International Journal of Molecular Sciences

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17 pages, 8001 KiB

Open AccessArticle

Cla4A, a Novel Regulator of Gene Expression Networks Required for Asexual and Insect-Pathogenic Lifecycles of Beauveria bassiana

by Si-Yuan Xu, Rehab Abdelmonem Mohamed, Lei Yu, Sheng-Hua Ying and Ming-Guang Feng

Int. J. Mol. Sci. 2024, 25(12), 6410; https://doi.org/10.3390/ijms25126410 - 10 Jun 2024

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Abstract

Cla4, an orthologous p21-activated kinase crucial for non-entomopathogenic fungal lifestyles, has two paralogs (Cla4A/B) functionally unknown in hypocrealean entomopathogens. Here, we report a regulatory role of Cla4A in gene expression networks of Beauveria bassiana required for asexual and entomopathogenic lifecycles while Cla4B is [...] Read more.

Cla4, an orthologous p21-activated kinase crucial for non-entomopathogenic fungal lifestyles, has two paralogs (Cla4A/B) functionally unknown in hypocrealean entomopathogens. Here, we report a regulatory role of Cla4A in gene expression networks of Beauveria bassiana required for asexual and entomopathogenic lifecycles while Cla4B is functionally redundant. The deletion of cla4A resulted in severe growth defects, reduced stress tolerance, delayed conidiation, altered conidiation mode, impaired conidial quality, and abolished pathogenicity through cuticular penetration, contrasting with no phenotype affected by cla4B deletion. In ∆cla4A, 5288 dysregulated genes were associated with phenotypic defects, which were restored by targeted gene complementation. Among those, 3699 genes were downregulated, including more than 1300 abolished at the transcriptomic level. Hundreds of those downregulated genes were involved in the regulation of transcription, translation, and post-translational modifications and the organization and function of the nuclear chromosome, chromatin, and protein–DNA complex. DNA-binding elements in promoter regions of 130 dysregulated genes were predicted to be targeted by Cla4A domains. Samples of purified Cla4A extract were proven to bind promoter DNAs of 12 predicted genes involved in multiple stress-responsive pathways. Therefore, Cla4A acts as a novel regulator of genomic expression and stability and mediates gene expression networks required for insect-pathogenic fungal adaptations to the host and environment. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 5.0)

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19 pages, 2537 KiB

Open AccessArticle

Evaluating Temperature Effects on Bluetongue Virus Serotype 10 and 17 Coinfection in Culicoides sonorensis

by Molly Carpenter, Jennifer Kopanke, Justin Lee, Case Rodgers, Kirsten Reed, Tyler J. Sherman, Barbara Graham, Lee W. Cohnstaedt, William C. Wilson, Mark Stenglein and Christie Mayo

Int. J. Mol. Sci. 2024, 25(5), 3063; https://doi.org/10.3390/ijms25053063 - 6 Mar 2024

Cited by 1 | Viewed by 1334

Abstract

Bluetongue virus (BTV) is a segmented, double-stranded RNA virus transmitted by Culicoides midges that infects ruminants. As global temperatures increase and geographical ranges of midges expand, there is increased potential for BTV outbreaks from incursions of novel serotypes into endemic regions. However, an [...] Read more.

Bluetongue virus (BTV) is a segmented, double-stranded RNA virus transmitted by Culicoides midges that infects ruminants. As global temperatures increase and geographical ranges of midges expand, there is increased potential for BTV outbreaks from incursions of novel serotypes into endemic regions. However, an understanding of the effect of temperature on reassortment is lacking. The objectives of this study were to compare how temperature affected Culicoides survival, virogenesis, and reassortment in Culicoides sonorensis coinfected with two BTV serotypes. Midges were fed blood meals containing BTV-10, BTV-17, or BTV serotype 10 and 17 and maintained at 20 °C, 25 °C, or 30 °C. Midge survival was assessed, and pools of midges were collected every other day to evaluate virogenesis of BTV via qRT-PCR. Additional pools of coinfected midges were collected for BTV plaque isolation. The genotypes of plaques were determined using next-generation sequencing. Warmer temperatures impacted traits related to vector competence in offsetting ways: BTV replicated faster in midges at warmer temperatures, but midges did not survive as long. Overall, plaques with BTV-17 genotype dominated, but BTV-10 was detected in some plaques, suggesting parental strain fitness may play a role in reassortment outcomes. Temperature adds an important dimension to host–pathogen interactions with implications for transmission and evolution. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 5.0)

