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22 pages, 2998 KiB

Open AccessArticle

Beyond Trypanosoma cruzi: LINE-1 Activation as a Driver of Chronic Inflammation in Chagas Disease

by Marina Dias, Aline Moraes, Tatiana Shiroma, Vitória Pessoa, Antonio Ermoges, Tamires Vital, Luciana Hagström, Davi de Sousa, Márcio de Castro, Bruno Dallago, Izabela Marques Dourado Bastos, Nadjar Nitz and Mariana Hecht

Int. J. Mol. Sci. 2025, 26(10), 4466; https://doi.org/10.3390/ijms26104466 - 8 May 2025

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Abstract

Chagas disease (CD) is endemic in Latin America, with its pathogenesis linked to Trypanosoma cruzi (Tc) persistence and autoimmune responses. This study investigates the role of LINE-1 (L1) activation in inflammation and loss of self-tolerance during Tc infection. In vitro assays evaluated the [...] Read more.

Chagas disease (CD) is endemic in Latin America, with its pathogenesis linked to Trypanosoma cruzi (Tc) persistence and autoimmune responses. This study investigates the role of LINE-1 (L1) activation in inflammation and loss of self-tolerance during Tc infection. In vitro assays evaluated the expression of genes involved in L1 regulation and interferon signaling under basal conditions and following L1 suppression via CRISPR/dCas9. In vivo analyses in a murine model included L1 and IFN expression profiling, autoantibody quantification, and histopathological assessments of liver, spleen, intestine, and heart. Tc infection induced L1 upregulation, correlating with an increased expression of its inhibitors, MOV-10 and APOBEC-3, suggesting host-driven regulatory mechanisms. L1 activation was also associated with the upregulation of DNA repair pathways (MMR and NHEJ) and RNA-sensing pathways (MDA-5 and RIG-I), leading to type I interferon responses. In the murine model, L1 expression was highest in the intestine and heart, independent of parasite burden, and correlated with increased interferon gene expression and autoantibody production. Our findings suggest that CD pathogenesis involves L1-induced chronic inflammation, which may contribute to late-stage symptoms. This highlights self-recognition mechanisms in disease severity and reveals potential therapeutic targets for novel treatments. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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15 pages, 4728 KiB

Open AccessArticle

The Virulence of Metarhizium rileyi to Locusta migratoria Is Determined by the Ability of the Fungus to Respond to Carbon and Nitrogen Sources

by Yunhao Yao, Mei Li, Qingqing Liu, Qiuyue Huang, Shuo Yang, Bin Chen and Yuejin Peng

Int. J. Mol. Sci. 2025, 26(9), 4156; https://doi.org/10.3390/ijms26094156 - 27 Apr 2025

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Abstract

Insects are among the most diverse and abundant organisms on Earth, and their population dynamics are strongly influenced by entomopathogenic fungi. This study examines the role of carbon and nitrogen metabolism in the virulence of the entomopathogenic fungus Metarhizium rileyi against the migratory [...] Read more.

Insects are among the most diverse and abundant organisms on Earth, and their population dynamics are strongly influenced by entomopathogenic fungi. This study examines the role of carbon and nitrogen metabolism in the virulence of the entomopathogenic fungus Metarhizium rileyi against the migratory locust, Locusta migratoria. The findings demonstrate that the capacity of M. rileyi to utilize different carbon and nitrogen sources is a key factor in its virulence. Specifically, two strains of M. rileyi (PPDB201006 and SZCY201010) exhibited distinct metabolic abilities, with PPDB201006 displaying superior growth and enzyme activities on various carbon and nitrogen sources compared to SZCY201010. These metabolic differences were associated with significant variations in virulence, as PPDB201006 induced higher mortality rates in L. migratoria than SZCY201010. Metabolomics analysis revealed that infection by M. rileyi led to substantial alterations in the hemolymph metabolites of L. migratoria, particularly in organic acids, amino acids, sugars, and lipids. These results emphasize the significance of carbon and nitrogen metabolism in the pathogenicity of entomopathogenic fungi and offer new perspectives for optimizing their application as biological control agents. This study not only improves our understanding of fungal virulence mechanisms but also contributes to the development of more effective and sustainable pest management strategies. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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16 pages, 3162 KiB

