Pathogens

12 pages, 1583 KiB

Open AccessArticle

The Role of Stratified Cumulative Antibiograms in the (Choice of Appropriate Antibiotics in Urinary Tract Infection) Management of Urinary Tract Infections

by Vaclava Adamkova, Michaela Matouskova, Vanda Gabriela Adamkova, Michal Huptych and Marcela Fontana

Pathogens 2025, 14(2), 141; https://doi.org/10.3390/pathogens14020141 - 3 Feb 2025

Abstract

Urinary tract infections (UTIs) are one of the most common bacterial diseases both in communities and in hospitalized patients, and at the same, time they are one of the most common indications for the use of antibiotics. UTI guidelines are generally available nationally [...] Read more.

Urinary tract infections (UTIs) are one of the most common bacterial diseases both in communities and in hospitalized patients, and at the same, time they are one of the most common indications for the use of antibiotics. UTI guidelines are generally available nationally or internationally, but they do not address all aspects of UTI treatment for different patient cohorts, age, gender, or comorbidities. The aim of the study was to point out the importance of stratified cumulative antibiograms at the level of individual health care facilities and the significant differences between epidemiological data, not only at the national level, but also at the local level. Our study analyses data from 383 patients with UTIs from a hospital department, General University Hospital (GUH), and 272 patients from an outpatient medical facility, Urocentrum (UC). This analysis focuses on the most common UTI causative agent, Escherichia coli, its representation as the causative agent of UTI in patients with complicated acute cystitis (N30), and its representation in complicated acute cystitis in patients with prostate cancer (C61). In addition to the frequency of occurrence, a sub-analysis of the incidence of resistance of E. coli to commonly used antibiotics by age, gender, diagnosis, and medical facility was performed. Results: The most common causative agent of UTI was E. coli. In patients with N30, it was 70% in GUH and 54% in UC, but in oncological patients with UTI, it was only 39% and 35%, respectively. In patients with UTI in C61, there was a significant difference in susceptibility of E. coli between individual health care facilities. Lower resistance was found in UC opposite to GUH isolates in ampicillin, with 29.8% vs. 65%, p = 0.001; amoxicillin/clavulanic acid, with 8.5% vs. 30%, p = 0.01; with 2.1% vs. 17.5% in pivmecillinam, p = 0.01; with 10.6% vs. 37.5% in co-trimoxazole, p = 0.003; and ciprofloxacin, with 10.6% vs. 30%, p = 0.04. The study shows significant differences in the sensitivity of urinary E. coli isolates in patients in relation to age, gender, medical devices, and the presence of comorbidities. Full article

(This article belongs to the Special Issue Hospital-Associated Infections and Antibiotic Resistance)

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27 pages, 734 KiB

Open AccessReview

Oncolytic Viruses in Ovarian Cancer: Where Do We Stand? A Narrative Review

by Fulvio Borella, Marco Carosso, Maria Pia Chiparo, Domenico Ferraioli, Luca Bertero, Niccolò Gallio, Mario Preti, Jessica Cusato, Giorgio Valabrega, Alberto Revelli, Luca Marozio and Stefano Cosma

Pathogens 2025, 14(2), 140; https://doi.org/10.3390/pathogens14020140 - 3 Feb 2025

Abstract

Ovarian cancer (OC) remains the most lethal gynecologic malignancy with limited effective treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic approach for cancer treatment, capable of selectively infecting and lysing cancer cells while stimulating anti-tumor immune responses. Preclinical studies have [...] Read more.

Ovarian cancer (OC) remains the most lethal gynecologic malignancy with limited effective treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic approach for cancer treatment, capable of selectively infecting and lysing cancer cells while stimulating anti-tumor immune responses. Preclinical studies have demonstrated significant tumor regression and prolonged survival in OC models using various OVs, such as herpes simplex. Early-phase clinical trials have shown a favorable safety profile, though the impact on patient survival has been modest. Current research focuses on combining OVs with other treatments like immune checkpoint inhibitors to enhance their efficacy. We provide a comprehensive overview of the current understanding and future directions for utilizing OVs in the management of OC. Full article

(This article belongs to the Section Viral Pathogens)

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9 pages, 1061 KiB

Open AccessArticle

Spatial and Genetic Diversity of Clinical Isolates of Blastocystis in Italy: A Network Analysis

by Isabel Guadano-Procesi, Federica Berrilli and David Di Cave

Pathogens 2025, 14(2), 139; https://doi.org/10.3390/pathogens14020139 - 3 Feb 2025

Abstract

Blastocystis is a common intestinal protist with a global distribution, frequently found in humans and various animals. Despite its prevalence, its role in human health remains debated, oscillating between being a harmless commensal and a potential pathogen. It has also been associated with [...] Read more.

