International Journal of Molecular Sciences

Research

Jump to: Review

18 pages, 4024 KiB

Open AccessArticle

Genome-Wide Comparative Analysis of SRCR Gene Superfamily in Invertebrates Reveals Massive and Independent Gene Expansions in the Sponge and Sea Urchin

by Zhangjie Peng, Wei Zhang, Hailun Fu, Yuzhu Li, Chunyu Zhang, Jie Li, Jiulin Chan and Linlin Zhang

Int. J. Mol. Sci. 2024, 25(3), 1515; https://doi.org/10.3390/ijms25031515 - 26 Jan 2024

Viewed by 1275

Abstract

Without general adaptative immunity, invertebrates evolved a vast number of heterogeneous non-self recognition strategies. One of those well-known adaptations is the expansion of the immune receptor gene superfamily coding for scavenger receptor cysteine-rich domain containing proteins (SRCR) in a few invertebrates. Here, we [...] Read more.

Without general adaptative immunity, invertebrates evolved a vast number of heterogeneous non-self recognition strategies. One of those well-known adaptations is the expansion of the immune receptor gene superfamily coding for scavenger receptor cysteine-rich domain containing proteins (SRCR) in a few invertebrates. Here, we investigated the evolutionary history of the SRCR gene superfamily (SRCR-SF) across 29 metazoan species with an emphasis on invertebrates. We analyzed their domain architectures, genome locations and phylogenetic distribution. Our analysis shows extensive genome-wide duplications of the SRCR-SFs in Amphimedon queenslandica and Strongylocentrotus purpuratus. Further molecular evolution study reveals various patterns of conserved cysteines in the sponge and sea urchin SRCR-SFs, indicating independent and convergent evolution of SRCR-SF expansion during invertebrate evolution. In the case of the sponge SRCR-SFs, a novel motif with seven conserved cysteines was identified. Exon–intron structure analysis suggests the rapid evolution of SRCR-SFs during gene duplications in both the sponge and the sea urchin. Our findings across nine representative metazoans also underscore a heightened expression of SRCR-SFs in immune-related tissues, notably the digestive glands. This observation indicates the potential role of SRCR-SFs in reinforcing distinct immune functions in these invertebrates. Collectively, our results reveal that gene duplication, motif structure variation, and exon–intron divergence might lead to the convergent evolution of SRCR-SF expansions in the genomes of the sponge and sea urchin. Our study also suggests that the utilization of SRCR-SF receptor duplication may be a general and basal strategy to increase immune diversity and tissue specificity for the invertebrates. Full article

(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions)

► Show Figures

Figure 1

24 pages, 7450 KiB

Open AccessArticle

Glyceraldehyde 3-Phosphate Dehydrogenase on the Surface of Candida albicans and Nakaseomyces glabratus Cells—A Moonlighting Protein That Binds Human Vitronectin and Plasminogen and Can Adsorb to Pathogenic Fungal Cells via Major Adhesins Als3 and Epa6

by Aneta Bednarek, Dorota Satala, Marcin Zawrotniak, Angela H. Nobbs, Maria Rapala-Kozik and Andrzej Kozik

Int. J. Mol. Sci. 2024, 25(2), 1013; https://doi.org/10.3390/ijms25021013 - 13 Jan 2024

Viewed by 1285

Abstract

Candida albicans and other closely related pathogenic yeast-like fungi carry on their surface numerous loosely adsorbed “moonlighting proteins”—proteins that play evolutionarily conserved intracellular functions but also appear on the cell surface and exhibit additional functions, e.g., contributing to attachment to host tissues. In [...] Read more.

Candida albicans and other closely related pathogenic yeast-like fungi carry on their surface numerous loosely adsorbed “moonlighting proteins”—proteins that play evolutionarily conserved intracellular functions but also appear on the cell surface and exhibit additional functions, e.g., contributing to attachment to host tissues. In the current work, we characterized this “moonlighting” role for glyceraldehyde 3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) of C. albicans and Nakaseomyces glabratus. GAPDH was directly visualized on the cell surface of both species and shown to play a significant part in the total capacity of fungal cells to bind two selected human host proteins—vitronectin and plasminogen. Using purified proteins, both host proteins were found to tightly interact with GAPDH, with dissociation constants in an order of 10⁻⁸ M, as determined by bio-layer interferometry and surface plasmon resonance measurements. It was also shown that exogenous GAPDH tightly adheres to the surface of candidal cells, suggesting that the cell surface location of this moonlighting protein may partly result from the readsorption of its soluble form, which may be present at an infection site (e.g., due to release from dying fungal cells). The major dedicated adhesins, covalently bound to the cell wall—agglutinin-like sequence protein 3 (Als3) and epithelial adhesin 6 (Epa6)—were suggested to serve as the docking platforms for GAPDH in C. albicans and N. glabratus, respectively. Full article