Open AccessArticle

Long-Term Elite Controllers of HIV-1 Infection Exhibit a Deep Perturbation of Monocyte Homeostasis

by José M. Benito, Daniel Jiménez-Carretero, Jaime Valentín-Quiroga, Ignacio Mahillo, José M. Ligos, Clara Restrepo, Alfonso Cabello, Eduardo López-Collazo, Fátima Sánchez-Cabo, Miguel Górgolas and Norma Rallón

Int. J. Mol. Sci. 2025, 26(9), 3926; https://doi.org/10.3390/ijms26093926 - 22 Apr 2025

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Abstract

Elite controllers (ECs) represent a unique subset of people living with HIV (PLWHs), who can suppress viral replication without requiring antiretroviral therapy (ART). However, despite this viral control, ECs exhibit increased incidences of various comorbid conditions and heightened systemic inflammation, which has been [...] Read more.

Elite controllers (ECs) represent a unique subset of people living with HIV (PLWHs), who can suppress viral replication without requiring antiretroviral therapy (ART). However, despite this viral control, ECs exhibit increased incidences of various comorbid conditions and heightened systemic inflammation, which has been linked to monocyte activation. In this study, we performed an in-depth phenotypic analysis of monocytes in a cohort of long-term ECs (LTECs) and compared them to non-controller patients with ART-mediated control of HIV replication and to non-controller patients with uncontrolled viral replication. A total of 67 participants were included: 22 LTECs, 15 non-controllers on ART (onART), 10 non-controllers without ART (offART), and 20 uninfected controls (UCs) as a reference group. Monocyte phenotypes were analyzed using spectral flow cytometry with a 13-marker panel. The data were analyzed using two approaches: (a) FCS Express software v.7 to define different subsets of monocytes and assess the levels of expression of eight different monocyte functional markers and (b) R software v.4.1.1 for unsupervised multidimensional analysis, including batch correction, dimensionality reduction, and clustering analysis. Monocyte phenotypic profiling was conducted using three different approaches: (1) assessment of monocyte subsets (classical, intermediate, and non-classical monocytes); (2) evaluation of the levels of expression of eight monocyte functional markers, and (3) characterization of monocyte clusters defined through the dimensionality reduction of flow cytometry data (56 different clusters). The monocyte phenotype of the onART group closely resembled that of the UC group. In contrast, LTECs exhibited important alterations in the monocyte phenotype compared to that of the UCs, including (a) an increased proportion of intermediate monocytes and a decreased proportion of classical monocytes (p < 0.01), (b) altered expressions of functional markers across monocyte subsets (p < 0.05), and (c) alterations in sixteen different monocyte clusters (twelve decreased and four increased, p < 0.05). Many of these alterations were also observed when comparing the LTEC and onART groups. Our findings suggest that monocyte-driven mechanisms may contribute to HIV control in LTECs; however, some of these alterations could also promote systemic inflammation and immune activation. These observations provide a compelling rationale for considering therapeutic interventions in this unique population of PLWHs. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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16 pages, 6212 KiB

Open AccessArticle

NK Cells Modulate Dendritic Cell (DC) Signaling Pathways and DC Recruitment in Chlamydial Infection

by Xinting Wang, Chunyan Zhang, Yongci Zhang, Shuhe Wang, Rony Thomas and Xi Yang

Int. J. Mol. Sci. 2025, 26(8), 3769; https://doi.org/10.3390/ijms26083769 - 16 Apr 2025

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Abstract

Previous studies have demonstrated the significant impact of NK cells on adaptive immune responses against chlamydial infections through modulating DCs, yet the molecular mechanisms remain incompletely understood. This study investigates the role of NK cells in modulating DC signaling pathways and the recruitment [...] Read more.

Previous studies have demonstrated the significant impact of NK cells on adaptive immune responses against chlamydial infections through modulating DCs, yet the molecular mechanisms remain incompletely understood. This study investigates the role of NK cells in modulating DC signaling pathways and the recruitment of DCs during Chlamydia muridarum infection. Transcriptomic analyses revealed significant downregulation of key genes in DCs from NK-depleted mice involved in type I immunity, including IL12rb2, IL-18rap, and chemokine signaling components such as Ccl3, Ccl5, and Ccr5. Gene ontology (GO) analyses confirmed impaired chemokine–chemokine receptor interactions in DCs from NK-depleted mice. Moreover, flow cytometry analysis showed that NK-cell depletion reduced CCR5 expression on splenic and pulmonary DCs, impairing their migration toward CCL3 and CCL5. Furthermore, IFN-γ enhanced CCR5 expression on the surface of DCs, consequently promoting their migration, which was blocked by anti-IFN-γ antibodies. In vitro migration assays showed that treatment of DCs with IFN-γ increased their responsiveness to CCL3 and CCL5, the ligands of CCR5. Collectively, this study provides new insights into the indispensable role of NK cells in orchestrating DC signaling and the recruitment of DCs during chlamydial infection. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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12 pages, 3376 KiB

Open AccessArticle

Role of Liver Kinase 1B in Platelet Activation and Host Defense During Klebsiella pneumoniae-Induced Pneumosepsis

by Osoul Chouchane, Valentine Léopold, Christine C. A. van Linge, Alex F. de Vos, Joris J. T. H. Roelofs, Cornelis van ‘t Veer and Tom van der Poll

Int. J. Mol. Sci. 2025, 26(8), 3714; https://doi.org/10.3390/ijms26083714 - 14 Apr 2025

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Abstract

Pneumonia is the most common cause of sepsis, with Klebsiella pneumoniae frequently implicated as a causative pathogen. Platelets play a crucial role in host defense during sepsis, and their activation is essential for effective immune responses, which is at least in part induced [...] Read more.

Pneumonia is the most common cause of sepsis, with Klebsiella pneumoniae frequently implicated as a causative pathogen. Platelets play a crucial role in host defense during sepsis, and their activation is essential for effective immune responses, which is at least in part induced through activation of the collagen receptor glycoprotein (GP)VI. Platelets require energy for their activation, and Liver kinase B1 (LKB1) is a key regulator of energy metabolism. We sought to determine the role of LKB1 in platelet function and host response during K. pneumoniae-induced pneumosepsis. Platelet-specific-Lkb1-deficient mice were generated and compared to control littermates. Platelet counts were unaffected by Lkb1 deficiency in naïve mice. However, Lkb1-deficient platelets exhibited significant hyperreactivity to GPVI stimulation, an effect not observed after stimulation of the thrombin receptor protease-activated receptor 4. During K. pneumoniae infection, platelets of both Lkb1-deficient and control mice became equally hyporesponsive to GPVI stimulation, without differences between genotypes. Platelet-specific Lkb1 deficiency did not alter bacterial outgrowth or dissemination, inflammatory responses, or lung pathology. These findings suggest that while Lkb1 plays a role in regulating platelet activation in response to GPVI stimulation, it does not significantly impact platelet activation or the host response during pneumonia-induced sepsis. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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21 pages, 6143 KiB

Open AccessArticle

Development and Characterization of a Recombinant galT-galU Protein for Broad-Spectrum Immunoprotection Against Porcine Contagious Pleuropneumonia

by Jia-Yong Chen, Yi Deng, Jiale Liu, Xin Wen, Yu-Qin Cao, Yu Mu, Mengke Sun, Chang Miao, Zhiling Peng, Kun Lu, Yu-Luo Wang, Xizhu Chen, Siyu Pang, Dan Wang, Jiayu Zhou, Miaohan Li, Yiping Wen, Rui Wu, Shan Zhao, Yi-Fei Lang, Qi-Gui Yan, Xiaobo Huang, Senyan Du, Yiping Wang, Xinfeng Han, San-Jie Cao and Qin Zhao Show full author list Hide full author list

Int. J. Mol. Sci. 2025, 26(8), 3634; https://doi.org/10.3390/ijms26083634 - 11 Apr 2025

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Abstract

Porcine contagious pleuropneumonia (PCP), caused by Actinobacillus pleuropneumoniae (APP), is a highly contagious disease that leads to significant economic losses in the swine industry. Current vaccines are ineffective due to the presence of multiple serotypes and the absence of a predominant seasonal serotype, [...] Read more.

