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Biomarkers for Human and Veterinary Infectious Diseases

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A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Vaccines and Therapeutic Developments".

Deadline for manuscript submissions: closed (25 March 2024) | Viewed by 6540

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Special Issue Editors

Dr. Frank Pessler

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Guest Editor

1. Biomarkers for Infectious Diseases, TWINCORE Center for Experimental and Clinical Infection Research, 30625 Hannover, Germany
2. Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
Interests: biomarkers for infectious diseases and vaccine responses; individualized infection medicine; emphasis on infections of the respiratory tract and the central nervous system; influenza vaccination; molecular profiling of clinical biosamples; functional biomarkers, i.e. markers that provide insights into pathogenesis or suggest treatments
Special Issues, Collections and Topics in MDPI journals

Dr. Leonardo de Araujo

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Guest Editor

Molecular and Experimental Mycobacteriology, Research Center Borstel, 23845 Borstel, Germany
Interests: biomarkers for infectious diseases; respiratory infections, with emphasis on the whole spectrum of tuberculosis (TB) infections; omics studies to identify biomarkers, especially transcriptomics; whole genome and targeted NGS for bacterial drug susceptibility prediction; immunodiagnostic (cellular and molecular immunology)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The field of infectious diseases has rapidly entered the exciting era of individualized medicine, which aims to predict outcomes and select treatments for each individual patient. A prerequisite for this approach is the availability of molecular markers that can aid in defining smaller and smaller subgroups of patients by refining diagnosis of causative pathogens and revealing additional, characteristic features of host responses at the organismal, organ, and cellular level. The advent of high-throughput profiling and sequencing technologies, even at the single cell level, has opened up previously unanticipated possibilities for the discovery of novel biomarkers. For this themed issue on “Biomarkers for Human and Veterinary Infectious Diseases”, jointly sponsored by the sister journals Cells and Pathogens, we welcome submissions that cover both pathogen-derived and patient-derived biomarkers and molecular responses. These can be based on clinical and preclinical investigations, also including cellular models. Submissions reporting advances in diagnostics for specific pathogens should feature the use of a molecular marker. Submissions from human and veterinary infections will be given equal priority. Of course, we hope for lots of novel and innovative findings to create a truly exciting themed issue. Considering that conclusions based on single reports can often not be reproduced in independent studies, we also welcome studies that independently validate (or disprove) previously published findings. Likewise, submissions describing negative findings will be welcome if they test a valid previously defined hypothesis.

Dr. Frank Pessler
Dr. Leonardo de Araujo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

biomarkers
infection
diagnosis
prognosis
prediction
risk assessment

Related Special Issue

Biomarkers for Human and Veterinary Infectious Diseases in Cells (4 articles)

Published Papers (6 papers)

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Research

17 pages, 3043 KiB

Open AccessArticle

Reprogramming of Amino Acid Metabolism Differs between Community-Acquired Pneumonia and Infection-Associated Exacerbation of Chronic Obstructive Pulmonary Disease

by Haroon Arshad, Anastasios Siokis, Raimo Franke, Aamna Habib, Juan Carlos López Alfonso, Yuliya Poliakova, Eva Lücke, Katina Michaelis, Mark Brönstrup, Michael Meyer-Hermann, Ursula Bilitewski, Jordi Vila, Laurent Abel, Thomas Illig, Jens Schreiber and Frank Pessler

Cells 2022, 11(15), 2283; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11152283 - 24 Jul 2022

