Pathogens

11 pages, 1414 KiB

Open AccessArticle

Enhancement of ROS Production by Catechin Is a Primary Effect of Increased Azole Efficacy in Nakaseomyces glabratus (Candida glabrata) Cells Lacking the ERG6 Gene

by Nora Tóth Hervay, Daniel Eliaš, Lucia Černáková, Juraj Jacko, Marcela Habová, Natália Chovancová and Yvetta Gbelská

Pathogens 2024, 13(10), 834; https://doi.org/10.3390/pathogens13100834 (registering DOI) - 26 Sep 2024

Abstract

Fungal infections have become an important public health problem. Currently, there are only three available classes of antifungals for the treatment of invasive infections. Two of them, azoles and polyenes, target the synthesis of ergosterol or bind to sterols. A promising strategy to [...] Read more.

Fungal infections have become an important public health problem. Currently, there are only three available classes of antifungals for the treatment of invasive infections. Two of them, azoles and polyenes, target the synthesis of ergosterol or bind to sterols. A promising strategy to improve current therapies is the use of natural compounds in combinational therapies with the existing antifungals. In this work, we analyzed the changes in the susceptibility of the mutant strain of Nakaseomyces glabratus (Candida glabrata) lacking the ERG6 gene (encoding the sterol C-24 methyltransferase in ergosterol biosynthesis) in the presence of catechin and antifungal azoles. The reduced content of ergosterol in the Cgerg6Δ mutant resulted in the increased tolerance of the mutant cells to both azoles and polyenes. The combination of catechin with fluconazole or miconazole led to the growth inhibition of the azole-resistant Cgerg6Δ mutant strain. In the presence of catechin and miconazole, the Cgerg6Δ mutant fails to properly activate the expression of genes encoding the transcription factors CgYap1p and CgMsn4p, as well as the gene expression of CgCTA1, which are involved in oxidative stress response and lead to the intracellular accumulation of ROS. Finally, we show that catechin administration reduces mortality in a Galleria mellonella model infected with C. glabrata. Our work thus supports the use of catechin in combination therapies for fungal infections and shows that the CgERG6 gene could be a potential new drug target. Full article

(This article belongs to the Special Issue Nosocomial Infection and Antimicrobial Resistance)

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25 pages, 4373 KiB

Open AccessArticle

Next Generation Sequencing and Genetic Analyses Reveal Factors Driving Evolution of Sweetpotato Viruses in Uganda

by Joanne Adero, Godfrey Wokorach, Francesca Stomeo, Nasser Yao, Eunice Machuka, Joyce Njuguna, Denis K. Byarugaba, Jan Kreuze, G. Craig Yencho, Milton A. Otema, Benard Yada and Mercy Kitavi

Pathogens 2024, 13(10), 833; https://doi.org/10.3390/pathogens13100833 - 26 Sep 2024

Abstract

Sweetpotato (Ipomoea batatas L.) is an essential food crop globally, especially for farmers facing resource limitations. Like other crops, sweetpotato cultivation faces significant production challenges due to viral infections. This study aimed to identify and characterize viruses affecting sweetpotato crops in Uganda, [...] Read more.

Sweetpotato (Ipomoea batatas L.) is an essential food crop globally, especially for farmers facing resource limitations. Like other crops, sweetpotato cultivation faces significant production challenges due to viral infections. This study aimed to identify and characterize viruses affecting sweetpotato crops in Uganda, mostly those associated with sweetpotato virus disease (SPVD). Infected leaf samples were collected from farmers’ fields in multiple districts spanning three regions in Uganda. MiSeq, a next-generation sequencing platform, was used to generate reads from the viral nucleic acid. The results revealed nine viruses infecting sweetpotato crops in Uganda, with most plants infected by multiple viral species. Sweet potato pakakuy and sweet potato symptomless virus_1 are reported in Uganda for the first time. Phylogenetic analyses demonstrated that some viruses have evolved to form new phylogroups, likely due to high mutations and recombination, particularly in the coat protein, P1 protein, cylindrical inclusion, and helper component proteinase regions of the potyvirus. The sweet potato virus C carried more codons under positive diversifying selection than the closely related sweet potato feathery mottle virus, particularly in the P1 gene. This study provides valuable insights into the viral species infecting sweetpotato crops, infection severity, and the evolution of sweet potato viruses in Uganda. Full article