Porcine contagious pleuropneumonia (PCP), caused by Actinobacillus pleuropneumoniae (APP), is a highly contagious disease that leads to significant economic losses in the swine industry. Current vaccines are ineffective due to the presence of multiple serotypes and the absence of a predominant seasonal serotype, underscoring the need for vaccines with broad-spectrum protection. Previous studies identified galT and galU as promising antigen candidates. In this study, we expressed and characterized a soluble recombinant galT-galU protein (rgalT-galU) from the pET-28a-galT-galU plasmid. The protein, with a molecular weight of 73 kDa, exhibited pronounced immunogenicity in murine models, as indicated by a significant elevation in IgG titers determined through an indirect ELISA. This immune response was further corroborated by substantial antigen-specific splenic lymphocyte proliferation, with a stimulation index of 51.5%. Immunization also resulted in elevated serum cytokines levels of IL-4, IL-12, and IFN-γ, as detected by cytokine assays. Vaccination with rgalT-galU provided immunoprotection against three predominant APP strains (APP1, APP5b, and APP7), achieving protection rates of 71.4%, 71.4%, and 85.7%, respectively. It also effectively mitigated pulmonary lesions and neutrophil infiltration, as verified by histopathological and immunohistochemical analyses. These results indicate that rgalT-galU is a promising candidate for developing cross-protective subunit vaccines against APP infection. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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17 pages, 4309 KiB

Open AccessArticle

The Relationship Between Bacterial Flora in Saliva and Esophageal Mucus and Endoscopic Severity in Patients with Eosinophilic Esophagitis

by Momoyo Sasahira, Hiroshi Matsumoto, Tei Tei Go, Shogen Yo, Shuzo Monden, Takahirao Ninomiya, Motoyasu Oosawa, Osamu Handa, Eiji Umegaki, Ryo Inoue and Akiko Shiotani

Int. J. Mol. Sci. 2025, 26(7), 3026; https://doi.org/10.3390/ijms26073026 - 26 Mar 2025

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Abstract

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and eosinophilic inflammation of the esophageal mucosa. In this study, we investigated the bacterial flora in saliva and esophageal mucus in patients with EoE and examined the relationship between EoE disease [...] Read more.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and eosinophilic inflammation of the esophageal mucosa. In this study, we investigated the bacterial flora in saliva and esophageal mucus in patients with EoE and examined the relationship between EoE disease activity and mucosal cytokine expression, involving patients with active and inactive EoE (A-EoE and I-EoE, respectively). A-EoE was defined as a peak eosinophil count > 15/high-power field, according to the 2025 consensus guidelines. Saliva samples were collected from patients before the endoscopic examination. Brushing samples were collected from the distal esophagus of patients with EoE during endoscopic procedures. The degree of EoE inflammation was assessed using the EoE endoscopic reference score (EREFS). The samples were profiled using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified using tailed PCR. Fifty-nine patients were enrolled, including eight with I-EoE, seventeen with A-EoE, and twenty-eight non-EoE controls. Major bacterial genera such as Streptococcus, Prevotella, Veillonella, and Haemophilus were detected in both the oral cavity and esophagus. Compared with the control group, the active EoE group had significantly more Prevotella spp. in the saliva and esophageal mucosa. Conversely, significantly fewer Neisseria spp. were found in the saliva and Streptococcus spp. in the esophageal mucosa of patients with active EoE. The EREFS of EoE and Streptococcus were inversely correlated. This study elucidated the characteristics of bacterial flora in the saliva and esophageal mucosa of patients with EoE. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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13 pages, 2946 KiB

Open AccessArticle

Transcription Factors Fzc9 and Pdr802 Regulate ATP Levels and Metabolism in Cryptococcus neoformans

by Yuanyuan Ma and Peng Xue

Int. J. Mol. Sci. 2025, 26(5), 1824; https://doi.org/10.3390/ijms26051824 - 20 Feb 2025

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Abstract

Transcription factors Fzc9 and Pdr802, characterized by their Zn₂Cys₆ DNA-binding domain, are essential for the virulence of Cryptococcus neoformans in lung and brain infections. Notably, the in vivo roles of Fzc9 and Pdr802 in contributing to the pathogenicity of C. [...] Read more.