Cited by 5 | Viewed by 2014

Abstract

Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; compared against healthy controls, n = 33) from presentation to hospital through convalescence. We further aimed to identify biomarkers for acute CAP vs. the clinically potentially similar infection-triggered COPD exacerbation (n = 13). Amino acid metabolism was globally dysregulated in both CAP and COPD. Levels of most amino acids were markedly depressed in acute CAP, and total amino acid concentrations on admission were an accurate biomarker for the differentiation from COPD (AUC = 0.93), as were reduced asparagine and threonine levels (both AUC = 0.92). Reduced tryptophan and histidine levels constituted the most accurate biomarkers for acute CAP vs. controls (AUC = 0.96, 0.94). Only kynurenine, symmetric dimethyl arginine, and phenylalanine levels were increased in acute CAP, and the kynurenine/tryptophan ratio correlated best with clinical recovery and resolution of inflammation. Several amino acids did not reach normal levels by the 6-week follow-up. Glutamate levels were reduced on admission but rose during convalescence to 1.7-fold above levels measured in healthy control. Our data suggest that dysregulated amino acid metabolism in CAP partially persists through clinical recovery and that amino acid metabolism constitutes a source of promising biomarkers for CAP. In particular, total amino acids, asparagine, and threonine may constitute plasma biomarker candidates for the differentiation between CAP and infection-triggered COPD exacerbation and, perhaps, the detection of pneumonia in COPD. Full article

(This article belongs to the Special Issue Biomarkers for Human and Veterinary Infectious Diseases)

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10 pages, 1048 KiB

Open AccessArticle

cfDNA and DNases: New Biomarkers of Sepsis in Preterm Neonates—A Pilot Study

by Moritz Lenz, Thomas Maiberger, Lina Armbrust, Antonia Kiwit, Axel Von der Wense, Konrad Reinshagen, Julia Elrod and Michael Boettcher

Cells 2022, 11(2), 192; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11020192 - 06 Jan 2022

Cited by 8 | Viewed by 2373

Abstract

Introduction: An early and accurate diagnosis of early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) is essential to improve the outcome of this devastating conditions. Especially, preterm infants are at risk. Reliable biomarkers are rare, clinical decision-making depends on clinical appearance and multiple laboratory findings. Markers of NET formation and NET turnover might improve diagnostic precision. Aim of this study was to evaluate the diagnostic value of NETs in sepsis diagnosis in neonatal preterm infants. Methods: Plasma samples of neonatal preterm infants with suspected sepsis were collected. Blood samples were assayed for markers of NET formation and NET turnover: cfDNA, DNase1, nucleosome, NE, and H3Cit. All clinical findings, values of laboratory markers, and epidemiological characteristics were collected retrospectively. Two subpopulations were created to divide EONS from LONS. EMA sepsis criteria for neonatal sepsis were used to generate a sepsis group (EMA positive) and a control group (EMA negative). Results: A total of 31 preterm neonates with suspected sepsis were included. Out of these, nine patients met the criteria for sepsis according to EMA. Regarding early onset neonatal sepsis (3 EONS vs. 10 controls), cfDNA, DNase I, nucleosome, and CRP were elevated significantly. H3Cit and NE did not show any significant elevations. In the late onset sepsis collective (6 LONS vs. 12 controls), cfDNA, DNase I, and CRP differed significantly compared to control group. Full article

(This article belongs to the Special Issue Biomarkers for Human and Veterinary Infectious Diseases)

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17 pages, 1389 KiB

Open AccessArticle

Elevated Levels of IL-33, IL-17 and IL-25 Indicate the Progression from Chronicity to Hepatocellular Carcinoma in Hepatitis C Virus Patients

by Momen Askoura, Hisham A. Abbas, Hadeel Al Sadoun, Wesam H. Abdulaal, Amr S. Abu Lila, Khaled Almansour, Farhan Alshammari, El-Sayed Khafagy, Tarek S. Ibrahim and Wael A. H. Hegazy

Pathogens 2022, 11(1), 57; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11010057 - 03 Jan 2022