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14 pages, 3648 KiB

Open AccessReview

Orbital Myositis after Herpes Zoster Ophthalmicus: A Case Report and a Narrative Review of the Literature

by Edoardo Pace, Guido Accardo, Tommaso Lupia, Maria Felice Brizzi, Silvia Corcione and Francesco Giuseppe De Rosa

Pathogens 2024, 13(10), 832; https://doi.org/10.3390/pathogens13100832 - 26 Sep 2024

Abstract

Herpes zoster ophthalmicus results from the reactivation of the latent varicella zoster virus, affecting the first branch of the trigeminal nerve. In 20–70% of cases, Zoster Ophthalmicus can lead to ocular involvement, affecting various orbital structures. Orbital myositis is a rare but severe [...] Read more.

Herpes zoster ophthalmicus results from the reactivation of the latent varicella zoster virus, affecting the first branch of the trigeminal nerve. In 20–70% of cases, Zoster Ophthalmicus can lead to ocular involvement, affecting various orbital structures. Orbital myositis is a rare but severe complication of herpes zoster ophthalmicus. We present a case of a 52-year-old man with no significant medical history who developed zoster-associated right ocular myositis and dacryocystitis. He was treated with intravenous acyclovir and oral steroids. A review of the literature identified 29 patients across 19 studies. The median age was 61 years, with a slight female predominance. In 55% of cases, the patients had no notable medical history. The most common presentation of myositis involved all oculomotor muscles. There were 22 cases who were treated with intravenous antiviral therapy and 19 received steroids. A full resolution of symptoms was achieved in 51.7% of patients. Zoster-related orbital myositis is a rare complication that should be considered even in immunocompetent individuals. It may occur either before or after the appearance of a vesicular rash. Magnetic resonance imaging is the preferred radiological exam for assessing orbital involvement. Intravenous antiviral therapy should be started within 72 h of symptom onset, and its combination with systemic corticosteroids appears to be an effective treatment for zoster-related ocular myositis. Full article

(This article belongs to the Special Issue Herpesvirus Diseases in Humans and Animals)

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11 pages, 2551 KiB

Open AccessArticle

A Novel Jeilongvirus from Florida, USA, Has a Broad Host Cell Tropism Including Human and Non-Human Primate Cells

by Emily DeRuyter, Kuttichantran Subramaniam, Samantha M. Wisely, J. Glenn Morris, Jr. and John A. Lednicky

Pathogens 2024, 13(10), 831; https://doi.org/10.3390/pathogens13100831 - 26 Sep 2024

Abstract

A novel jeilongvirus was identified through next-generation sequencing in cell cultures inoculated with spleen and kidney extracts. The spleen and kidney were obtained from a Peromyscus gossypinus rodent (cotton mouse) found dead in the city of Gainesville, in North-Central Florida, USA. Jeilongviruses are [...] Read more.

A novel jeilongvirus was identified through next-generation sequencing in cell cultures inoculated with spleen and kidney extracts. The spleen and kidney were obtained from a Peromyscus gossypinus rodent (cotton mouse) found dead in the city of Gainesville, in North-Central Florida, USA. Jeilongviruses are paramyxoviruses of the subfamily Orthoparamyxovirinae that have been found in bats, cats, and rodents. We designated the virus we discovered as Gainesville rodent jeilong virus 1 (GRJV1). Preliminary results indicate that GRJV1 can complete its life cycle in various human, non-human primate, and rodent cell lines, suggesting that the virus has a generalist nature with the potential for a spillover event. The early detection of endemic viruses circulating within hosts in North-Central Florida can significantly enhance surveillance efforts, thereby bolstering our ability to monitor and respond to potential outbreaks effectively. Full article

(This article belongs to the Section Viral Pathogens)

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12 pages, 1063 KiB

Open AccessArticle

Identification of New Single Nucleotide Polymorphisms Potentially Related to Small Ruminant Lentivirus Infection Susceptibility in Goats Based on Data Selected from High-Throughput Sequencing

by Magdalena Materniak-Kornas, Katarzyna Ropka-Molik, Katarzyna Piórkowska, Joanna Kowalik, Tomasz Szmatoła, Jacek Sikora, Aldona Kawęcka and Jacek Kuźmak

Pathogens 2024, 13(10), 830; https://doi.org/10.3390/pathogens13100830 - 25 Sep 2024

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Abstract

Small ruminant lentivirus (SRLV) infections are spread in the flocks of sheep and goats all over the world, causing economic loss. Although only a fraction of infected animals develop disease symptoms, all of them may shed the virus, causing uncontrolled spread of the [...] Read more.