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23 pages, 5993 KiB

Open AccessArticle

Lipopolysaccharide of Legionella pneumophila Serogroup 1 Facilitates Interaction with Host Cells

by Bożena Kowalczyk, Markus Petzold, Zbigniew Kaczyński, Agnieszka Szuster-Ciesielska, Rafał Luchowski, Wiesław I. Gruszecki, Beate Fuchs, Christina E. Galuska, Adam Choma, Jacek Tarasiuk and Marta Palusińska-Szysz

Int. J. Mol. Sci. 2023, 24(19), 14602; https://doi.org/10.3390/ijms241914602 - 27 Sep 2023

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Abstract

Legionella pneumophila is the primary causative agent of Legionnaires’ disease. The mutant-type strain interrupted in the ORF7 gene region responsible for the lipopolysaccharide biosynthesis of the L. pneumophila strain Heysham-1, lacking the O-acetyl groups attached to the rhamnose of the core part, [...] Read more.

Legionella pneumophila is the primary causative agent of Legionnaires’ disease. The mutant-type strain interrupted in the ORF7 gene region responsible for the lipopolysaccharide biosynthesis of the L. pneumophila strain Heysham-1, lacking the O-acetyl groups attached to the rhamnose of the core part, showed a higher surface polarity compared with the wild-type strain. The measurement of excitation energy transfer between fluorophores located on the surface of bacteria and eukaryotic cells showed that, at an early stage of interaction with host cells, the mutant exhibited weaker interactions with Acanthamoeba castellanii cells and THP-1-derived macrophages. The mutant displayed reduced adherence to macrophages but enhanced adherence to A. castellanii, suggesting that the O-acetyl group of the LPS core region plays a crucial role in facilitating interaction with macrophages. The lack of core rhamnose O-acetyl groups made it easier for the bacteria to multiply in amoebae and macrophages. The mutant induced TNF-α production more strongly compared with the wild-type strain. The mutant synthesized twice as many ceramides Cer(t34:0) and Cer(t38:0) than the wild-type strain. The study showed that the internal sugars of the LPS core region of L. pneumophila sg 1 can interact with eukaryotic cell surface receptors and mediate in contacting and attaching bacteria to host cells as well as modulating the immune response to infection. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 5.0)

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17 pages, 1726 KiB

Open AccessArticle

For Someone, You Are the Whole World: Host-Specificity of Salmonella enterica

by Anastasiya V. Merkushova, Anton E. Shikov, Anton A. Nizhnikov and Kirill S. Antonets

Int. J. Mol. Sci. 2023, 24(18), 13670; https://doi.org/10.3390/ijms241813670 - 5 Sep 2023

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Abstract

Salmonella enterica is a bacterial pathogen known to cause gastrointestinal infections in diverse hosts, including humans and animals. Despite extensive knowledge of virulence mechanisms, understanding the factors driving host specificity remains limited. In this study, we performed a comprehensive pangenome-wide analysis of S. [...] Read more.

Salmonella enterica is a bacterial pathogen known to cause gastrointestinal infections in diverse hosts, including humans and animals. Despite extensive knowledge of virulence mechanisms, understanding the factors driving host specificity remains limited. In this study, we performed a comprehensive pangenome-wide analysis of S. enterica to identify potential loci determining preference towards certain hosts. We used a dataset of high-quality genome assemblies grouped into 300 reference clusters with a special focus on four host groups: humans, pigs, cattle, and birds. The reconstructed pangenome was shown to be open and enriched with the accessory component implying high genetic diversity. Notably, phylogenetic inferences did not correspond to the distribution of affected hosts, as large compact phylogenetic groups were absent. By performing a pangenome-wide association study, we identified potential host specificity determinants. These included multiple genes encoding proteins involved in distinct infection stages, e.g., secretion systems, surface structures, transporters, transcription regulators, etc. We also identified antibiotic resistance loci in host-adapted strains. Functional annotation corroborated the results obtained with significant enrichments related to stress response, antibiotic resistance, ion transport, and surface or extracellular localization. We suggested categorizing the revealed specificity factors into three main groups: pathogenesis, resistance to antibiotics, and propagation of mobile genetic elements (MGEs). Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 5.0)