Cited by 31 | Viewed by 2444

Abstract

Hepatitis C virus (HCV) is one of the most epidemic viral infections in the world. Three-quarters of individuals infected with HCV become chronic. As a consequence of persistent inflammation, a considerable percentage of chronic patients progress to liver fibrosis, cirrhosis, and finally hepatocellular carcinoma. Cytokines, which are particularly produced from T-helper cells, play a crucial role in immune protection against HCV and the progression of the disease as well. In this study, the role of interleukins IL-33, IL-17, and IL-25 in HCV patients and progression of disease from chronicity to hepatocellular carcinoma will be characterized in order to use them as biomarkers of disease progression. The serum levels of the tested interleukins were measured in patients suffering from chronic hepatitis C (CHC), hepatocellular carcinoma (HCC), and healthy controls (C), and their levels were correlated to the degree of liver fibrosis, liver fibrosis markers and viral load. In contrast to the IL-25 serum level, which increased in patients suffering from HCC only, the serum levels of both IL-33 and IL-17 increased significantly in those patients suffering from CHC and HCC. In addition, IL-33 serum level was found to increase by liver fibrosis progression and viral load, in contrast to both IL-17 and IL-25. Current results indicate a significant role of IL-33 in liver inflammation and fibrosis progress in CHC, whereas IL-17 and IL-25 may be used as biomarkers for the development of hepatocellular carcinoma. Full article

(This article belongs to the Special Issue Biomarkers for Human and Veterinary Infectious Diseases)

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18 pages, 1861 KiB

Open AccessFeature PaperArticle

Transcriptomic Biomarkers for Tuberculosis: Validation of NPC2 as a Single mRNA Biomarker to Diagnose TB, Predict Disease Progression, and Monitor Treatment Response

by Leonardo S. de Araujo, Marcelo Ribeiro-Alves, Matthew F. Wipperman, Charles Kyriakos Vorkas, Frank Pessler and Maria Helena Féres Saad

Cells 2021, 10(10), 2704; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10102704 - 09 Oct 2021

Cited by 3 | Viewed by 2204

Abstract

External validation in different cohorts is a key step in the translational development of new biomarkers. We previously described three host mRNA whose expression in peripheral blood is significantly higher (NPC2) or lower (DOCK9 and EPHA4) in individuals with TB compared to latent TB infection (LTBI) and controls. We have now conducted an independent validation of these genes by re-analyzing publicly available transcriptomic datasets from Brazil, China, Haiti, India, South Africa, and the United Kingdom. Comparisons between TB and control/LTBI showed significant differential expression of all three genes (NPC2^high p < 0.01, DOCK9^low p < 0.01, and EPHA4^low p < 0.05). NPC2^high had the highest mean area under the ROC curve (AUROC) for the differentiation of TB vs. controls (0.95) and LTBI (0.94). In addition, NPC2 accurately distinguished TB from the clinically similar conditions pneumonia (AUROC, 0.88), non-active sarcoidosis (0.87), and lung cancer (0.86), but not from active sarcoidosis (0.66). Interestingly, individuals progressing from LTBI to TB showed a constant increase in NPC2 expression with time when compared to non-progressors (p < 0.05), with a significant change closer to manifestation of active disease (≤3 months, p = 0.003). Moreover, NPC2 expression normalized with completion of anti-TB treatment. Taken together, these results validate NPC2 mRNA as a diagnostic host biomarker for active TB independent of host genetic background. Moreover, they reveal its potential to predict progression from latent to active infection and to indicate a response to anti-TB treatment. Full article

(This article belongs to the Special Issue Biomarkers for Human and Veterinary Infectious Diseases)

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18 pages, 12013 KiB

Open AccessArticle

Complete Genome Sequencing of Leptospira interrogans Isolates from Malaysia Reveals Massive Genome Rearrangement but High Conservation of Virulence-Associated Genes

by Siti Roszilawati Ramli, Boyke Bunk, Cathrin Spröer, Robert Geffers, Michael Jarek, Sabin Bhuju, Marga Goris, Sahlawati Mustakim and Frank Pessler

Pathogens 2021, 10(9), 1198; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091198 - 15 Sep 2021

Cited by 5 | Viewed by 3054

Abstract

The ability of Leptospirae to persist in environments and animal hosts but to cause clinically highly variable disease in humans has made leptospirosis the most common zoonotic disease. Considering the paucity of data on variation in complete genomes of human pathogenic Leptospirae, we have used a combination of Single Molecule Real-Time (SMRT) and Illumina sequencing to obtain complete genome sequences of six human clinical L. interrogans isolates from Malaysia. All six contained the larger (4.28–4.56 Mb) and smaller (0.34–0.395 Mb) chromosome typical of human pathogenic Leptospirae and 0–7 plasmids. Only 24% of the plasmid sequences could be matched to databases. We identified a chromosomal core genome of 3318 coding sequences and strain-specific accessory genomes of 49–179 coding sequences. These sequences enabled detailed genomic strain typing (Genome BLAST Distance Phylogeny, DNA–DNA hybridization, and multi locus sequence typing) and phylogenetic classification (whole-genome SNP genotyping). Even though there was some shared synteny and collinearity across the six genomes, there was evidence of major genome rearrangement, likely driven by horizontal gene transfer and homologous recombination. Mobile genetic elements were identified in all strains in highly varying numbers, including in the rfb locus, which defines serogroups and contributes to immune escape and pathogenesis. On the other hand, there was high conservation of virulence-associated genes including those relating to sialic acid, alginate, and lipid A biosynthesis. These findings suggest (i) that the antigenic variation, adaption to various host environments, and broad spectrum of virulence of L. interrogans are in part due to a high degree of genomic plasticity and (ii) that human pathogenic strains maintain a core set of genes required for virulence. Full article

(This article belongs to the Special Issue Biomarkers for Human and Veterinary Infectious Diseases)

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14 pages, 1532 KiB

Open AccessArticle

Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections

by Amani Al-Mekhlafi, Kurt-Wolfram Sühs, Sven Schuchardt, Maike Kuhn, Kirsten Müller-Vahl, Corinna Trebst, Thomas Skripuletz, Frank Klawonn, Martin Stangel and Frank Pessler

Cells 2021, 10(5), 1115; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10051115 - 06 May 2021

Cited by 9 | Viewed by 3036

Abstract

The identification of CSF biomarkers for bacterial meningitis can potentially improve diagnosis and understanding of pathogenesis, and the differentiation from viral CNS infections is of particular clinical importance. Considering that substantial changes in CSF metabolites in CNS infections have recently been demonstrated, we compared concentrations of 188 metabolites in CSF samples from patients with bacterial meningitis (n = 32), viral meningitis/encephalitis (n = 34), and noninflamed controls (n = 66). Metabolite reprogramming in bacterial meningitis was greatest among phosphatidylcholines, and concentrations of all 54 phosphatidylcholines were significantly (p = 1.2 × 10⁻²⁵–1.5 × 10⁻⁴) higher than in controls. Indeed, all biomarkers for bacterial meningitis vs. viral meningitis/encephalitis with an AUC ≥ 0.86 (ROC curve analysis) were phosphatidylcholines. Four of the five most accurate (AUC ≥ 0.9) phosphatidylcholine biomarkers had higher sensitivity and negative predictive values than CSF lactate or cell count. Concentrations of the 10 most accurate phosphatidylcholine biomarkers were lower in meningitis due to opportunistic pathogens than in meningitis due to typical meningitis pathogens, and they correlated most strongly with parameters reflecting blood–CSF barrier dysfunction and CSF lactate (r = 0.73–0.82), less so with CSF cell count, and not with blood CRP. In contrast to the elevated phosphatidylcholine concentrations in CSF, serum concentrations remained relatively unchanged. Taken together, these results suggest that increased free CSF phosphatidylcholines are sensitive biomarkers for bacterial meningitis and do not merely reflect inflammation but are associated with local disease and a shift in CNS metabolism. Full article

(This article belongs to the Special Issue Biomarkers for Human and Veterinary Infectious Diseases)

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