Transcription factors Fzc9 and Pdr802, characterized by their Zn₂Cys₆ DNA-binding domain, are essential for the virulence of Cryptococcus neoformans in lung and brain infections. Notably, the in vivo roles of Fzc9 and Pdr802 in contributing to the pathogenicity of C. neoformans are not adequately reflected by the phenotypic characteristics observed in vitro. This study investigates the effects of gene deletion of FZC9 or PDR802 on the proteomic and metabolomic profiles of C. neoformans. Using mass spectrometry analysis, we identified significant changes in protein abundance and metabolite levels, particularly in pathways related to ATP synthesis. These findings deepen our understanding of the metabolic roles of Fzc9 and Pdr802, suggesting potential targets for the development of novel therapeutic strategies against C. neoformans infections. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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16 pages, 4987 KiB

Open AccessArticle

Characterization of Tetrathionate Hydrolase from Acidothermophilic Sulfur-Oxidizing Archaeon Metallosphaera cuprina Ar-4

by Pei Wang, Liang-Zhi Li, Li-Jun Liu, Ya-Ling Qin, Xiu-Tong Li, Hua-Qun Yin, De-Feng Li, Shuang-Jiang Liu and Cheng-Ying Jiang

Int. J. Mol. Sci. 2025, 26(3), 1338; https://doi.org/10.3390/ijms26031338 - 5 Feb 2025

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Abstract

Tetrathionate hydrolase (TTH) is a key enzyme for the oxidation of reduced inorganic sulfur compounds (RISCs) with the S₄I pathway, which is distributed in autotrophic or facultative autotrophic sulfur-oxidizing bacteria and archaea. In this study, the enzyme TTH_Mc from the [...] Read more.

Tetrathionate hydrolase (TTH) is a key enzyme for the oxidation of reduced inorganic sulfur compounds (RISCs) with the S₄I pathway, which is distributed in autotrophic or facultative autotrophic sulfur-oxidizing bacteria and archaea. In this study, the enzyme TTH_Mc from the acidothermophilic archaeon Metallosphaera cuprina Ar-4^T, encoded by mcup_1281 and belonging to the pyrroloquinoline quinone (PQQ) family, has been shown to possess tetrathionate hydrolysis activity. The molecular mass of the single subunit of TTH_Mc was determined to be 57 kDa. TTH_Mc is proved to be located in the cytoplasm, periplasmic space, and membrane, and the activity of them accounted for 72.3%, 24.0%, and 3.7% of the total activity. Optimal activity was observed at temperatures above 95 °C and pH 6.0, and the kinetic constants K_m and V_max were 0.35 mmol/L and 86.3 μmol/L, respectively. The presence of 0.01 mol/L Mg²⁺ enhances the activity of TTH_Mc, while 0.01 mol/L Ca²⁺ inhibits its activity. The hydrolysis of tetrathionate (TT) by TTH_Mc results in the production of thiosulfate, pentathionate, and hexathionate. This study represents the first description of TTH in the genus Metallosphaera, providing new theoretical insights into the study of sulfur-oxidizing proteins in acidothermophilic archaea. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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26 pages, 7363 KiB

Open AccessArticle

Combinatorial Effects of Cisplatin and PARP Inhibitor Olaparib on Survival, Intestinal Integrity, and Microbiome Modulation in Murine Model

by Mitsuki Matsumura, Hisako Fujihara, Kanna Maita, Moeko Miyakawa, Yushi Sakai, Ryoko Nakayama, Yumi Ito, Mitsuhiko Hasebe, Koji Kawaguchi and Yoshiki Hamada

Int. J. Mol. Sci. 2025, 26(3), 1191; https://doi.org/10.3390/ijms26031191 - 30 Jan 2025

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This study investigated the effects of the poly (ADP-ribose) polymerase (PARP) inhibitor Olaparib, alone and in combination with cisplatin, on intestinal integrity, survival, and microbiome composition using a murine model. Statistical analyses were conducted using one-way analysis of variance with Bonferroni correction for [...] Read more.