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16 pages, 6004 KiB

Open AccessArticle

Naegleria fowleri Extracellular Vesicles Induce Proinflammatory Immune Responses in BV-2 Microglial Cells

by Hương Giang Lê, Jung-Mi Kang, Tuấn Cường Võ, Won Gi Yoo and Byoung-Kuk Na

Int. J. Mol. Sci. 2023, 24(17), 13623; https://doi.org/10.3390/ijms241713623 - 3 Sep 2023

Cited by 5 | Viewed by 2047

Abstract

Extracellular vesicles (EVs) of protozoan parasites have diverse biological functions that are essential for parasite survival and host–parasite interactions. In this study, we characterized the functional properties of EVs from Naegleria fowleri, a pathogenic amoeba that causes a fatal brain infection called [...] Read more.

Extracellular vesicles (EVs) of protozoan parasites have diverse biological functions that are essential for parasite survival and host–parasite interactions. In this study, we characterized the functional properties of EVs from Naegleria fowleri, a pathogenic amoeba that causes a fatal brain infection called primary amoebic meningoencephalitis (PAM). N. fowleri EVs (NfEVs) have been shown to be internalized by host cells such as C6 glial cells and BV-2 microglial cells without causing direct cell death, indicating their potential roles in modulating host cell functions. NfEVs induced increased expression of proinflammatory cytokines and chemokines such as TNF-α, IL-1α, IL-1β, IL-6, IL-17, IFN-γ, MIP-1α, and MIP-2 in BV-2 microglial cells; these increases were initiated via MyD88-dependent TLR-2/TLR-4. The production levels of proinflammatory cytokines and chemokines in NfEVs-stimulated BV-2 microglial cells were effectively downregulated by inhibitors of MAPK, NF-κB, or JAK-STAT. Phosphorylation levels of JNK, p38, ERK, p65, JAK-1, and STAT3 were increased in NfEVs-stimulated BV-2 microglial cells but were effectively suppressed by each corresponding inhibitor. These results suggest that NfEVs could induce proinflammatory immune responses in BV-2 microglial cells via the NF-κB-dependent MAPK and JAK-STAT signaling pathways. Taken together, these findings suggest that NfEVs are pathogenic factors involved in the contact-independent pathogenic mechanisms of N. fowleri by inducing proinflammatory immune responses in BV-2 microglial cells, further contributing to deleterious inflammation in infected foci by activating subsequent inflammation cascades in other brain cells. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 5.0)

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Review

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27 pages, 1586 KiB

Open AccessReview

Characterisation of Lagovirus europaeus GI–RHDVs (Rabbit Haemorrhagic Disease Viruses) in Terms of Their Pathogenicity and Immunogenicity

by Beata Tokarz-Deptuła, Jakub Kulus, Łukasz Baraniecki, Michał Stosik and Wiesław Deptuła

Int. J. Mol. Sci. 2024, 25(10), 5342; https://doi.org/10.3390/ijms25105342 - 14 May 2024

Cited by 2 | Viewed by 1134

Abstract

Rabbit haemorrhagic disease viruses (RHDV) belong to the family Caliciviridae, genus Lagovirus europaeus, genogroup GI, comprising four genotypes GI.1–GI.4, of which the genotypes GI.1 and GI.2 are pathogenic RHD viruses, while the genotypes GI.3 and GI.4 are non-pathogenic RCV (Rabbit calicivirus [...] Read more.

Rabbit haemorrhagic disease viruses (RHDV) belong to the family Caliciviridae, genus Lagovirus europaeus, genogroup GI, comprising four genotypes GI.1–GI.4, of which the genotypes GI.1 and GI.2 are pathogenic RHD viruses, while the genotypes GI.3 and GI.4 are non-pathogenic RCV (Rabbit calicivirus) viruses. Among the pathogenic genotypes GI.1 and GI.2 of RHD viruses, an antigenic variant of RHDV, named RHDVa—now GI.1a–RHDVa, was distinguished in 1996; and in 2010, a variant of RHDV—named RHDVb, later RHDV2 and now GI.2–RHDV2/b—was described; and recombinants of these viruses were registered. Pathogenic viruses of the genotype GI.1 were the cause of a disease described in 1984 in China in domestic (Oryctolagus (O.) cuniculus domesticus) and wild (O. cuniculus) rabbits, characterised by a very rapid course and a mortality rate of 90–100%, which spread in countries all over the world and which has been defined since 1989 as rabbit haemorrhagic disease. It is now accepted that GI.1–RHDV, including GI.1a–RHDVa, cause the predetermined primary haemorrhagic disease in domestic and wild rabbits, while GI.2–RHDV2/b cause it not only in rabbits, including domestic rabbits’ young up to 4 weeks and rabbits immunised with rabbit haemorrhagic disease vaccine, but also in five various species of wild rabbits and seven different species of hares, as well as wild ruminants: mountain muskoxen and European badger. Among these viruses, haemagglutination-positive, doubtful and harmful viruses have been recorded and described and have been shown to form phylogenogroups, immunotypes, haematotypes and pathotypes, which, together with traits that alter and expand their infectious spectrum (rabbit, hare, wild ruminant, badger and various rabbit and hare species), are the determinants of their pathogenicity (infectivity) and immunogenicity and thus shape their virulence. These relationships are the aim of our consideration in this article. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 5.0)