Blastocystis is a common intestinal protist with a global distribution, frequently found in humans and various animals. Despite its prevalence, its role in human health remains debated, oscillating between being a harmless commensal and a potential pathogen. It has also been associated with gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). In Italy, the genetic and spatial diversity of Blastocystis remains understudied, despite the country’s diverse urbanized and environmental landscapes. This study investigates the haplotypic and spatial diversity of clinical isolates of Blastocystis across two different Italian regions, with an emphasis on subtype distribution and genetic variation. Using a network-based haplotype analysis, the study reveals a heterogeneous subtype distribution, with subtype ST4 (47.3%) being the most prevalent, followed by ST3 (20%), ST1 (16.4%), ST2 (12.7%), ST6 (1.8%) and ST7 (1.8%). The overall infection rate detected from symptomatic patients is 9.75%. Notably, ST4 shows limited haplotypic variation, suggesting a more stable population structure that is potentially linked to a human-adapted lineage. In contrast, ST1 and ST2 exhibit greater haplotypic diversity, likely due to ongoing zoonotic transmission. These findings enhance our understanding of the epidemiology of Blastocystis in Italy and underscore the need for further research on its pathogenic potential and transmission dynamics. Full article

(This article belongs to the Section Parasitic Pathogens)

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16 pages, 1268 KiB

Open AccessArticle

Synergistic Antibacterial and Antibiofilm Effects of Clindamycin and Zinc Oxide Nanoparticles Against Pathogenic Oral Bacillus Species

by Maha A. Khalil, Tahany M. Alzaidi, Mohammed Hussein M. Alsharbaty, Sameh S. Ali, Michael Schagerl, Hesham M. Elhariry and Tamer A. Aboshady

Pathogens 2025, 14(2), 138; https://doi.org/10.3390/pathogens14020138 - 2 Feb 2025

Abstract

Oral bacterial pathogens, including Bacillus species, form biofilms that enhance antibiotic resistance, promote bacterial adherence, and maintain structural integrity. The ability of bacteria to form biofilms is directly linked to several oral diseases, including gingivitis, dental caries, periodontitis, periapical periodontitis, and peri-implantitis. These [...] Read more.

Oral bacterial pathogens, including Bacillus species, form biofilms that enhance antibiotic resistance, promote bacterial adherence, and maintain structural integrity. The ability of bacteria to form biofilms is directly linked to several oral diseases, including gingivitis, dental caries, periodontitis, periapical periodontitis, and peri-implantitis. These biofilms act as a predisposing factor for such infections. Nanoparticles, known for their strong antibacterial properties, can target specific biofilm-forming microorganisms without disturbing the normal microflora of the oral cavity. This study focuses on the biofilm-forming ability and clindamycin (CM) resistance of Bacillus species found in the oral cavity. It aims to evaluate the antibacterial and antibiofilm properties of zinc oxide nanoparticles (ZnO-NPs) against oral Bacillus species and assess the effectiveness of combining CM with ZnO-NPs in reducing antibiotic resistance. The antibacterial susceptibility of Bacillus isolates was tested using ZnO-NPs and CM, demonstrating synergistic effects that reduced the minimum inhibitory concentrations by up to 8-fold. The fractional inhibitory concentration (FIC) index indicated a significant synergistic effect in most strains, with FIC values ranging from 0.375 to 0.5. It was found that the majority of Bacillus strains exhibited significant biofilm-forming capabilities, which were reduced when treated with the ZnO-NPs and CM combination. The study also evaluated the cytotoxicity of ZnO-NPs on cancer cells (CAL27) and normal fibroblasts (HFB4). CAL27 cells showed stronger cytotoxicity, with an IC₅₀ of 52.15 µg/mL, compared to HFB4 cells, which had an IC₅₀ of 36.3 µg/mL. Genetic analysis revealed the presence of biofilm-associated genes such as sipW and tasA, along with antibiotic resistance genes (ermC), which correlated with the observed biofilm phenotypes. Overall, this study demonstrates the potential of combining ZnO-NPs with CM to overcome antibiotic resistance and biofilm formation in the oral bacterial pathogens, Bacillus species. These findings suggest new approaches for developing more effective dental treatments targeting oral biofilm-associated infections and antibiotic resistance. Full article

(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)

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23 pages, 3056 KiB

Open AccessArticle

Putrescine Depletion in Leishmania donovani Parasites Causes Immediate Proliferation Arrest Followed by an Apoptosis-like Cell Death

by Julia Johnston, Jonathan Taylor, Surbhi Nahata, Angelica Gatica-Gomez, Yvette L. Anderson, Sophia Kiger, Thong Pham, Kayhan Karimi, Jasmin-Faith Lacar, Nicola S. Carter and Sigrid C. Roberts

Pathogens 2025, 14(2), 137; https://doi.org/10.3390/pathogens14020137 - 2 Feb 2025

Abstract

The polyamine pathway in Leishmania parasites has emerged as a promising target for therapeutic intervention, yet the functions of polyamines in parasites remain largely unexplored. Ornithine decarboxylase (ODC) and spermidine synthase (SPDSYN) catalyze the sequential conversion of ornithine to putrescine and spermidine. We [...] Read more.