(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions)

► Show Figures

Figure 1

13 pages, 1978 KiB

Open AccessArticle

Wnt3a Facilitates SARS-CoV-2 Pseudovirus Entry into Cells

by Ivonne Melano, Hui-Jye Chen, Loveness Ngwira, Pang-Hung Hsu, Li-Lan Kuo, Lloyd Noriega and Wen-Chi Su

Int. J. Mol. Sci. 2024, 25(1), 217; https://doi.org/10.3390/ijms25010217 - 22 Dec 2023

Viewed by 1053

Abstract

How ACE2 functions as the major host receptor of SARS-CoV-2 despite having low expression in the lungs is still unknown. To facilitate the development of therapeutic strategies against coronaviruses, gaining a deeper comprehension of the molecular mechanism of SARS-CoV-2 infection is imperative. In [...] Read more.

How ACE2 functions as the major host receptor of SARS-CoV-2 despite having low expression in the lungs is still unknown. To facilitate the development of therapeutic strategies against coronaviruses, gaining a deeper comprehension of the molecular mechanism of SARS-CoV-2 infection is imperative. In our previous study, we identified several potential host factors of SARS-CoV-2 using an shRNA arrayed screen, one of which was Wnt3a. Here, we validated the significance of Wnt3a, a potent activator of the Wnt/β-catenin signaling pathway, for SARS-CoV-2 entry into cells by evaluating the effects of its knockdown and overexpression on SARS-CoV-2 pseudotyped virus entry. Further analysis revealed that SARS-CoV-2 pseudotyped virus infection activates the canonical Wnt/β-catenin signaling pathway, which we found could subsequently stimulate ACE2 transcription. Collectively, our study identified Wnt3a as an important host factor that facilitates ACE2-mediated virus infection. Insight into the virus entry mechanism is impactful as it will aid in developing novel therapeutic strategies against current and future coronavirus pandemics. Full article

(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions)

► Show Figures

Figure 1

20 pages, 3403 KiB

Open AccessArticle

Altered Gene Expression of the Parasitoid Pteromalus puparum after Entomopathogenic Fungus Beauveria bassiana Infection

by Lei Yang, Jinting Li, Lei Yang, Xiaofu Wang, Shan Xiao, Shijiao Xiong, Xiaoli Xu, Junfeng Xu and Gongyin Ye

Int. J. Mol. Sci. 2023, 24(23), 17030; https://doi.org/10.3390/ijms242317030 - 1 Dec 2023

Viewed by 939

Abstract

Both parasitoids and entomopathogenic fungi are becoming increasingly crucial for managing pest populations. Therefore, it is essential to carefully consider the potential impact of entomopathogenic fungi on parasitoids due to their widespread pathogenicity and the possible overlap between these biological control tools during [...] Read more.

Both parasitoids and entomopathogenic fungi are becoming increasingly crucial for managing pest populations. Therefore, it is essential to carefully consider the potential impact of entomopathogenic fungi on parasitoids due to their widespread pathogenicity and the possible overlap between these biological control tools during field applications. However, despite their importance, little research has been conducted on the pathogenicity of entomopathogenic fungi on parasitoids. In our study, we aimed to address this knowledge gap by investigating the interaction between the well-known entomopathogenic fungus Beauveria bassiana, and the pupal endoparasitoid Pteromalus puparum. Our results demonstrated that the presence of B. bassiana significantly affected the survival rates of P. puparum under laboratory conditions. The pathogenicity of B. bassiana on P. puparum was dose- and time-dependent, as determined via through surface spraying or oral ingestion. RNA-Seq analysis revealed that the immune system plays a primary and crucial role in defending against B. bassiana. Notably, several upregulated differentially expressed genes (DEGs) involved in the Toll and IMD pathways, which are key components of the insect immune system, and antimicrobial peptides were rapidly induced during both the early and late stages of infection. In contrast, a majority of genes involved in the activation of prophenoloxidase and antioxidant mechanisms were downregulated. Additionally, we identified downregulated DEGs related to cuticle formation, olfactory mechanisms, and detoxification processes. In summary, our study provides valuable insights into the interactions between P. puparum and B. bassiana, shedding light on the changes in gene expression during fungal infection. These findings have significant implications for the development of more effective and sustainable strategies for pest management in agriculture. Full article