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16 pages, 1477 KiB

Open AccessReview

Interactions of Gram-Positive Bacterial Membrane Vesicles and Hosts: Updates and Future Directions

by Giuseppe Sangiorgio, Emanuele Nicitra, Dalida Bivona, Carmelo Bonomo, Paolo Bonacci, Maria Santagati, Nicolò Musso, Dafne Bongiorno and Stefania Stefani

Int. J. Mol. Sci. 2024, 25(5), 2904; https://doi.org/10.3390/ijms25052904 - 1 Mar 2024

Cited by 2 | Viewed by 1970

Abstract

Extracellular vesicles (EVs) are lipid bilayers derived from cell membranes, released by both eukaryotic cells and bacteria into the extracellular environment. During production, EVs carry proteins, nucleic acids, and various compounds, which are then released. While Gram-positive bacteria were traditionally thought incapable of [...] Read more.

Extracellular vesicles (EVs) are lipid bilayers derived from cell membranes, released by both eukaryotic cells and bacteria into the extracellular environment. During production, EVs carry proteins, nucleic acids, and various compounds, which are then released. While Gram-positive bacteria were traditionally thought incapable of producing EVs due to their thick peptidoglycan cell walls, recent studies on membrane vesicles (MVs) in Gram-positive bacteria have revealed their significant role in bacterial physiology and disease progression. This review explores the current understanding of MVs in Gram-positive bacteria, including the characterization of their content and functions, as well as their interactions with host and bacterial cells. It offers a fresh perspective to enhance our comprehension of Gram-positive bacterial EVs. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 5.0)

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16 pages, 2136 KiB

Open AccessReview

Pharmacomicrobiomics and Drug–Infection Interactions: The Impact of Commensal, Symbiotic and Pathogenic Microorganisms on a Host Response to Drug Therapy

by Norma Torres-Carrillo, Erika Martínez-López, Nora Magdalena Torres-Carrillo, Andres López-Quintero, José Miguel Moreno-Ortiz, Anahí González-Mercado and Itzae Adonai Gutiérrez-Hurtado

Int. J. Mol. Sci. 2023, 24(23), 17100; https://doi.org/10.3390/ijms242317100 - 4 Dec 2023

Cited by 3 | Viewed by 2422

Abstract

Microorganisms have a close relationship with humans, whether it is commensal, symbiotic, or pathogenic. Recently, it has been documented that microorganisms may influence the response to drug therapy. Pharmacomicrobiomics is an emerging field that focuses on the study of how variations in the [...] Read more.

Microorganisms have a close relationship with humans, whether it is commensal, symbiotic, or pathogenic. Recently, it has been documented that microorganisms may influence the response to drug therapy. Pharmacomicrobiomics is an emerging field that focuses on the study of how variations in the microbiome affect the disposition, action, and toxicity of drugs. Two additional sciences have been added to complement pharmacomicrobiomics, namely toxicomicrobiomics, which explores how the microbiome influences drug metabolism and toxicity, and pharmacoecology, which refers to modifications in the microbiome as a result of drug administration. In this context, we introduce the concept of “drug-infection interaction” to describe the influence of pathogenic microorganisms on drug response. This review analyzes the current state of knowledge regarding the relevance of microorganisms in the host’s response to drugs. It also highlights promising areas for future research and proposes the term “drug-infection interaction” as an extension of pharmacomicrobiomics. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 5.0)

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