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17 pages, 5435 KiB

Open AccessArticle

Prediction, Synthesis and Evaluation of a Synthetic Peptide as an Enzyme-Linked Immunosorbent Assay (ELISA) Candidate for Screening of Bovine Antibodies against Theileria annulata

by Prasanta Kumar Koustasa Mishra, Anupama Jena, Souti Prasad Sarkhel, Sujit Kumar Behera, Annada Das, Thankappan Sabarinath, Dayanidhi Jena, Kruti Debnath Mandal, Adhikari Sahu, Anshuman Kumar, Vinod Kumar, Rahul Ganpatrao Kadam, Srinivas Sathapathy and Thavitiki Prasada Rao

Microorganisms 2023, 11(11), 2663; https://doi.org/10.3390/microorganisms11112663 - 30 Oct 2023

Viewed by 1066

Abstract

Tick-borne diseases (TBDs) of livestock are endemic across various parts of tropical countries. Theileriosis is one such economically important TBD, caused by the Theileriidae family of organisms, which is transmitted by ticks. Theileria annulata, the causative agent of tropical theileriosis, contributes a [...] Read more.

Tick-borne diseases (TBDs) of livestock are endemic across various parts of tropical countries. Theileriosis is one such economically important TBD, caused by the Theileriidae family of organisms, which is transmitted by ticks. Theileria annulata, the causative agent of tropical theileriosis, contributes a significant loss to the dairy sector by causing anorexia, high fever, anemia, inflammatory changes in vital organs and icterus, thus, a loss in milk yield. Though vaccines are available, their protective efficacy is not absolute, and treatment is limited to early diagnosis of the causative agent. Routinely, microscopic identification of piroplasms in the erythrocytes (Giemsa-stained) of infected animals or schizonts in lymph node biopsies are practiced for diagnosis. PCR-based techniques (multiplex, uniplex, nested and real-time) have been reported to perform well in diagnosing active infection. Several attempts have been made using serological assays like Dot blot, ELISA and ICT, but the results were of variable sensitivity and specificity. Recombinant proteins like the Theileria annulata merozoite surface antigen (Tams1) and Theileria annulata surface protein (TaSP) have been explored as antigenic candidates for these assays. In the present study, we predicted an immunogenic peptide, i.e., TaSP-34, from the TaSP using various computational tools. The predicted peptide was custom synthesized. The diagnostic potential of the peptide was assessed by indirect plate ELISA to detect the bovine-IgM against Theileria annulata. Alongside, a recombinant truncated TaSP (rTaSP(tr)) was expressed and purified, which was used to compare the performance of the peptide as a diagnostic candidate. The IgM-based peptide ELISA was 100% sensitive and 92.77% specific as compared to PCR (Tams1 targeting), while 98.04% sensitivity and 97.44% specificity were observed in comparison with rTaSP(tr) ELISA. Almost perfect agreement between peptide ELISA and Tams1 PCR was observed with a Cohen’s kappa coefficient (κ-value) of 0.901 and agreement of 95.31%. Further, the κ-value between the peptide ELISA and rTaSP(tr) ELISA was found to be 0.95, and the agreement was 97.65%, which shows a good correlation between the two tests. The findings suggest that the TaSP-34 peptide can be an efficient and new-generation diagnostic candidate for the diagnosis of T. annulata. Furthermore, the peptide can be synthesized commercially at a larger scale and can be a cost-effective alternative for the protein-based diagnostic candidates for T. annulata. Full article

(This article belongs to the Special Issue Emerging Research on Tick-Borne Pathogens and Diseases)

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20 pages, 3017 KiB

Open AccessArticle

A Longitudinal Study of a Large Clinical Cohort of Patients with Lyme Disease and Tick-Borne Co-Infections Treated with Combination Antibiotics

by David Xi, Abbie Thoma, Minha Rajput-Ray, Anne Madigan, Gordana Avramovic, Kunal Garg, Leona Gilbert and John S. Lambert

Microorganisms 2023, 11(9), 2152; https://doi.org/10.3390/microorganisms11092152 - 24 Aug 2023

Cited by 2 | Viewed by 4780

Abstract

The rising prevalence of tick-borne infections (TBIs) necessitates further attention. This study retrospectively investigated the types of TBIs, symptoms, and if combination antibiotics were helpful within a patient cohort at an infectious disease clinic in Ireland. In this chart audit of 301 individuals [...] Read more.