The polyamine pathway in Leishmania parasites has emerged as a promising target for therapeutic intervention, yet the functions of polyamines in parasites remain largely unexplored. Ornithine decarboxylase (ODC) and spermidine synthase (SPDSYN) catalyze the sequential conversion of ornithine to putrescine and spermidine. We previously found that Leishmania donovani Δodc and Δspdsyn mutants exhibit markedly reduced growth in vitro and diminished infectivity in mice, with the effect being most pronounced in putrescine-depleted Δodc mutants. Here, we report that, in polyamine-free media, ∆odc mutants arrested proliferation and replication, while ∆spdsyn mutants showed a slow growth and replication phenotype. Starved ∆odc parasites also exhibited a marked reduction in metabolism, which was not observed in the starved ∆spdsyn cells. In contrast, both mutants displayed mitochondrial membrane hyperpolarization. Hallmarks of apoptosis, specifically DNA fragmentation and membrane modifications, were observed in Δodc mutants incubated in polyamine-free media. These results show that putrescine depletion had an immediate detrimental effect on cell growth, replication, and mitochondrial metabolism and caused an apoptosis-like death phenotype. Our findings establish ODC as the most promising therapeutic target within the polyamine biosynthetic pathway for treating leishmaniasis. Full article

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15 pages, 1366 KiB

Open AccessArticle

Biocontrol Potential of Trichoderma spp. Against Phytophthora ramorum

by Elisa Becker, Nirusan Rajakulendran and Simon Francis Shamoun

Pathogens 2025, 14(2), 136; https://doi.org/10.3390/pathogens14020136 - 2 Feb 2025

Abstract

Phytophthora ramorum, the cause of Sudden Oak Death and related diseases, threatens over 130 tree and shrub species. We evaluated the biocontrol potential of isolates from nine Trichoderma species against P. ramorum using growth-rate studies, dual-culture assays, and culture-filtrate assays. Results showed [...] Read more.

Phytophthora ramorum, the cause of Sudden Oak Death and related diseases, threatens over 130 tree and shrub species. We evaluated the biocontrol potential of isolates from nine Trichoderma species against P. ramorum using growth-rate studies, dual-culture assays, and culture-filtrate assays. Results showed significant variation in Trichoderma growth rates and biocontrol potential. Some isolates exhibited rapid growth, effective overgrowth, and lethal effects against P. ramorum and produced potent antagonistic metabolites. Faster growth rates only partially correlated with biocontrol efficacy, indicating that factors beyond growth, such as metabolite production, play significant roles. Notably, isolates of T. koningii, T. viride, and the commercial product SoilGard™ (T. virens) showed promising efficacy. We calculated a combined biocontrol variable to rank isolates based on vigour and efficacy to aid in identifying promising candidates. Our findings support the use of Trichoderma spp. as biocontrol agents against P. ramorum and underscore the need for a multifaceted approach to selecting and optimizing isolates. Our evaluation demonstrated the importance of using different assays to assess specific mechanisms of action of biocontrol candidates. Future research should further explore these interactions to enhance the sustainable management of P. ramorum. Full article

(This article belongs to the Special Issue The Paths of Plant Pathogens—Interactions with Host and Nonhosts and Insight of Mechanisms of Pathogenesis)

14 pages, 698 KiB

Open AccessArticle

Long-Term Surveillance of Food Products of Diverse Origins: A Five-Year Survey of Hepatitis A and Norovirus in Greece, 2019–2024

by Rafail Fokas, Zoi Anastopoulou, Kalypso-Angeliki Koukouvini, Maria-Eleni Dimitrakopoulou, Zoi Kotsiri, Eleftheria Chorti-Tripsa, Chrysoula Kotsalou, Dimosthenis Tzimotoudis and Apostolos Vantarakis

Pathogens 2025, 14(2), 135; https://doi.org/10.3390/pathogens14020135 - 2 Feb 2025

Abstract

This study examines at the prevalence and spread of Hepatitis A Virus (HAV) and norovirus GI/GII in local and imported food products in Greece over a five-year period (2019–2024). A total of two hundred sixty-six food samples were evaluated using obligatory inspections and [...] Read more.

This study examines at the prevalence and spread of Hepatitis A Virus (HAV) and norovirus GI/GII in local and imported food products in Greece over a five-year period (2019–2024). A total of two hundred sixty-six food samples were evaluated using obligatory inspections and virus detection procedures, including 202 for Hepatitis A and 64 for Norovirus. High-risk categories analyzed were vegetables [138 (HAV), 17 (NoV)], fruits [16 (HAV), 7 (NoV)], soft fruits/berries [37 (HAV), 31 (NoV)], processed meals [4 (HAV), 4 (NoV)], and animal-based products [1 (HAV), 5 (NoV)]. Viral RNA was isolated using QIAamp Viral RNA Mini Kit and detected using established RT-qPCR procedures that met ISO requirements for high sensitivity and reproducibility. The results demonstrated HAV contamination mostly in vegetables (4.35% positive rate), with sporadic findings in other categories. Norovirus GI/GII was detected primarily in soft fruits/berries, with a category-specific positive rate of 6.45%. A temporal study revealed that HAV peaks in 2020, while Norovirus contaminations were detected in 2021 and 2024. The findings highlight the important need to incorporate viral testing into routine food safety procedures, especially for high-risk product categories. This study establishes a basic framework for public health initiatives that address gaps in foodborne virus surveillance in Greece. The study’s ramifications extend to global efforts to monitor and reduce foodborne virus contamination, pushing for higher regulatory requirements and targeted preventative actions. Full article

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13 pages, 3282 KiB

Open AccessReview

Merkel Cell Polyomavirus Co-Infection in HIV/AIDS Individuals: Clinical Diagnosis, Consequences and Treatments

by Xianfeng Zhou, Chenxue Yin, Ziqi Lin, Zhangren Yan and Jiangang Wang

Pathogens 2025, 14(2), 134; https://doi.org/10.3390/pathogens14020134 - 2 Feb 2025

Abstract

Merkel cell polyomavirus (MCV) was named for its role as the causative agent of Merkel cell carcinoma (MCC), which is MCV positive in approximately 80% of cases. MCV is classified as a Group 2A carcinogen, which promotes carcinogenesis by integrating T-antigen into the [...] Read more.

Merkel cell polyomavirus (MCV) was named for its role as the causative agent of Merkel cell carcinoma (MCC), which is MCV positive in approximately 80% of cases. MCV is classified as a Group 2A carcinogen, which promotes carcinogenesis by integrating T-antigen into the cell genome. The prevalence of anti-MCV antibodies in the general population can be as high as 90%. MCV typically promotes cancer by integrating T-antigen genes into the host cell genome, and 80% of MCC cases are attributed to MCV activation. In immunocompetent individuals, MCV usually remains latent after infection. However, the incidence of MCC increases significantly in immunocompromised or immunodeficient patients, such as those who have undergone organ transplantation, have chronic lymphocytic leukemia, or are living with human immunodeficiency virus (HIV) infection. Acquired immunodeficiency is a particular feature of people living with HIV. Currently, research on HIV/AIDS patients with MCV infection, clinical outcomes, and treatments is quite limited. This paper reviews previous research and systematically examines the relationship between HIV/AIDS and MCV-associated diseases, with the aim of providing valuable information for the prevention, diagnosis, and treatment of MCV in vulnerable populations. Full article

(This article belongs to the Special Issue The Interplay of Microbiota and Polyomaviruses in Human Health and Disease)

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10 pages, 251 KiB

Open AccessReview

Trypanosoma cruzi Transmission Through Blood Samples and Derivatives: Main Routes, Control Strategies, and Recent Advancements in Blood Banks

by Aline Nefertiti Silva da Gama and Maria de Nazaré Correia Soeiro

Pathogens 2025, 14(2), 133; https://doi.org/10.3390/pathogens14020133 - 2 Feb 2025

Abstract

Neglected Tropical Diseases are a group of 25 conditions caused by diverse agents. They mostly affect people with poorer health outcomes, particularly preventable diseases. The social determinants of health influence the development and progression of these poverty diseases, with inadequate sanitation presenting chronicity, [...] Read more.

Neglected Tropical Diseases are a group of 25 conditions caused by diverse agents. They mostly affect people with poorer health outcomes, particularly preventable diseases. The social determinants of health influence the development and progression of these poverty diseases, with inadequate sanitation presenting chronicity, high morbidity, and economic impacts. Chagas disease, a prominent Neglected Tropical Disease caused by the intracellular pathogen Trypanosoma cruzi, is endemic in Latin America but is increasing as a global concern due to population migration. It is transmitted through insect vectors, congenitally, orally via contaminated food and beverage, via transfusions and organ donation, and due to laboratory accidents, among other minor relevant routes. As a silent illness, with many infected individuals remaining asymptomatic, it contributes to underdiagnosis, and delayed treatment that involves nitro derivatives is often discontinued due to side effects. Chagas disease spreads in non-endemic areas like the United States of America and Europe. Blood screening practices vary, with endemic regions implementing universal testing, while non-endemic areas rely on selective methods. Recent innovations, such as riboflavin–ultraviolet light treatment and arylimidamide compounds, represent promising alternatives to reduce transfusion transmission. This review presents an analysis of Trypanosoma cruzi transmission through blood and derivatives, addressing the main routes, globally implemented control strategies, and recent advancements in blood bank safety. Full article

(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)

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14 pages, 3334 KiB

Open AccessArticle

Dynamic Modulation of IRE1α-XBP1 Signaling by Adenovirus

by Yumi Jang and Fred Bunz

Pathogens 2025, 14(2), 132; https://doi.org/10.3390/pathogens14020132 - 2 Feb 2025

Abstract

The abundant production of foreign proteins and nucleic acids during viral infection elicits a variety of stress responses in host cells. Viral proteins that accumulate in the endoplasmic reticulum (ER) can trigger the unfolded protein response (UPR), a coordinated signaling program that culminates [...] Read more.

The abundant production of foreign proteins and nucleic acids during viral infection elicits a variety of stress responses in host cells. Viral proteins that accumulate in the endoplasmic reticulum (ER) can trigger the unfolded protein response (UPR), a coordinated signaling program that culminates in the expression of downstream genes that collectively restore protein homeostasis. The model pathogen adenovirus serotype 5 (HAdV5) activates the UPR via the signaling axis formed by inositol-requiring enzyme type 1 (IRE1α) and the X-box binding protein 1 (XBP1), a transcription factor required for immune function. Recent studies have suggested that IRE1α-XBP1 activity supports adenovirus replication. Here, we show that HAdV5 exerted opposing effects on IRE1α and XBP1. IRE1α was activated in response to HAdV5, but the production of the XBP1 isoform, XBP1s, was post-transcriptionally blocked. The tumor suppressor p53, which is eliminated by HAdV5 after infection, inhibited IRE1α activation. The de-repression of IRE1α following the degradation of p53 conceivably reflects a novel antiviral mechanism, which HAdV5 ultimately evades by co-opting IRE1α and suppressing XBP1s. Our findings illustrate the opposing mechanisms used by adenoviruses and their host cells to exert control over the UPR, a critical determinant of cell fate. Full article

(This article belongs to the Section Viral Pathogens)

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13 pages, 19888 KiB

Open AccessArticle

Investigating the In Vivo Effects of Anti-Prion Protein Nanobodies on Prion Disease with AAV Vector

by Jingjing Zhang, Mengfei Wang, Dan Wang, Xiangyi Zhang, Yue Ma, Els Pardon, Jan Steyaert, Romany Abskharon, Fei Wang and Jiyan Ma

Pathogens 2025, 14(2), 131; https://doi.org/10.3390/pathogens14020131 - 2 Feb 2025

Abstract

Prion diseases are fatal neurodegenerative disorders affecting humans and animals, and the central pathogenic event is the conversion of normal prion protein (PrP^C) into the pathogenic PrP^Sc isoform. Previous studies have identified nanobodies that specifically recognize PrP^C and inhibit [...] Read more.

Prion diseases are fatal neurodegenerative disorders affecting humans and animals, and the central pathogenic event is the conversion of normal prion protein (PrP^C) into the pathogenic PrP^Sc isoform. Previous studies have identified nanobodies that specifically recognize PrP^C and inhibit the PrP^C to PrP^Sc conversion in vitro. In this study, we investigated the potential for in vivo expression of anti-PrP^C nanobodies and evaluated their impact on prion disease. The coding sequences of three nanobodies were packaged into recombinant adeno-associated virus (rAAV) and were administered via intracerebroventricular (ICV) injection in newborn mice. We found that the expression of these nanobodies remained robust for over 180 days, with no observed detrimental effects. To assess their therapeutic potential, we performed ICV injections of nanobody-expressing rAAVs in newborn mice, followed by intracerebral prion inoculation at 5–6 weeks of age. One nanobody exhibited a small yet statistically significant therapeutic effect, extending survival time from 176 days to 184 days. Analyses of diseased brains revealed that the nanobodies did not alter the pathological changes. Our findings suggest that high levels of anti-PrP^C nanobodies are necessary to delay disease progression. Further optimization of the nanobodies, AAV vectors, or delivery methods is essential to achieve a significant therapeutic effect. Full article

(This article belongs to the Collection Prions and Chronic Wasting Diseases)

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17 pages, 297 KiB

Open AccessReview

Antimicrobial Treatment Options for Multidrug Resistant Gram-Negative Pathogens in Bone and Joint Infections

by Maria Tsilika, Fotinie Ntziora and Efthymia Giannitsioti

Pathogens 2025, 14(2), 130; https://doi.org/10.3390/pathogens14020130 - 1 Feb 2025

Abstract

Multidrug (MDR) and extensive drug (XDR) resistance in Gram-negative bacteria (GNB) emerges worldwide. Although bone and joint infections are mostly caused by Gram-positive bacteria, mainly Staphylococci, MDR GNB substantially increase also as a complication of hospitalization and previous antibiotic administration. This narrative review [...] Read more.