Small ruminant lentivirus (SRLV) infections are spread in the flocks of sheep and goats all over the world, causing economic loss. Although only a fraction of infected animals develop disease symptoms, all of them may shed the virus, causing uncontrolled spread of the infection. Antibodies against the virus can be detected in the blood of infected animals and are the main marker of infection. Additionally, in most infected animals, proviral DNA can also be detected, but at different levels. Due to the lack of treatment or vaccines, the most effective strategy to prevent SRLV infections are control programmes introduced by several countries based on the elimination of seropositive individuals from the flock. An alternative approach, which has currently become the rationale, is an identification of host factors which may predispose certain individuals or breeds to resistance or susceptibility to small ruminant lentivirus infection. In our work, attention was paid to goats of the Carpathian breed infected with SRLV. Available RNA-seq results from the blood of 12 goats with a determined level of SRLV proviral load were used to analyse single nucleotide polymorphisms (SNPs) by the variant calling method. Six SNPs within five genes (POU2AF1, BCAT2, TMEM154, PARP14, UBASH3A) were selected for genotyping to determine their association with the level of small ruminant lentivirus proviral DNA in a group of 60 goats. Interestingly, in seronegative individuals, only the TT genotype of the PARP14 gene was observed, while the TMEM154 CC genotype was found only in seropositive goats. Both genes may be considered potential markers for resistance/susceptibility to SRLV infection. In contrast, polymorphisms identified in POU2AF1 and UBASH3A genes seemed to be deleterious for respective protein functions; therefore, these genes are less likely to be recognised as resistance/susceptibility markers of SRLV infection. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Molecular Epidemiology, Diagnostics and Management of Viral Pathogens)

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23 pages, 5143 KiB

Open AccessArticle

Modular Polymerase Synthesis and Internal Protein Domain Swapping via Dual Opposed Frameshifts in the Ebola Virus L Gene

by David B. Stubbs, Jan A. Ruzicka and Ethan W. Taylor

Pathogens 2024, 13(10), 829; https://doi.org/10.3390/pathogens13100829 - 25 Sep 2024

Viewed by 225

Abstract

Sequence analysis of the Zaire ebolavirus (EBOV) polymerase (L gene) mRNA, using online tools, identified a highly ranked −1 programmed ribosomal frameshift (FS) signal including an ideal slippery sequence heptamer (UUUAAAA), with an overlapping coding region featuring two tandem UGA codons, immediately followed [...] Read more.

Sequence analysis of the Zaire ebolavirus (EBOV) polymerase (L gene) mRNA, using online tools, identified a highly ranked −1 programmed ribosomal frameshift (FS) signal including an ideal slippery sequence heptamer (UUUAAAA), with an overlapping coding region featuring two tandem UGA codons, immediately followed by an RNA region that is the inverse complement (antisense) to a region of the mRNA of the selenoprotein iodothyronine deiodinase II (DIO2). This antisense interaction was confirmed in vitro via electrophoretic gel shift assay, using cDNAs at the EBOV and DIO2 segments. The formation of a duplex between the two mRNAs could trigger the ribosomal frameshift, by mimicking the enhancing role of a pseudoknot structure, while providing access to the selenocysteine insertion sequence (SECIS) element contained in the DIO2 mRNA. This process would allow the −1 frame UGA codons to be recoded as selenocysteine, forming part of a C-terminal module in a low abundance truncated isoform of the viral polymerase, potentially functioning in a redox role. Remarkably, 90 bases downstream of the −1 FS site, an active +1 FS site can be demonstrated, which, via a return to the zero frame, would enable the attachment of the entire C-terminal of the polymerase protein. Using a construct with upstream and downstream reporter genes, spanning a wildtype or mutated viral insert, we show significant +1 ribosomal frameshifting at this site. Acting singly or together, frameshifting at these sites (both of which are highly conserved in EBOV strains) could enable the expression of several modified isoforms of the polymerase. The 3D modeling of the predicted EBOV polymerase FS variants using the AI tool, AlphaFold, reveals a peroxiredoxin-like active site with arginine and threonine residues adjacent to a putative UGA-encoded selenocysteine, located on the back of the polymerase “hand”. This module could serve to protect the viral RNA from peroxidative damage. Full article