The rising prevalence of tick-borne infections (TBIs) necessitates further attention. This study retrospectively investigated the types of TBIs, symptoms, and if combination antibiotics were helpful within a patient cohort at an infectious disease clinic in Ireland. In this chart audit of 301 individuals (184 female, 117 male) tested for TBIs, 140 (46.51%) had positive antibody responses for TBIs from an ELISA (enzyme-linked immunoassay) that was based on a modified two-tiered testing protocol. A total of 93 (66.43%) patients had positive antibody responses to one TBI: 83 (59.29%) for Borrelia, 7 (5.00%) for Rickettsia, and 1 (0.71%) each for either Babesia, Bartonella, or Ehrlichia. The remaining 47 (33.57%) patients were infected with multiple TBIs. These patients were treated with combination antibiotics and monitored at two subsequent follow-ups. Only 2 of 101 patients (1.98%) had discontinued treatment by the second follow-up. In the first follow-up with 118 patients, 70 (59.32%) reported pain and 48 (40.68%) had neurological symptoms. In the next follow-up of 101 patients, 41 (40.59%) had pain while 30 (29.70%) had neurological symptoms. There were statistically significant reductions in the incidence of pain (41.43%) and neurological (37.50%) symptoms between follow-ups. Thus, our study demonstrates that combination antibiotics effectively relieve TBI symptoms with good patient tolerance. Full article

(This article belongs to the Special Issue Emerging Research on Tick-Borne Pathogens and Diseases)

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14 pages, 1101 KiB

Open AccessArticle

Tick Species Diversity and Molecular Identification of Spotted Fever Group Rickettsiae Collected from Migratory Birds Arriving from Africa

by Elisa Mancuso, Marco Di Domenico, Luigina Di Gialleonardo, Michela Menegon, Luciano Toma, Marco Di Luca, Francesca Casale, Guido Di Donato, Laura D’Onofrio, Angela De Rosa, Sara Riello, Andrea Ferri, Lorenzo Serra and Federica Monaco

Microorganisms 2023, 11(8), 2036; https://doi.org/10.3390/microorganisms11082036 - 8 Aug 2023

Cited by 1 | Viewed by 1094

Abstract

The role of migratory birds in the spread of ticks and tick-borne pathogens along their routes from Africa to Europe is increasingly emerging. Wild birds can host several tick species, often infected by bacteria responsible for zoonoses. The aim of the study is [...] Read more.

The role of migratory birds in the spread of ticks and tick-borne pathogens along their routes from Africa to Europe is increasingly emerging. Wild birds can host several tick species, often infected by bacteria responsible for zoonoses. The aim of the study is to assess the possible introduction of exotic ticks carried by migratory birds into Italy from Africa and to detect the presence of Rickettsia species and Coxiella burnetii they may harbor. During a two-year survey, we collected ticks from migratory birds captured during their short stop-over on Ventotene Island. Specimens were first identified by morphology or sequencing molecular targets when needed, and then tested by real-time PCR for the presence of selected pathogens. A total of 91% of the collection consisted of sub-Saharan ticks, more than 50% of which were infected by Rickettsia species belonging to the spotted fever group, mainly represented by R. aeschlimannii. In contrast, the suspected C. burnetii detected in two soft ticks were confirmed as Coxiella-like endosymbionts and not the pathogen. Although there are still gaps in the knowledge of this dispersal process, our findings confirm the role of migratory birds in the spread of ticks and tick-borne pathogens, suggesting the need for a continuous surveillance to monitor the potential emergence of new diseases in Europe. Full article

(This article belongs to the Special Issue Emerging Research on Tick-Borne Pathogens and Diseases)

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12 pages, 1661 KiB

Open AccessArticle

Molecular Evidence of Rickettsia conorii subsp. raoultii and Rickettsia felis in Haemaphysalis intermedia Ticks in Sirumalai, Eastern Ghats, Tamil Nadu, South India

by Krishnamoorthy Nallan, Veerapathiran Ayyavu, Elango Ayyanar, Balaji Thirupathi, Bhavna Gupta, Panneer Devaraju, Ashwani Kumar and Paramasivan Rajaiah

Microorganisms 2023, 11(7), 1713; https://doi.org/10.3390/microorganisms11071713 - 30 Jun 2023

Cited by 2 | Viewed by 1333

Abstract

Rickettsia is an important pathogenic entity among tick-borne diseases (TBD), which are considered serious emerging public health problems globally. In India, though the widespread distribution of ticks and TBD has been documented, its real burden remains underreported. In a preliminary attempt, rickettsial surveillance [...] Read more.

Rickettsia is an important pathogenic entity among tick-borne diseases (TBD), which are considered serious emerging public health problems globally. In India, though the widespread distribution of ticks and TBD has been documented, its real burden remains underreported. In a preliminary attempt, rickettsial surveillance was carried out in ticks collected from Sirumalai, Eastern Ghats in Tamil Nadu, India by using pathogen genome-based phylogenetic inferences generated through multi-locus sequence typing (MLST), targeting the genes 16s rRNA, OmpA, OmpB, and gltA by nested PCR. The laboratory evidence confirms the circulation of Rickettsia in Haemaphysalis intermedia species collected from this area. Analysis of the four gene sequences detected demonstrates their closest identity to the spotted fever group (SFG) available in the GenBank database. Further, multiple sequence alignment with other sequences derived from the GenBank database showed close relatedness to Rickettsia conorii subsp. raoultii (16s rDNA-99.32%, OmpA-93.38%, OmpB-97.39%, and gltA-98.57%) and Rickettsia felis (16s rDNA 99.54%, OmpA-100%, OmpB-100% and gltA-99.41%). With this genomic evidence, the circulation of rickettsial pathogens in the pools of H. intermedia ticks infesting livestock in the Sirumalai foothill area has been demonstrated and to complement the microscopic identification of the tick species, DNA barcodes were generated for H. intermedia using the mitochondrial cytochrome c oxidase subunit I gene (COI). Nevertheless, R. raoultii and R. felis were found to be the aetiological agents of tick-borne lymphadenopathy and flea-borne spotted fever in human cases, respectively, further study on the determination of their diversity, distribution, clinical relevance, and potential risk to the local community in these areas is highly warranted. Full article

(This article belongs to the Special Issue Emerging Research on Tick-Borne Pathogens and Diseases)

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12 pages, 1339 KiB

Open AccessArticle

Diversification of Bourbon Virus in New York State

by Rachel E. Lange, Alan P. Dupuis II and Alexander T. Ciota

Microorganisms 2023, 11(6), 1590; https://doi.org/10.3390/microorganisms11061590 - 15 Jun 2023

Cited by 1 | Viewed by 1477

Abstract

Bourbon virus (BRBV, family Orthomyxoviridae) is a tickborne virus recently detected in the United States (US). BRBV was first identified from a fatal human case in 2014 in Bourbon County, Kansas. Enhanced surveillance in Kansas and Missouri implicated Amblyomma americanum as the [...] Read more.

Bourbon virus (BRBV, family Orthomyxoviridae) is a tickborne virus recently detected in the United States (US). BRBV was first identified from a fatal human case in 2014 in Bourbon County, Kansas. Enhanced surveillance in Kansas and Missouri implicated Amblyomma americanum as the primary vector for BRBV. Historically, BRBV was only detected in the lower midwestern US, but since 2020 it has been reported in North Carolina, Virginia, New Jersey, and New York State (NYS). This study aimed to elucidate genetic and phenotypic characteristics of BRBV strains from NYS through whole genome sequencing and the assessment of replication kinetics in mammalian cultures and A. americanum nymphs. Sequence analysis revealed the existence of two divergent BRBV clades circulating in NYS. BRBV NY21-2143 is closely related to the midwestern BRBV strains but has unique substitutions in the glycoprotein. Two other NYS BRBV strains, BRBV NY21-1814 and BRBV NY21-2666, form a distinct clade unique from previously sequenced BRBV strains. Phenotypic diversification was also detected in NYS BRBV strains compared to each other and midwestern BRBV strains, with BRBV NY21-2143 displaying attenuation in rodent-derived cell culture and a fitness advantage in experimentally infected A. americanum. These data suggest genetic and phenotypic diversification of emergent BRBV strains circulating in NYS that could contribute to increased spread of BRBV in the northeastern US. Full article

(This article belongs to the Special Issue Emerging Research on Tick-Borne Pathogens and Diseases)

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18 pages, 1879 KiB

Open AccessArticle

Effect of Borrelia burgdorferi on the Expression of miRNAs in Breast Cancer and Normal Mammary Epithelial Cells

by Ananya Debbarma, Miranda Mansolf, Vishwa A. Khatri, Justine A. Valentino and Eva Sapi

Microorganisms 2023, 11(6), 1475; https://doi.org/10.3390/microorganisms11061475 - 1 Jun 2023

Cited by 2 | Viewed by 4233

Abstract

Breast cancer is one of the leading causes of death in women worldwide. Recent studies have demonstrated that inflammation due to infections with microorganisms could play a role in breast cancer development. One of the known human pathogens, Borrelia burgdorferi, the causative [...] Read more.

Breast cancer is one of the leading causes of death in women worldwide. Recent studies have demonstrated that inflammation due to infections with microorganisms could play a role in breast cancer development. One of the known human pathogens, Borrelia burgdorferi, the causative agent of Lyme disease, has been shown to be present in various types of breast cancer and is associated with poor prognosis. We reported that B. burgdorferi can invade breast cancer cells and affect their tumorigenic phenotype. To better understand the genome-wide genetic changes caused by B. burgdorferi, we evaluated the microRNA (miRNA or miR) expression profiles of two triple-negative breast cancer cell lines and one non-tumorigenic mammary cell line before and after B. burgdorferi infection. Using a cancer-specific miRNA panel, four miRNAs (miR-206, 214-3p, 16-5p, and 20b-5p) were identified as potential markers for Borrelia-induced changes, and the results were confirmed by quantitative real-time reverse transcription (qRT-PCR). Among those miRNAs, miR-206 and 214 were the most significantly upregulated miRNAs. The cellular impact of miR-206 and 214 was evaluated using DIANA software to identify related molecular pathways and genes. Analyses showed that the cell cycle, checkpoints, DNA damage–repair, proto-oncogenes, and cancer-related signaling pathways are mostly affected by B. burgdorferi infection. Based on this information, we have identified potential miRNAs which could be further evaluated as biomarkers for tumorigenesis caused by pathogens in breast cancer cells. Full article

(This article belongs to the Special Issue Emerging Research on Tick-Borne Pathogens and Diseases)

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Review

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24 pages, 425 KiB

Open AccessReview

The Use of Natural Bioactive Nutraceuticals in the Management of Tick-Borne Illnesses

by Samuel M. Shor and Sunjya K. Schweig

Microorganisms 2023, 11(7), 1759; https://doi.org/10.3390/microorganisms11071759 - 5 Jul 2023

Viewed by 11845

Abstract

The primary objective of this paper is to provide an evidence-based update of the literature on the use of bioactive phytochemicals, nutraceuticals, and micronutrients (dietary supplements that provide health benefits beyond their nutritional value) in the management of persistent cases of Borrelia burgdorferi [...] Read more.

The primary objective of this paper is to provide an evidence-based update of the literature on the use of bioactive phytochemicals, nutraceuticals, and micronutrients (dietary supplements that provide health benefits beyond their nutritional value) in the management of persistent cases of Borrelia burgdorferi infection (Lyme disease) and two other tick-borne pathogens, Babesia and Bartonella species. Recent studies have advanced our understanding of the pathophysiology and mechanisms of persistent infections. These advances have increasingly enabled clinicians and patients to utilize a wider set of options to manage these frequently disabling conditions. This broader toolkit holds the promise of simultaneously improving treatment outcomes and helping to decrease our reliance on the long-term use of pharmaceutical antimicrobials and antibiotics in the treatment of tick-borne pathogens such as Borrelia burgdorferi, Babesia, and Bartonella. Full article

(This article belongs to the Special Issue Emerging Research on Tick-Borne Pathogens and Diseases)

24 pages, 2483 KiB

Open AccessReview

Rickettsia amblyommatis in Ticks: A Review of Distribution, Pathogenicity, and Diversity

by Elise A. Richardson, R. Michael Roe, Charles S. Apperson and Loganathan Ponnusamy

Microorganisms 2023, 11(2), 493; https://doi.org/10.3390/microorganisms11020493 - 16 Feb 2023

Cited by 7 | Viewed by 2420

Abstract

Rickettsia amblyommatis is a potentially pathogenic species of Rickettsia within the spotted fever group vectored by ticks. While many studies have been published on this species, there is debate over its pathogenicity and the inhibitory role it plays in diagnosing illnesses caused by [...] Read more.

Rickettsia amblyommatis is a potentially pathogenic species of Rickettsia within the spotted fever group vectored by ticks. While many studies have been published on this species, there is debate over its pathogenicity and the inhibitory role it plays in diagnosing illnesses caused by other spotted fever group Rickettsia species. Many publications have recorded the high infection prevalence of R. amblyommatis in tick populations at a global scale. While this species is rather ubiquitous, questions remain over the epidemiological importance of this possible human pathogen. With tick-borne diseases on the rise, understanding the exact role that R. amblyommatis plays as a pathogen and inhibitor of infection relative to other tick-borne pathogens will help public health efforts. The goal of this review was to compile the known literature on R. amblyommatis, review what we know about its geographic distribution, tick vectors, and pathogenicity, assess relatedness between various international strains from ticks by phylogenetic analysis and draw conclusions regarding future research needed. Full article

(This article belongs to the Special Issue Emerging Research on Tick-Borne Pathogens and Diseases)

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