ronaldo Chagas Moreira, Rogério Valois Laurentino, Aldemir Branco Oliveira-Filho, Maria Alice Freitas Queiroz, Sandra Souza Lima, Ricardo Ishak and Marluísa de Oliveira Guimarães Ishak
Pathogens 2021, 10(8), 923; https://doi.org/10.3390/pathogens10080923 - 22 Jul 2021
Cited by 3 | Viewed by 2380
Abstract
Female sex workers (FSWs) are an important group of people vulnerable to sexually transmitted infections. Northern Brazil is a rural and socioeconomically underdeveloped region, with lack of epidemiological information on syphilis in key populations. This study investigated the prevalence and factors associated with [...] Read more.
Female sex workers (FSWs) are an important group of people vulnerable to sexually transmitted infections. Northern Brazil is a rural and socioeconomically underdeveloped region, with lack of epidemiological information on syphilis in key populations. This study investigated the prevalence and factors associated with exposure to Treponema pallidum among FSWs in three major cities in northern Brazil. This cross-sectional study was conducted with a convenience sample of 415 FSWs from the cities of Belém, Macapá, and Rio Branco. Blood samples and personal data were collected from January 2009 to August 2010. Rapid plasma reagin and immunoenzymatic assays were used to detect antibodies against T. pallidum. Logistic regression models were used to determine factors associated with exposure to T. pallidum. In total, 36.1% were exposed to T. pallidum, and 15.7% had active syphilis. Sexual risk behaviors, use of illicit drugs, low education, and reduced monthly income were associated with exposure to T. pallidum. The high rate of exposure to T. pallidum indicates the urgent need for measures to identify, treat, and prevent syphilis and an education program for the valuation, care, and social inclusion of FSWs in northern Brazil. Full article
(This article belongs to the Special Issue The Twists and Turns of Pathogenic Spirochetes: Novel Insights for Prevention, Diagnosis and Treatment)
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15 pages, 2592 KiB  
Article
Borrelia burgdorferi Surface Exposed GroEL Is a Multifunctional Protein
by Thomas Cafiero and Alvaro Toledo
Pathogens 2021, 10(2), 226; https://doi.org/10.3390/pathogens10020226 - 18 Feb 2021
Cited by 1 | Viewed by 3159
Abstract
The spirochete, Borrelia burgdorferi, has a large number of membrane proteins involved in a complex life cycle, that includes a tick vector and a vertebrate host. Some of these proteins also serve different roles in infection and dissemination of the spirochete in [...] Read more.
The spirochete, Borrelia burgdorferi, has a large number of membrane proteins involved in a complex life cycle, that includes a tick vector and a vertebrate host. Some of these proteins also serve different roles in infection and dissemination of the spirochete in the mammalian host. In this spirochete, a number of proteins have been associated with binding to plasminogen or components of the extracellular matrix, which is important for tissue colonization and dissemination. GroEL is a cytoplasmic chaperone protein that has previously been associated with the outer membrane of Borrelia. A His-tag purified B. burgdorferi GroEL was used to generate a polyclonal rabbit antibody showing that GroEL also localizes in the outer membrane and is surface exposed. GroEL binds plasminogen in a lysine dependent manner. GroEL may be part of the protein repertoire that Borrelia successfully uses to establish infection and disseminate in the host. Importantly, this chaperone is readily recognized by sera from experimentally infected mice and rabbits. In summary, GroEL is an immunogenic protein that in addition to its chaperon role it may contribute to pathogenesis of the spirochete by binding to plasminogen and components of the extra cellular matrix. Full article
(This article belongs to the Special Issue The Twists and Turns of Pathogenic Spirochetes: Novel Insights for Prevention, Diagnosis and Treatment)
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16 pages, 1685 KiB  
Article
Evaluation of Nucleoside Analogs as Antimicrobials Targeting Unique Enzymes in Borrelia burgdorferi
by Monideep Chakraborti, Samantha Schlachter, Shekerah Primus, Julie Wagner, Brandi Sweet, Zoey Carr, Kenneth A. Cornell and Nikhat Parveen
Pathogens 2020, 9(9), 678; https://doi.org/10.3390/pathogens9090678 - 20 Aug 2020
Cited by 5 | Viewed by 4584
Abstract
The first line therapy for Lyme disease is treatment with doxycycline, amoxicillin, or cefuroxime. In endemic regions, the persistence of symptoms in many patients after completion of antibiotic treatment remains a major healthcare concern. The causative agent of Lyme disease is a spirochete, [...] Read more.
The first line therapy for Lyme disease is treatment with doxycycline, amoxicillin, or cefuroxime. In endemic regions, the persistence of symptoms in many patients after completion of antibiotic treatment remains a major healthcare concern. The causative agent of Lyme disease is a spirochete, Borrelia burgdorferi, an extreme auxotroph that cannot exist under free-living conditions and depends upon the tick vector and mammalian hosts to fulfill its nutritional needs. Despite lacking all major biosynthetic pathways, B. burgdorferi uniquely possesses three homologous and functional methylthioadenosine/S-adenosylhomocysteine nucleosidases (MTANs: Bgp, MtnN, and Pfs) involved in methionine and purine salvage, underscoring the critical role these enzymes play in the life cycle of the spirochete. At least one MTAN, Bgp, is exceptional in its presence on the surface of Lyme spirochetes and its dual functionality in nutrient salvage and glycosaminoglycan binding involved in host-cell adherence. Thus, MTANs offer highly promising targets for discovery of new antimicrobials. Here we report on our studies to evaluate five nucleoside analogs for MTAN inhibitory activity, and cytotoxic or cytostatic effects on a bioluminescently engineered strain of B. burgdorferi. All five compounds were either alternate substrates and/or inhibitors of MTAN activity, and reduced B. burgdorferi growth. Two inhibitors: 5′-deoxy-5′-iodoadenosine (IADO) and 5′-deoxy-5′-ethyl-immucillin A (dEt-ImmA) showed bactericidal activity. Thus, these inhibitors exhibit high promise and form the foundation for development of novel and effective antimicrobials to treat Lyme disease. Full article
(This article belongs to the Special Issue The Twists and Turns of Pathogenic Spirochetes: Novel Insights for Prevention, Diagnosis and Treatment)
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Review

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17 pages, 1890 KiB  
Review
The Brilliance of Borrelia: Mechanisms of Host Immune Evasion by Lyme Disease-Causing Spirochetes
by Cassidy Anderson and Catherine A. Brissette
Pathogens 2021, 10(3), 281; https://doi.org/10.3390/pathogens10030281 - 2 Mar 2021
Cited by 30 | Viewed by 8613
Abstract
Lyme disease (LD) has become the most common vector-borne illness in the northern hemisphere. The causative agent, Borrelia burgdorferi sensu lato, is capable of establishing a persistent infection within the host. This is despite the activation of both the innate and adaptive immune [...] Read more.
Lyme disease (LD) has become the most common vector-borne illness in the northern hemisphere. The causative agent, Borrelia burgdorferi sensu lato, is capable of establishing a persistent infection within the host. This is despite the activation of both the innate and adaptive immune responses. B. burgdorferi utilizes several immune evasion tactics ranging from the regulation of surface proteins, tick saliva, antimicrobial peptide resistance, and the disabling of the germinal center. This review aims to cover the various methods by which B. burgdorferi evades detection and destruction by the host immune response, examining both the innate and adaptive responses. By understanding the methods employed by B. burgdorferi to evade the host immune response, we gain a deeper knowledge of B. burgdorferi pathogenesis and Lyme disease, and gain insight into how to create novel, effective treatments. Full article
(This article belongs to the Special Issue The Twists and Turns of Pathogenic Spirochetes: Novel Insights for Prevention, Diagnosis and Treatment)
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