Multidrug (MDR) and extensive drug (XDR) resistance in Gram-negative bacteria (GNB) emerges worldwide. Although bone and joint infections are mostly caused by Gram-positive bacteria, mainly Staphylococci, MDR GNB substantially increase also as a complication of hospitalization and previous antibiotic administration. This narrative review analyzes the epidemiological trend, current experimental data, and clinical experience with available therapeutic options for the difficult to treat (DTR) GNB implicated in bone and joint infections with or without orthopedic implants. The radical debridement and removal of the implant is adequate therapy for most cases, along with prompt and prolonged combined antimicrobial treatment by older and novel antibiotics. Current research and clinical data suggest that fluoroquinolones well penetrate bone tissue and are associated with improved outcomes in DTR GNB; if not available, carbapenems can be used in cases of MDR GNB. For XDR GNB, colistin, fosfomycin, tigecycline, and novel β-lactam/β-lactamase inhibitors can be initiated as combination schemas in intravenous administration, along with local elution from impregnated spacers. However, current data are scarce and large multicenter studies are mandatory in the field. Full article

(This article belongs to the Special Issue Pathogenesis Mechanisms and Antimicrobial Strategies against Multidrug-Resistant Pathogens)

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44 pages, 5316 KiB

Open AccessReview

Harnessing Epigenetics: Innovative Approaches in Diagnosing and Combating Viral Acute Respiratory Infections

by Ankita Saha, Anirban Ganguly, Anoop Kumar, Nityanand Srivastava and Rajiv Pathak

Pathogens 2025, 14(2), 129; https://doi.org/10.3390/pathogens14020129 - 1 Feb 2025

Abstract

Abstract: Acute respiratory infections (ARIs) caused by viruses such as SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV), pose significant global health challenges, particularly for the elderly and immunocompromised individuals. Substantial evidence indicates that acute viral infections can manipulate the host’s epigenome [...] Read more.

Abstract: Acute respiratory infections (ARIs) caused by viruses such as SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV), pose significant global health challenges, particularly for the elderly and immunocompromised individuals. Substantial evidence indicates that acute viral infections can manipulate the host’s epigenome through mechanisms like DNA methylation and histone modifications as part of the immune response. These epigenetic alterations can persist beyond the acute phase, influencing long-term immunity and susceptibility to subsequent infections. Post-infection modulation of the host epigenome may help distinguish infected from uninfected individuals and predict disease severity. Understanding these interactions is crucial for developing effective treatments and preventive strategies for viral ARIs. This review highlights the critical role of epigenetic modifications following viral ARIs in regulating the host’s innate immune defense mechanisms. We discuss the implications of these modifications for diagnosing, preventing, and treating viral infections, contributing to the advancement of precision medicine. Recent studies have identified specific epigenetic changes, such as hypermethylation of interferon-stimulated genes in severe COVID-19 cases, which could serve as biomarkers for early detection and disease progression. Additionally, epigenetic therapies, including inhibitors of DNA methyltransferases and histone deacetylases, show promise in modulating the immune response and improving patient outcomes. Overall, this review provides valuable insights into the epigenetic landscape of viral ARIs, extending beyond traditional genetic perspectives. These insights are essential for advancing diagnostic techniques and developing innovative treatments to address the growing threat of emerging viruses causing ARIs globally. Full article

(This article belongs to the Special Issue The Epidemiology and Diagnosis of Acute Respiratory Infections)

18 pages, 13988 KiB

Open AccessArticle

Comparative Patho-Genomics of Salmonella enterica Serovar Enteritidis Reveal Potential Host-Specific Virulence Factors

by Matthew R. Moreau, Lekshmi K. Edison, Yury V. Ivanov, Dona Saumya S. Wijetunge, Eranda Mangala K. Kurundu Hewage, Jessica E. Linder and Subhashinie Kariyawasam

Pathogens 2025, 14(2), 128; https://doi.org/10.3390/pathogens14020128 - 1 Feb 2025

Abstract

Salmonella enterica serovar Enteritidis (S. Enteritidis) is one of the most common causes of bacterial foodborne infections worldwide. It has an extensive host range, including birds and humans, making it one of the most adaptable Salmonella serovars. This study aims to define [...] Read more.

Salmonella enterica serovar Enteritidis (S. Enteritidis) is one of the most common causes of bacterial foodborne infections worldwide. It has an extensive host range, including birds and humans, making it one of the most adaptable Salmonella serovars. This study aims to define the virulence gene profile of S. Enteritidis and identify genes critical to its host specificity. Currently, there is limited understanding of the molecular mechanisms that allow S. Enteritidis to continue as an important foodborne pathogen. To better understand the genes that may play a role in the host-specific virulence and/or fitness of S. Enteritidis, we first compiled a virulence gene profile-based genome analysis of sequenced S. Enteritidis strains isolated from shell eggs in our laboratory. This analysis was subsequently used to compare the representative genomes of Salmonella serovars with varying host ranges and S. Enteritidis genomes. The study involved a comprehensive and direct examination of the conservation of virulence and/or fitness factors, especially in a host-specific manner—an area that has not been previously explored. Key findings include the identification of 10 virulence-associated clusters of orthologous genes (COGs) specific to poultry-colonizing serovars and 12 virulence-associated COGs unique to human-colonizing serovars. Virulence/fitness-associated gene analysis identified more than 600 genes. The genome sequences of the two S. Enteritidis isolates were compared to those of the other serovars. Genome analysis revealed a core of 2817 COGs that were common to all the Salmonella serovars examined. Comparative genome analysis revealed that 10 virulence-associated COGs were specific to poultry-colonizing serovars, whereas 12 virulence-associated COGs were present in all human-colonizing serovars. Phylogenetic analyses further highlight the evolution of host specificity in S. Enteritidis. This study offers the first comprehensive analysis of genes that may be unique to and possibly essential for the colonization and/or pathogenesis of S. Enteritidis in various and specific hosts. Full article

(This article belongs to the Special Issue Virulence Mechanisms Used by Pathogens Related to Human, Animal, and Environmental Health)

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16 pages, 3907 KiB

Open AccessArticle

Repurposing COVID-19 Compounds (via MMV COVID Box): Almitrine and Bortezomib Induce Programmed Cell Death in Trypanosoma cruzi

by Carlos J. Bethencourt-Estrella, Atteneri López-Arencibia, Jacob Lorenzo-Morales and José E. Piñero

Pathogens 2025, 14(2), 127; https://doi.org/10.3390/pathogens14020127 - 1 Feb 2025

Abstract

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects millions globally, with limited treatment options available. Current therapies, such as benznidazole and nifurtimox, present challenges, including their toxicity, side effects, and inefficacy in the chronic phase. This study explores the potential of [...] Read more.

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects millions globally, with limited treatment options available. Current therapies, such as benznidazole and nifurtimox, present challenges, including their toxicity, side effects, and inefficacy in the chronic phase. This study explores the potential of drug repurposing as a strategy to identify new treatments for T. cruzi, focusing on compounds from the Medicines for Malaria Venture (MMV) COVID Box. An initial screening of 160 compounds identified eight with trypanocidal activity, with almitrine and bortezomib showing the highest efficacy. Both compounds demonstrated significant activity against the epimastigote and amastigote stages of the parasite and showed no cytotoxicity in murine macrophage cells. Key features of programmed cell death (PCD), such as chromatin condensation, mitochondrial membrane potential disruption, and reactive oxygen species accumulation, were observed in T. cruzi treated with these compounds. The potential to induce controlled cell death of these two compounds in T. cruzi suggests they are promising candidates for further research. This study reinforces drug repurposing as a viable approach to discovering novel treatments for neglected tropical diseases like Chagas disease. Full article

(This article belongs to the Special Issue Parasitic Diseases in the Contemporary World)

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12 pages, 258 KiB

Open AccessReview

Novel Strategies for Preventing Fungal Infections—Outline

by Damilola J. Agbadamashi and Claire L. Price

Pathogens 2025, 14(2), 126; https://doi.org/10.3390/pathogens14020126 - 1 Feb 2025

Abstract

Fungal infections are a significant global health challenge, causing approximately 3.8 million deaths annually, with immunocompromised populations particularly at risk. Traditional antifungal therapies, including azoles, echinocandins, and polyenes, face limitations due to rising antifungal resistance, toxicity, and inadequate treatment options. This review explores [...] Read more.

Fungal infections are a significant global health challenge, causing approximately 3.8 million deaths annually, with immunocompromised populations particularly at risk. Traditional antifungal therapies, including azoles, echinocandins, and polyenes, face limitations due to rising antifungal resistance, toxicity, and inadequate treatment options. This review explores innovative strategies for preventing and managing fungal infections, such as vaccines, antifungal peptides, nanotechnology, probiotics, and immunotherapy. Vaccines offer promising avenues for long-term protection, despite difficulties in their development due to fungal complexity and immune evasion mechanisms. Antifungal peptides provide a novel class of agents with broad-spectrum activity and reduced resistance risk, whilst nanotechnology enables targeted, effective drug delivery systems. Probiotics show potential in preventing fungal infections, particularly vulvovaginal candidiasis, by maintaining microbial balance. Immunotherapy leverages immune system modulation to enhance antifungal defenses, and omics technologies deliver comprehensive insights into fungal biology, paving the way for novel therapeutic and vaccine targets. While these approaches hold immense promise, challenges such as cost, accessibility, and translational barriers remain. A coordinated effort among researchers, clinicians, and policymakers is critical to advancing these strategies and addressing the global burden of fungal infections effectively. Full article

(This article belongs to the Section Fungal Pathogens)

8 pages, 389 KiB

Open AccessCase Report

Postoperative Empyema Due to Leclercia adecarboxylata Following Mesothelioma Surgery: A Case Report

by John Fernando Montenegro, Miguel Ángel Diaz-Diaz, Sinthia Vidal-Cañas, Gustavo Urriago, Vanessa Correa, Luis Álvaro Melo-Burbano and Yamil Liscano

Pathogens 2025, 14(2), 125; https://doi.org/10.3390/pathogens14020125 - 30 Jan 2025

Abstract

Background/Objectives: Leclercia adecarboxylata (L. adecarboxylata) is a rare opportunistic pathogen that can cause severe infections like empyema, particularly in immunocompromised individuals. We aim to highlight the importance of the early detection and personalized treatment of L. adecarboxylata infections in patients with [...] Read more.