This study investigated the effects of the poly (ADP-ribose) polymerase (PARP) inhibitor Olaparib, alone and in combination with cisplatin, on intestinal integrity, survival, and microbiome composition using a murine model. Statistical analyses were conducted using one-way analysis of variance with Bonferroni correction for multiple comparisons, considering p-values of <0.05 as statistically significant. Microbiome profiling was performed using Qiime 2 software. Histopathological and microbiome analyses revealed Olaparib’s protective effects on intestinal integrity, mitigating cisplatin-induced damage. The single administration of cisplatin caused significant histological damage, biochemical disruptions, and dysbiosis, characterized by an increase in pro-inflammatory microbiome, such as Clostridium_sensu_stricto_1, and a decrease in beneficial short-chain fatty acid (SCFA)-producing microbiome. Conversely, the single administration of Olaparib was associated with an increase in SCFA-producing microbiome, such as Lachnospiraceae NK4A136, and exhibited minimal toxicity. The combination administration showed complicated outcomes, as follows: reduced cisplatin-induced cytotoxicity and increased SCFA-producing microbiome ratios, yet the long-term effects revealed reduced survival rates in the cisplatin group and sustained weight gain suppression. These findings emphasize Olaparib’s potential in enhancing intestinal barrier integrity, reducing inflammation, and positively modulating microbiome diversity. However, the entangled pharmacodynamic interactions in the combination administration underscore the need for further investigation. The study highlights the potential of microbiome-targeted interventions in improving therapeutic outcomes for both cancer treatment and inflammatory bowel disease management. Full article

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15 pages, 1906 KiB

Open AccessArticle

Probiotic Spores of Shouchella clausii SF174 and Displayed Bromelain Show Beneficial Additive Potential

by Rowena Corona, Valeria Bontà, Loredana Baccigalupi and Ezio Ricca

Int. J. Mol. Sci. 2025, 26(3), 942; https://doi.org/10.3390/ijms26030942 - 23 Jan 2025

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Abstract

Probiotics have health-beneficial properties mainly due to either a direct action on the host or the modulation of the host microbiota. Health-beneficial properties have also been associated with a variety of plant-derived molecules, widely used as dietary supplements. This study explores the possibility [...] Read more.

Probiotics have health-beneficial properties mainly due to either a direct action on the host or the modulation of the host microbiota. Health-beneficial properties have also been associated with a variety of plant-derived molecules, widely used as dietary supplements. This study explores the possibility of combining the actions of probiotics and of plant-derived molecules by developing beneficial, probiotic-carrying, heterologous molecules. To this extent, spores of SF174, a well-characterized probiotic strain of Shouchella clausii (formerly Bacillus clausii), were used to bind bromelain, a plant-derived mixture of endopeptidases with beneficial effects. Probiotic spores displaying bromelain maintained their antioxidant activity and acquired the endopeptidase activity of the heterologous molecule. The endopeptidase activity was stabilized by the interaction with the spore and largely preserved from degradation at simulated gastric conditions. Under conditions mimicking those encountered in the intestine, as well as upon spore germination, active bromelain was released from the spore surface. The in vitro results reported in this study support the idea that probiotics carrying beneficial heterologous molecules combine the health properties of the probiotic with those of the delivered molecule and pave the way for the development of a novel class of functional probiotics. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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15 pages, 7312 KiB

Open AccessArticle

Genome-Wide Identification and Analysis of Carbohydrate-Binding Modules in Colletotrichum graminicola

by Ya-Fei Wang, Qiu-Li Huang, Xin-Yu Chen, Hong-Lian Li, Jia-Xin Chang, Yu Zhang, Yi-Wen Wang and Yan Shi

Int. J. Mol. Sci. 2025, 26(3), 919; https://doi.org/10.3390/ijms26030919 - 22 Jan 2025

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Abstract

Colletotrichum graminicola is the causative agent of both maize stem rot and leaf blight, which are among the most damaging diseases affecting maize. Carbohydrate-binding modules (CBMs) are protein domains that lack catalytic activity and are commonly found alongside carbohydrate-hydrolyzing enzymes in fungi. A [...] Read more.

Colletotrichum graminicola is the causative agent of both maize stem rot and leaf blight, which are among the most damaging diseases affecting maize. Carbohydrate-binding modules (CBMs) are protein domains that lack catalytic activity and are commonly found alongside carbohydrate-hydrolyzing enzymes in fungi. A comprehensive examination of the C. graminicola TZ-3 genome resulted in the identification of 83 C. graminicola CBM (CgCBM) genes, which are characterized by distinct gene structures and protein motifs. Subcellular localization analysis revealed that the majority of CgCBM proteins were localized in the extracellular space. Investigation of the promoter regions of CgCBM genes uncovered a variety of responsive elements associated with plant hormones, including abscisic acid and methyl jasmonate response elements, as well as various stress-related response elements for drought, cold, defense, and other stress factors. Gene ontology analysis identified the primary functions of CgCBM genes as being linked to polysaccharide metabolism processes. Furthermore, the 83 CgCBM genes exhibited varying responses at different time points during C. graminicola infection, indicating their contribution to the fungus–maize interaction and their potential roles in the fungal pathogenic process. This study provides essential insights into CgCBMs, establishing a crucial foundation for further exploration of their functions in the mechanisms of fungal pathogenicity. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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Review

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28 pages, 5006 KiB

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Positive Regulation of Cellular Proteins by Influenza Virus for Productive Infection

by Jiayu Cong, Ting Wang, Bumsuk Hahm and Chuan Xia

Int. J. Mol. Sci. 2025, 26(8), 3584; https://doi.org/10.3390/ijms26083584 - 10 Apr 2025

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Influenza viruses cause annual epidemics and occasional pandemics through respiratory tract infections, giving rise to substantial morbidity and mortality worldwide. Influenza viruses extensively interact with host cellular proteins and exploit a variety of cellular pathways to accomplish their infection cycle. Some of the [...] Read more.

Influenza viruses cause annual epidemics and occasional pandemics through respiratory tract infections, giving rise to substantial morbidity and mortality worldwide. Influenza viruses extensively interact with host cellular proteins and exploit a variety of cellular pathways to accomplish their infection cycle. Some of the cellular proteins that display negative effects on the virus are degraded by the virus. However, there are also various proteins upregulated by influenza at the expression and/or activation levels. It has been well-established that a large number of host antiviral proteins such as type I interferon-stimulated genes are elevated by viral infection. On the other hand, there are also many cellular proteins that are induced directly by the virus, which are considered as pro-viral factors and often indispensable for rigorous viral propagation or pathogenicity. Here, we review the recent advances in our understanding of the cellular factors deemed to be upregulated and utilized by the influenza virus. The focus is placed on the functions of these pro-viral proteins and the mechanisms associated with promoting viral amplification, evading host immunity, or enhancing viral pathogenicity. Investigating the process of how influenza viruses hijack cellular proteins could provide a framework for inventing the host-factor-targeted drugs to conquer influenza. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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12 pages, 753 KiB

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The Silent Conversation: How Small RNAs Shape Plant–Microbe Relationships

by Jie Liu, Yuntong Lu, Xiaoyan Chen, Xing Liu, Yunying Gu and Fei Li

Int. J. Mol. Sci. 2025, 26(6), 2631; https://doi.org/10.3390/ijms26062631 - 14 Mar 2025

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Abstract

This review highlights the emerging role of cross-kingdom RNA interference in plant–microbe interactions, particularly the transfer of sRNAs from microbes to plants and vice versa, emphasizing the importance of this mechanism in both mutualistic and pathogenic contexts. As plants adapted to terrestrial life, [...] Read more.

This review highlights the emerging role of cross-kingdom RNA interference in plant–microbe interactions, particularly the transfer of sRNAs from microbes to plants and vice versa, emphasizing the importance of this mechanism in both mutualistic and pathogenic contexts. As plants adapted to terrestrial life, they formed symbiotic relationships with microbes, essential for nutrient uptake and defense. Emerging evidence underscores sRNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs), as critical regulators of gene expression and immune responses in plant–microbe interactions. In mutualistic symbioses, such as mycorrhizal fungi and nitrogen-fixing bacteria associations, sRNAs are hypothesized to regulate nutrient exchange and symbiotic stability. In pathogenic scenarios, microbes utilize sRNAs to undermine plant defenses, while plants employ strategies like host-induced gene silencing (HIGS) to counteract these threats. We further explore the emerging role of extracellular vesicles (EVs) in sRNA transport, which is critical for facilitating interspecies communication in both pathogenic and mutualistic contexts. Although the potential of ckRNAi in mutualistic interactions is promising, the review highlights the need for further experimental validation to establish its true significance in these relationships. By synthesizing current research, this review highlights the intricate molecular dialogues mediated by sRNAs in plant–microbe interactions and identifies critical gaps, proposing future research directions aimed at harnessing these mechanisms for agricultural advancements. Full article

(This article belongs to the Special Issue Interactions Between Microbes and Hosts: Physiology, Pathology and Treatment)

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