(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions)

► Show Figures

Figure 1

16 pages, 7518 KiB

Open AccessArticle

Differential Gene Expression of Malaria Parasite in Response to Red Blood Cell-Specific Glycolytic Intermediate 2,3-Diphosphoglycerate (2,3-DPG)

by Ana Balau, Daniel Sobral, Patrícia Abrantes, Inês Santos, Verónica Mixão, João Paulo Gomes, Sandra Antunes and Ana Paula Arez

Int. J. Mol. Sci. 2023, 24(23), 16869; https://doi.org/10.3390/ijms242316869 - 28 Nov 2023

Viewed by 1109

Abstract

Innovative strategies to control malaria are urgently needed. Exploring the interplay between Plasmodium sp. parasites and host red blood cells (RBCs) offers opportunities for novel antimalarial interventions. Pyruvate kinase deficiency (PKD), characterized by heightened 2,3-diphosphoglycerate (2,3-DPG) concentration, has been associated with protection against [...] Read more.

Innovative strategies to control malaria are urgently needed. Exploring the interplay between Plasmodium sp. parasites and host red blood cells (RBCs) offers opportunities for novel antimalarial interventions. Pyruvate kinase deficiency (PKD), characterized by heightened 2,3-diphosphoglycerate (2,3-DPG) concentration, has been associated with protection against malaria. Elevated levels of 2,3-DPG, a specific mammalian metabolite, may hinder glycolysis, prompting us to hypothesize its potential contribution to PKD-mediated protection. We investigated the impact of the extracellular supplementation of 2,3-DPG on the Plasmodium falciparum intraerythrocytic developmental cycle in vitro. The results showed an inhibition of parasite growth, resulting from significantly fewer progeny from 2,3-DPG-treated parasites. We analyzed differential gene expression and the transcriptomic profile of P. falciparum trophozoites, from in vitro cultures subjected or not subjected to the action of 2,3-DPG, using Nanopore Sequencing Technology. The presence of 2,3-DPG in the culture medium was associated with the significant differential expression of 71 genes, mostly associated with the GO terms nucleic acid binding, transcription or monoatomic anion channel. Further, several genes related to cell cycle control were downregulated in treated parasites. These findings suggest that the presence of this RBC-specific glycolytic metabolite impacts the expression of genes transcribed during the parasite trophozoite stage and the number of merozoites released from individual schizonts, which supports the potential role of 2,3-DPG in the mechanism of protection against malaria by PKD. Full article

(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions)

► Show Figures

Figure 1

16 pages, 3328 KiB

Open AccessArticle

Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model

by Juan Hernández-Goenaga, Julio López-Abán, Adrián Blanco-Gómez, Belén Vicente, Francisco Javier Burguillo, Jesús Pérez-Losada and Antonio Muro

Int. J. Mol. Sci. 2023, 24(19), 14768; https://doi.org/10.3390/ijms241914768 - 30 Sep 2023

Viewed by 976

Abstract

Only a small number of infected people are highly susceptible to schistosomiasis, showing high levels of infection or severe liver fibrosis. The susceptibility to schistosome infection is influenced by genetic background. To assess the genetic basis of susceptibility and identify the chromosomal regions [...] Read more.