(This article belongs to the Special Issue New Insights in Viral Diseases and Computational Biology)

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11 pages, 4869 KiB

Open AccessArticle

Long-Lasting, Fine-Tuned Anti-Tumor Activity of Recombinant Listeria monocytogenes Vaccine Is Controlled by Pyroptosis and Necroptosis Regulatory and Effector Molecules

by Abolaji S. Olagunju, Andrew V. D. Sardinha and Gustavo P. Amarante-Mendes

Pathogens 2024, 13(10), 828; https://doi.org/10.3390/pathogens13100828 - 25 Sep 2024

Viewed by 282

Abstract

One of the main objectives of developing new anti-cancer vaccine strategies is to effectively induce CD8+ T cell-mediated anti-tumor immunity. Live recombinant vectors, notably Listeria monocytogenes, have been shown to elicit a robust in vivo CD8+ T-cell response in preclinical settings. Significantly, [...] Read more.

One of the main objectives of developing new anti-cancer vaccine strategies is to effectively induce CD8+ T cell-mediated anti-tumor immunity. Live recombinant vectors, notably Listeria monocytogenes, have been shown to elicit a robust in vivo CD8+ T-cell response in preclinical settings. Significantly, it has been demonstrated that Listeria induces inflammatory/immunogenic cell death mechanisms such as pyroptosis and necroptosis in immune cells that favorably control immunological responses. Therefore, we postulated that the host’s response to Listeria-based vectors and the subsequent induction of CD8+ T cell-mediated immunity would be compromised by the lack of regulatory or effector molecules involved in pyroptosis or necroptosis. To test our hypothesis, we used recombinant L. monocytogenes carrying the ovalbumin gene (LM.OVA) to vaccinate wild-type (WT), caspase-1/11^−/−, gsdmd^−/−, ripk3^−/−, and mlkl^−/− C57Bl/6 mice. We performed an in vivo cytotoxicity assay to assess the efficacy of OVA-specific CD8+ T lymphocytes in eliminating target cells in wild-type and genetically deficient backgrounds. Furthermore, we evaluated the specific anti-tumor immune response in mice inoculated with the B16F0 and B16F0.OVA melanoma cell lines. Our findings demonstrated that while caspase-1/11 and GSDMD deficiencies interfere with the rapid control of LM.OVA infection, neither of the KOs seems to contribute to the early activation of OVA-specific CTL responses. In contrast, the individual deficiency of each one of these proteins positively impacts the generation of long-lasting effector CD8+ T cells. Full article

(This article belongs to the Special Issue Host Immune Responses to Intracellular Pathogens)

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9 pages, 242 KiB

Open AccessArticle

Cytotoxic Activity of Vancomycin-Resistant Enterococci Isolated from Hospitalised Patients

by Ewa Szczuka, Dominika Rolnicka and Maria Wesołowska

Pathogens 2024, 13(10), 827; https://doi.org/10.3390/pathogens13100827 - 25 Sep 2024

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Abstract

Vancomycin-resistant enterococci (VRE) are considered one of the main nosocomial pathogens due to their increasing antibiotic resistance and ability to cause life-threatening infections in humans. This study included VRE isolates obtained from various specimens including urine, blood, faeces, wounds, sputum, and oral cavity [...] Read more.

Vancomycin-resistant enterococci (VRE) are considered one of the main nosocomial pathogens due to their increasing antibiotic resistance and ability to cause life-threatening infections in humans. This study included VRE isolates obtained from various specimens including urine, blood, faeces, wounds, sputum, and oral cavity wash. Of the 37 strains, 30 (81.1%) and 7 (18.9%) were identified by MALDI TOF as Enterococcus faecium and Enterococcus faecalis, respectively. The clinical vancomycin-resistant enterococci exhibited multi-drug resistance (MDR). Apart from vancomycin, the enterococci exhibited resistance to penicillins (89.1 to 100%), fluoroquinolones (100%), rifampicin (86.5%), tetracycline (27%), aminoglycosides (56.8 to 86.5%), quinupristin–dalfopristin (35.1%), and chloramphenicol (10.8%). Moreover, resistance to linezolid and tigecycline emerged among the tested vancomycin-resistant enterococci. The analysis of aminoglycoside modifying enzyme (AME) genes showed the presence of bifunctional aac(6′)-Ie-aph(2″)-Ia genes contributed to high-level aminoglycoside resistance (HLAR) in the E. faecalis and E. faecium isolates. The other AME gene, i.e., aph(3′)-IIIa, was also found in the VRE isolates. All strains carried the vanA gene. Enterococci from colonised gastrointestinal tracts (1/2.7%) and from infection (6/16.2%) showed cytotoxic activity against the human epithelial cell line HEp-2. Full article

(This article belongs to the Special Issue Nosocomial Infection and Antimicrobial Resistance)

21 pages, 6137 KiB

Open AccessArticle

Is Short-Read 16S rRNA Sequencing of Oral Microbiome Sampling a Suitable Diagnostic Tool for Head and Neck Cancer?

by Kenny Yeo, Fangmeinuo Wu, Runhao Li, Eric Smith, Peter-John Wormald, Rowan Valentine, Alkis James Psaltis, Sarah Vreugde and Kevin Fenix

Pathogens 2024, 13(10), 826; https://doi.org/10.3390/pathogens13100826 - 24 Sep 2024

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Abstract

The oral microbiome, studied by sampling the saliva or by oral rinse, has been long thought to have diagnostic capacity for head and neck cancers (HNC). However, previous reports on the HNC oral microbiome provide inconsistent results. The aim of this study is [...] Read more.

The oral microbiome, studied by sampling the saliva or by oral rinse, has been long thought to have diagnostic capacity for head and neck cancers (HNC). However, previous reports on the HNC oral microbiome provide inconsistent results. The aim of this study is to consolidate these datasets and determine the oral microbial composition between HNC patients to healthy and premalignant individuals. We analyzed 16 published head and neck cancer (HNC) short-read 16S rRNA sequencing datasets, specifically targeting the V3V4, V4 and V4V5 regions. These datasets included saliva and oral rinse samples from donors with HNC, as well as from healthy and premalignant donors. Differences in diversities and microbial abundance were determined. HNC saliva displayed lower alpha diversity than healthy donors. In contrast, the opposite trend was observed for oral rinse samples. Beta diversity scores were largely similar across different patient types. Similar oral phyla were detected for all samples, but proportions were largely dependent on sample type (i.e., saliva or oral rinse) and primer set utilized for 16S rRNA sequencing. Neisseria, Leptotrichia and Megasphaera were elevated in healthy saliva, while Mycoplasma was elevated in HNC saliva. Oral rinse and saliva displayed similar enrichment for Fusobacterium, while Veillonella, Alloprevotella, and Campylobacter showed conflicting results. The sparse partial least squares discriminant analysis model performed effectively in discriminating HNC from healthy or premalignant patients using V3V4 saliva (AUC = 0.888) and V3V4 oral rinse (AUC = 0.928), while poor discriminative capacity was observed for V4 saliva (AUC = 0.688). In conclusion, our meta-analysis highlighted the limitations of 16S rRNA sequencing, particularly due to variations across study batches, primer sets (i.e., V3V4, V4), and sample types. Hence, caution should be exercised when interpreting 16S rRNA sequencing results across studies, especially when different primer sets and sample types are used. Full article

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38 pages, 21087 KiB

Open AccessReview

Advances in the Search for SARS-CoV-2 M^pro and PL^pro Inhibitors

by Marcel Arruda Diogo, Augusto Gomes Teixeira Cabral and Renata Barbosa de Oliveira

Pathogens 2024, 13(10), 825; https://doi.org/10.3390/pathogens13100825 - 24 Sep 2024

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Abstract

SARS-CoV-2 is a spherical, positive-sense, single-stranded RNA virus with a large genome, responsible for encoding both structural proteins, vital for the viral particle’s architecture, and non-structural proteins, critical for the virus’s replication cycle. Among the non-structural proteins, two cysteine proteases emerge as promising [...] Read more.

SARS-CoV-2 is a spherical, positive-sense, single-stranded RNA virus with a large genome, responsible for encoding both structural proteins, vital for the viral particle’s architecture, and non-structural proteins, critical for the virus’s replication cycle. Among the non-structural proteins, two cysteine proteases emerge as promising molecular targets for the design of new antiviral compounds. The main protease (M^pro) is a homodimeric enzyme that plays a pivotal role in the formation of the viral replication–transcription complex, associated with the papain-like protease (PL^pro), a cysteine protease that modulates host immune signaling by reversing post-translational modifications of ubiquitin and interferon-stimulated gene 15 (ISG15) in host cells. Due to the importance of these molecular targets for the design and development of novel anti-SARS-CoV-2 drugs, the purpose of this review is to address aspects related to the structure, mechanism of action and strategies for the design of inhibitors capable of targeting the M^pro and PL^pro. Examples of covalent and non-covalent inhibitors that are currently being evaluated in preclinical and clinical studies or already approved for therapy will be also discussed to show the advances in medicinal chemistry in the search for new molecules to treat COVID-19. Full article

(This article belongs to the Special Issue Antiviral and Virucidal Compounds: From Synthesis, to Screening, up to Identification)

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15 pages, 1649 KiB

Open AccessArticle

Toxicity of Common Acaricides, Disinfectants, and Natural Compounds against Eggs of Rhipicephalus annulatus

by Samar M. Ibrahium, Abdel-Azeem S. Abdel-Baki, Sahar M. Gadelhaq, Shawky M. Aboelhadid, Hesham A. Mahran, Saleh Al-Quraishy, Abdulrahman Reyad and Asmaa A. Kamel

Pathogens 2024, 13(10), 824; https://doi.org/10.3390/pathogens13100824 - 24 Sep 2024

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Abstract

Ticks pose a significant threat due to their ability to lay thousands of eggs, which can persist in the environment for extended periods. While the impact of various compounds on adult and larval ticks has been studied, research on their efficacy against tick [...] Read more.

Ticks pose a significant threat due to their ability to lay thousands of eggs, which can persist in the environment for extended periods. While the impact of various compounds on adult and larval ticks has been studied, research on their efficacy against tick eggs is limited. This study evaluated the ovicidal activity of commercial acaricides, disinfectants, and natural products against Rhipicephalus annulatus eggs using the egg hatch assay (EHA). Deltamethrin and cypermethrin caused a non-significant inhibition of hatching (IH%), even at concentrations higher than the recommended levels. By contrast, the acaricides chlorpyrifos, phoxim, and amitraz significantly inhibited hatching at all tested concentrations. Ivermectin also demonstrated significant IH% at various concentrations but did not fully inhibit the hatching process. Among the disinfectants tested, Virkon-S^®, TH4, and Chlorox showed insignificant effects, whereas formalin achieved an IH% of only 34.1% at a high concentration of 200 mg/mL. Natural products, carvacrol and thymol, exhibited significant ovicidal activity, with a significant IH%. In a semi-field application, phoxim (0.5 mg/mL) and deltamethrin (0.05 mg/mL) were sprayed on tick eggs on pasture soil from a farm. The results indicated that phoxim-treated eggs had a 40% IH%, while deltamethrin-treated eggs showed only an 8.79% IH%. In conclusion, the acaricides amitraz, phoxim, and chlorpyrifos, as well as the natural products carvacrol and thymol, caused significant toxicity to R. annulatus eggs. Full article

(This article belongs to the Collection Advances in Tick Research)

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28 pages, 2456 KiB

Open AccessReview

The Ubiquitous Wilt-Inducing Pathogen Fusarium oxysporum—A Review of Genes Studied with Mutant Analysis

by Edan Jackson, Josh Li, Thilini Weerasinghe and Xin Li

Pathogens 2024, 13(10), 823; https://doi.org/10.3390/pathogens13100823 - 24 Sep 2024

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Abstract

Fusarium oxysporum is one of the most economically important plant fungal pathogens, causing devastating Fusarium wilt diseases on a diverse range of hosts, including many key crop plants. Consequently, F. oxysporum has been the subject of extensive research to help develop and improve [...] Read more.

Fusarium oxysporum is one of the most economically important plant fungal pathogens, causing devastating Fusarium wilt diseases on a diverse range of hosts, including many key crop plants. Consequently, F. oxysporum has been the subject of extensive research to help develop and improve crop protection strategies. The sequencing of the F. oxysporum genome 14 years ago has greatly accelerated the discovery and characterization of key genes contributing to F. oxysporum biology and virulence. In this review, we summarize important findings on the molecular mechanisms of F. oxysporum growth, reproduction, and virulence. In particular, we focus on genes studied through mutant analysis, covering genes involved in diverse processes such as metabolism, stress tolerance, sporulation, and pathogenicity, as well as the signaling pathways that regulate them. In doing so, we hope to present a comprehensive review of the molecular understanding of F. oxysporum that will aid the future study of this and related species. 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)

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7 pages, 201 KiB

Open AccessCommunication

Clinical Outcomes and Virulence Factors of Shiga Toxin-Producing Escherichia coli (STEC) from Southern Alberta, Canada, from 2020 to 2022

by Heather Glassman, Vivien Suttorp, Theron White, Kim Ziebell, Ashley Kearney, Kyrylo Bessonov, Vincent Li and Linda Chui

Pathogens 2024, 13(10), 822; https://doi.org/10.3390/pathogens13100822 - 24 Sep 2024

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Abstract

Shiga toxin-producing Escherichia coli (STEC) can cause severe clinical disease in humans, particularly in young children. Recent advances have led to greater availability of sequencing technologies. We sought to use whole genome sequencing data to identify the presence or absence of known virulence [...] Read more.

Shiga toxin-producing Escherichia coli (STEC) can cause severe clinical disease in humans, particularly in young children. Recent advances have led to greater availability of sequencing technologies. We sought to use whole genome sequencing data to identify the presence or absence of known virulence factors in all clinical isolates submitted to our laboratory from Southern Alberta dated 2020–2022 and correlate these virulence factors with clinical outcomes obtained through chart review. Overall, the majority of HUS and hospitalizations were seen in patients with O157:H7 serotypes, and HUS cases were primarily in young children. The frequency of virulence factors differed between O157:H7 and non-O157 serotypes. Within the O157:H7 cases, certain virulence factors, including espP, espX1, and katP, were more frequent in HUS cases. The number of samples was too low to determine statistical significance. Full article

(This article belongs to the Special Issue Advanced Detection and Bioinformatics of Foodborne Pathogens)

10 pages, 1651 KiB

Open AccessArticle

Virus-Specific Nanobody-Chimeras Degrade the Human Cytomegalovirus US28 Protein in CD34+ Cells

by Emma Poole, Janika Schmitt, Stephen C. Graham, Bernard T. Kelly and John Sinclair

Pathogens 2024, 13(10), 821; https://doi.org/10.3390/pathogens13100821 - 24 Sep 2024

Viewed by 492

Abstract

After primary infection, human cytomegalovirus (HCMV) establishes lifelong persistence, underpinned by latent carriage of the virus with spontaneous reactivation events. In the immune-competent, primary infection or reactivation from latency rarely causes disease. However, HCMV can cause significant disease in immune-compromised individuals such as [...] Read more.

After primary infection, human cytomegalovirus (HCMV) establishes lifelong persistence, underpinned by latent carriage of the virus with spontaneous reactivation events. In the immune-competent, primary infection or reactivation from latency rarely causes disease. However, HCMV can cause significant disease in immune-compromised individuals such as immune-suppressed transplant patients. Latency, where the viral genome is carried in the absence of the production of infectious virions, can be established in undifferentiated cells of the myeloid lineage. A number of stimuli can cause virus reactivation from latency to occur, beginning with the induction of viral immediate-early (IE) lytic gene expression. The suppression of viral IE gene expression to establish and maintain latent infection is known to result from a balance of viral and cellular factors. One key viral factor involved in this is the G protein-coupled receptor US28. Recently, we have shown that US28 is targeted for degradation by a modified nanobody (PCTD-Vun100bv) based on the novel PACTAC (PCSK9-antibody clearance-targeting chimeras) approach for targeted protein degradation. Furthermore, we have shown that this PCTD-Vun100bv-induced degradation of US28 results in IE gene expression in experimentally latently infected CD14+ monocytes. However, HCMV also establishes latency in CD34+ bone marrow cells, the progenitors of CD14+ cells. Here, we show that PCTD-Vun100bv also causes US28 degradation in these CD34+ primary cells, again resulting in the induction of viral IE gene expression. Additionally, we show that PCTD-Vun100bv can target US28 in naturally latently infected CD14+ monocytes from an HCMV-seropositive donor, allowing these latently infected cells to be killed by HCMV-specific cytotoxic T cells from that same donor. These observations support the view that targeting US28 for degradation during natural latency could be a tractable ‘shock-and-kill’ strategy to target the latent HCMV reservoir in myeloid cells. Full article

(This article belongs to the Special Issue Understanding Human Cytomegalovirus Pathogenesis: Evidence from the Clinic and Laboratory Models)

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