Background/Objectives: Leclercia adecarboxylata (L. adecarboxylata) is a rare opportunistic pathogen that can cause severe infections like empyema, particularly in immunocompromised individuals. We aim to highlight the importance of the early detection and personalized treatment of L. adecarboxylata infections in patients with comorbidities such as malignant mesothelioma. Methods: We present the case of a 57-year-old man with type 2 diabetes mellitus, hypertension, and malignant mesothelioma who developed a parapneumonic effusion that progressed to empyema. After undergoing pleurectomy and pleurodesis, intraoperative cultures identified L. adecarboxylata. Targeted antibiotic therapy was initiated based on the culture results, and the patient’s response was closely monitored. Results: The patient responded well to targeted antibiotic therapy with ampicillin/sulbactam following the initial empirical treatment with piperacillin/tazobactam. The identification of L. adecarboxylata—a rare finding in empyema cases—was crucial for effective management. The patient recovered fully without complications, highlighting the importance of the early identification and individualized treatment of infections caused by rare pathogens. Conclusions: This case underscores the need to consider L. adecarboxylata in immunocompromised patients presenting with unusual infections. Early detection through advanced diagnostic techniques and personalized antibiotic therapy can improve clinical outcomes and help prevent antimicrobial resistance. Increased clinical awareness and further research into the resistance patterns and treatment approaches for L. adecarboxylata are essential to enhance patient care. Full article

(This article belongs to the Section Bacterial Pathogens)

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13 pages, 271 KiB

Open AccessReview

An Update on Vaccines Against Trypanosoma cruzi and Chagas Disease

by Nisha J. Garg

Pathogens 2025, 14(2), 124; https://doi.org/10.3390/pathogens14020124 - 30 Jan 2025

Abstract

Chagas disease (CD) is a global health concern, with no existing therapies to prophylactically treat adults traveling to endemic countries or those who may already be infected with Trypanosoma cruzi. The economic burden of Chagas cardiomyopathy and heart failure, due to healthcare [...] Read more.

Chagas disease (CD) is a global health concern, with no existing therapies to prophylactically treat adults traveling to endemic countries or those who may already be infected with Trypanosoma cruzi. The economic burden of Chagas cardiomyopathy and heart failure, due to healthcare costs and lost productivity from premature deaths, provides a strong rationale for investment in the development of immune therapies against CD. Vaccine efficacy is proposed to depend heavily on the induction of a robust Th1 response for the clearance of intracellular pathogens like T. cruzi. In this review, updated information on the efforts for vaccine development against CD is provided. Full article

(This article belongs to the Special Issue Chagas Disease: Celebrating the 115th Anniversary of the Discovery of Trypanosoma cruzi)

12 pages, 399 KiB

Open AccessArticle

Effect of Praziquantel Treatment on the Nutritional Status of Children Infected with Schistosoma haematobium

by Louis Fok, Hongying Daisy Dai, David M. Brett-Major, Abebe Animut, Berhanu Erko, John Linville, Yohannes Negash and Abraham Degarege

Pathogens 2025, 14(2), 123; https://doi.org/10.3390/pathogens14020123 - 29 Jan 2025

Abstract

This quasi-experimental trial examined the relationship between Schistosoma haematobium infection and nutritional status, and the impact of single dose praziquantel (PZQ) therapy on undernutrition. A total of 353 children were examined, 112 of which were infected with S. haematobium and treated with PZQ. [...] Read more.

This quasi-experimental trial examined the relationship between Schistosoma haematobium infection and nutritional status, and the impact of single dose praziquantel (PZQ) therapy on undernutrition. A total of 353 children were examined, 112 of which were infected with S. haematobium and treated with PZQ. Children’s heights, weights, and mid-upper arm circumferences (MUAC) were measured at baseline and one month post-treatment. Infected children had significantly smaller mean BMI-for-age z-scores (BAZ) (−1.16 vs. 0.11, p < 0.01) and weight-for-age z-scores (WAZ) (−0.61 vs. −0.31, p = 0.03) than the uninfected ones at baseline. S. haematobium infection was associated with underweight (adjusted OR: 1.76, 95% CI: 1.63–1.90). One month after treatment, BAZ, WAZ, height for age z-scores (HAZ), and MUAC scores were comparable between treated and control children. However, there was a significant decrease in the prevalence of underweight among treated children, while no significant change was observed in the control group one month post-treatment. In conclusion, children infected with S. haematobium are likely to suffer from undernutrition; however, single dose PZQ therapy may not improve their nutritional status within one month of treatment. Future studies could have longer follow-up periods to better estimate the drug’s effect on nutrition. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis and Clinical Management of Human Parasitic Infections)

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