Only a small number of infected people are highly susceptible to schistosomiasis, showing high levels of infection or severe liver fibrosis. The susceptibility to schistosome infection is influenced by genetic background. To assess the genetic basis of susceptibility and identify the chromosomal regions involved, a backcross strategy was employed to generate high variation in schistosomiasis susceptibility. This strategy involved crossing the resistant C57BL/6J mouse strain with the susceptible CBA/2J strain. The resulting F1 females (C57BL/6J × CBA/2J) were then backcrossed with CBA/2J males to generate the backcross (BX) cohort. The BX mice exhibited a range of phenotypes, with disease severity varying from mild to severe disease, lacking a fully resistant group. We observed four levels of infection intensity using cluster and principal component analyses and K-means based on parasitological, pathological, and immunological trait measurements. The mice were genotyped with 961 informative SNPs, leading to the identification of 19 new quantitative trait loci (QTL) associated with parasite burden, liver lesions, white blood cell populations, and antibody responses. Two QTLs located on chromosomes 15 and 18 were linked to the number of granulomas, liver lesions, and IgM levels. The corresponding syntenic human regions are located in chromosomes 8 and 18. None of the significant QTLs had been reported previously. Full article

(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions)

► Show Figures

Figure 1

Review

Jump to: Research

19 pages, 1541 KiB

Open AccessReview

Immune Evasion of Mycoplasma gallisepticum: An Overview

by Yang Liu, Yongqiang Wang and Shijun J. Zheng

Int. J. Mol. Sci. 2024, 25(5), 2824; https://doi.org/10.3390/ijms25052824 - 29 Feb 2024

Viewed by 1207

Abstract

Mycoplasma gallisepticum is one of the smallest self-replicating organisms. It causes chronic respiratory disease, leading to significant economic losses in poultry industry. Following M. gallisepticum invasion, the pathogen can persist in the host owing to its immune evasion, resulting in long-term chronic infection. [...] Read more.

Mycoplasma gallisepticum is one of the smallest self-replicating organisms. It causes chronic respiratory disease, leading to significant economic losses in poultry industry. Following M. gallisepticum invasion, the pathogen can persist in the host owing to its immune evasion, resulting in long-term chronic infection. The strategies of immune evasion by mycoplasmas are very complex and recent research has unraveled these sophisticated mechanisms. The antigens of M. gallisepticum exhibit high-frequency changes in size and expression cycle, allowing them to evade the activation of the host humoral immune response. M. gallisepticum can invade non-phagocytic chicken cells and also regulate microRNAs to modulate cell proliferation, inflammation, and apoptosis in tracheal epithelial cells during the disease process. M. gallisepticum has been shown to transiently activate the inflammatory response and then inhibit it by suppressing key inflammatory mediators, avoiding being cleared. The regulation and activation of immune cells are important for host response against mycoplasma infection. However, M. gallisepticum has been shown to interfere with the functions of macrophages and lymphocytes, compromising their defense capabilities. In addition, the pathogen can cause immunological damage to organs by inducing an inflammatory response, cell apoptosis, and oxidative stress, leading to immunosuppression in the host. This review comprehensively summarizes these evasion tactics employed by M. gallisepticum, providing valuable insights into better prevention and control of mycoplasma infection. Full article

(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions)

► Show Figures

Figure 1

24 pages, 1329 KiB

Open AccessReview

Host Subcellular Organelles: Targets of Viral Manipulation

by Min Seok Song, Dong-Kun Lee, Chung-Young Lee, Sang-Cheol Park and Jinsung Yang

Int. J. Mol. Sci. 2024, 25(3), 1638; https://doi.org/10.3390/ijms25031638 - 29 Jan 2024

Viewed by 1614

Abstract

Viruses have evolved sophisticated mechanisms to manipulate host cell processes and utilize intracellular organelles to facilitate their replication. These complex interactions between viruses and cellular organelles allow them to hijack the cellular machinery and impair homeostasis. Moreover, viral infection alters the cell membrane’s [...] Read more.

Viruses have evolved sophisticated mechanisms to manipulate host cell processes and utilize intracellular organelles to facilitate their replication. These complex interactions between viruses and cellular organelles allow them to hijack the cellular machinery and impair homeostasis. Moreover, viral infection alters the cell membrane’s structure and composition and induces vesicle formation to facilitate intracellular trafficking of viral components. However, the research focus has predominantly been on the immune response elicited by viruses, often overlooking the significant alterations that viruses induce in cellular organelles. Gaining a deeper understanding of these virus-induced cellular changes is crucial for elucidating the full life cycle of viruses and developing potent antiviral therapies. Exploring virus-induced cellular changes could substantially improve our understanding of viral infection mechanisms. Full article

(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Molecular Biology of Host and Pathogen Interactions

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI