Microbes and Infection最新文献

{"title":"Chlamydia pneumoniae relies on host glutathione for its growth and induces Integrated stress response-mediated changes in macrophage glutathione metabolism.","authors":"Maarit Ylätalo, Eveliina Taavitsainen-Wahlroos, Inés Reigada, Leena Hanski","doi":"10.1016/j.micinf.2025.105501","DOIUrl":"https://doi.org/10.1016/j.micinf.2025.105501","url":null,"abstract":"<p><p>The obligate intracellular bacterium Chlamydia pneumoniae can enter into persistent phenotype, which is refractory to antibiotics and causes prolonged inflammatory state in the host. Molecular mechanisms enabling C. pneumoniae intracellular survival and governing the balance between persistent and productive infection phenotype remain poorly understood. In this study, the role of glutathione (GSH) metabolism in C. pneumoniae growth and progeny production was studied in THP-1 macrophages and A549 epithelial cells. Results indicate that depletion of cellular GSH pools decreased C. pneumoniae replication, but only if the constituent amino acids were also sequestered from the culture. C. pneumoniae infection increased the expression of GSH biosynthetic genes but also upregulated ChaC1, an intracellular enzyme involved in GSH breakage. C. pneumoniae infection was found to increase PERK phosphorylation in THP-1 macrophages and chemical inhibition of PERK prevented the infection-induced upregulation of GSH biosynthesis and GSH degradation genes and suppressed C. pneumoniae replication. C. pneumoniae -induced ChaC1 upregulation was also suppressed by protein kinase R inhibitor or treatment with ISRIB, indicating an involvement of redundant pathways of the host cell stress response. The data suggest that C. pneumoniae requires amino acids derived from the host cell GSH pools to enable active bacterial replication.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105501"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porcine alveolar macrophages and nasal epithelial cells internalize porcine epidemic diarrhea virus (PEDV) but do not support its replication in vitro.","authors":"Carlos López-Figueroa, Noelia Carmona, Esmeralda Cano, Núria Navarro, Cristina Risco, Joan Repullés, Joaquim Segalés, Júlia Vergara-Alert","doi":"10.1016/j.micinf.2025.105500","DOIUrl":"https://doi.org/10.1016/j.micinf.2025.105500","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV) primarily targets enterocytes subsequent to fecal-oral exposure, resulting in severe gastrointestinal disease in neonatal piglets. However, recent evidence suggests potential alternative PEDV entry and replication routes via the respiratory tract. The present study delved into the possibility of an alternative pathway for PEDV infection in porcine alveolar macrophages (PAMs), 3D4/21 cells (3D4), and nasal turbinate epithelial cells, focusing on the inherent innate antiviral and anti-inflammatory immune responses to a cell-adapted non-S INDEL USA PEDV strain. CCL-81 cells were used as positive controls of infection, while non-infected CCL-81, PAMs, and 3D4 cells served as negative controls. Quantification of the viral load in cells and supernatants (SN) was carried out at multiple hours post-inoculation (hpi; 0, 6, 12, 24, 48, 72, and 96 hpi) using RT-qPCR, while infectious virus titers were assessed through TCID₅₀/ml on cell cultures and immunofluorescence (IF) staining. PEDV capture and internalization were examined using IF at 24 and 48 hpi, alongside the evaluation of the presence of viral particles and ultrastructural changes using transmission electron microscopy (TEM). Proinflammatory and antiviral cytokine levels in SN were measured using ELISA and Luminex. In both PAMs and 3D4 cells, PEDV RNA levels peaked at 12 hpi in cells and SN, then declined gradually without significant differences between cell types. Only few PAMs and 3D4 cells tested positive for PEDV IF, with no increase in positive cells between 24 and 48 hpi. TEM did not reveal viral particles or changes in cell organelles, and no proinflammatory or antiviral cytokine expression was detected in either cell type of macrophage cells. In parallel, nasal turbinate organoids (NTOs), cultivated as 2D monolayer and at an air-liquid interface (ALI), were exposed to PEDV, with RT-qPCR and IF conducted at 24 hpi. Despite the cultivation technique used, similar levels of PEDV RNA were detected in both the cells and the SN, with positive results observed for PEDV IF. Overall, while PAMs, 3D4 cells and nasal epithelium can capture and internalize PEDV, they do not support viral replication or trigger an antiviral or anti-inflammatory responses.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105500"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protection conferred by mucosal novel bivalent Klebsiella pneumoniae vaccine immunization associates with presence of lung CD4⁺ T_RM.","authors":"BiXia Liu, YaRu Gu, YangXue Ou, LuXuan Liu, WenHao Wang, JinRui Zhou, Ying Wang, YeXiang Du, Jing Xie, Yuan Liu, Rui Zhang, QianFei Zuo, Bin Wang","doi":"10.1016/j.micinf.2025.105483","DOIUrl":"10.1016/j.micinf.2025.105483","url":null,"abstract":"<p><p>Klebsiella pneumoniae is the principal cause of hospital-acquired infection with a high morbidity and mortality in immunocompromised individuals, yet no vaccine is approved. Here, we developed a novel bivalent subunit vaccine for the prevention of K. pneumoniae infection based on the outer membrane protein GlnH and the fimbriae protein FimA. The survival rate of immunized mice was significantly increased compared to that of unimmunized mice, while the bacterial burden, weight loss, and lung pathology were drastically reduced. Furthermore, vaccine-elicited CD4⁺ T_RM cells were observed in lung tissues and appeared to play a critical role in vaccine efficacy. Transcriptomic analysis of total lung tissues from mice treated by FTY720 (S1PR1 inhibitor that blocks lymphocyte egress from secondary lymphoid structures) showed that cell activation, cytokine secretion and enhancement of the killing ability of neutrophils were related to the mechanism of protection against K. pneumoniae infection. These findings indicate that GlnH and FimA are effective candidate bivalent vaccine to fight K. pneumoniae infection.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105483"},"PeriodicalIF":2.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM32 positively regulates c-di-GMP-Induced type I interferon signaling pathway in Listeria monocytogenes infection.","authors":"Yaya Pian, Xuan OuYang","doi":"10.1016/j.micinf.2025.105499","DOIUrl":"10.1016/j.micinf.2025.105499","url":null,"abstract":"<p><p>Listeria monocytogenes (Lm) poses a significant threat to human health. TRIM32, an E3 ubiquitin ligase, plays a critical role in regulating immune responses to pathogen infections. Previous studies have shown that TRIM32 deficiency significantly impairs IFN-β production. In this study, we demonstrate that TRIM32 enhances IFN-β release upon activation by cyclic di-GMP (c-di-GMP). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that TRIM32 deficiency upregulates genes associated with metabolic pathways while downregulating those involved in cytokine signaling and inflammatory responses. Western blot analysis further indicated a significant reduction in ERK and JNK phosphorylation in splenocytes and peritoneal macrophages, suggesting that TRIM32 modulates the MAPK signaling pathway. Additionally, the duration of p38, STAT, and TBK1 phosphorylation was shortened in bone marrow-derived macrophages. Collectively, these findings highlight the role of TRIM32 in enhancing the host immune response against Lm infection.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105499"},"PeriodicalIF":2.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-enhanced benzylpenicillin: Bridging antibacterial action with anti-inflammatory potential against antibiotic-resistant bacteria","authors":"Natália Cristina Gomes-da-Silva ,&nbsp;Álefe Roger Silva França ,&nbsp;Clenilton Costa dos Santos ,&nbsp;Luciana Magalhães Rebelo Alencar ,&nbsp;Elaine Cruz Rosas ,&nbsp;Luana Barbosa Corrêa ,&nbsp;Carolline M.A. Lorentino ,&nbsp;André L.S. Santos ,&nbsp;Eduardo Ricci-Junior ,&nbsp;Ralph Santos-Oliveira","doi":"10.1016/j.micinf.2024.105436","DOIUrl":"10.1016/j.micinf.2024.105436","url":null,"abstract":"<div><div>This study investigates the enhancement of benzylpenicillin's antibacterial properties using nanomedicine, specifically by developing benzylpenicillin nanoemulsions. To address the escalating issue of bacterial resistance, we employed the advanced techniques Raman spectroscopy and atomic force microscopy to analyze the nanoemulsions' molecular structure and characteristics. We then evaluated the impact of these nanoemulsions on nitric oxide production by macrophages to deternine their potential to modulate inflammatory responses. We further assessed the antibacterial effectiveness of the nanoparticles against the pathogens <em>Streptococcus pyogenes</em> (Group A <em>Streptococcus</em>) and <em>Streptococcus agalactiae</em> (Group B <em>Streptococcus</em>). The results of antibiograms showed significant efficacy against Gram-positive bacteria, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, confirming their bactericidal potential. The investigation into the mechanism of action suggested substantial disruption to bacterial membrane integrity, underscoring a possible mode of antibacterial activity. Overall, the study provides valuable insights into the synergistic relationship between antibiotics and nanoparticles. In particular, it demonstrates the potential of benzylpenicillin nanoparticles to enhance the antimicrobial efficacy and influence inflammatory responses obtained by evaluating nitrite, IL-6 and TNF-α, offering promising avenues for future clinical applications and strategies to combat bacterial resistance.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105436"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photodynamic therapy reduces viability, enhances itraconazole activity, and impairs mitochondrial physiology of Sporothrix brasiliensis","authors":"Mariana Lucy Mesquita Ramos ,&nbsp;Azuil Barrinha ,&nbsp;Glauber Ribeiro de Sousa Araújo ,&nbsp;Vinicius Alves ,&nbsp;Iara Bastos de Andrade ,&nbsp;Dario Corrêa-Junior ,&nbsp;Maria Cristina Machado Motta ,&nbsp;Rodrigo Almeida-Paes ,&nbsp;Susana Frases","doi":"10.1016/j.micinf.2024.105440","DOIUrl":"10.1016/j.micinf.2024.105440","url":null,"abstract":"<div><div><em>Sporothrix brasiliensis</em> is the main agent of sporotrichosis in Brazil, with few therapeutic options. This study aimed to investigate the <em>in vitro</em> efficacy of photodynamic therapy using a diode laser (InGaAIP) in combination with the photosensitizer methylene blue against <em>S. brasiliensis</em> yeasts. Additionally, we evaluated the underexplored mitochondrial activity of <em>S. brasiliensis</em> and the impact of laser treatment on the fungal mitochondrial aspects post-treatment. Three strains of <em>S. brasiliensis</em> were used, including a non-wild-type strain to itraconazole. Yeast viability was determined by counting colony-forming units. For a comprehensive analysis of irradiated versus non-irradiated cells, we assessed combined therapy with itraconazole, scanning electron microscopy of cells, and mitochondrial activity. The latter included high-resolution respirometry, membrane potential analysis, and reactive oxygen species production. Methylene blue combined with photodynamic therapy inhibited the growth of the isolates, including the non-wild-type strain to itraconazole. Photodynamic therapy induced the production of reactive oxygen species, which negatively affected mitochondrial function, resulting in decreased membrane potential and cell death. Photodynamic therapy altered the ultrastructure and mitochondrial physiology of <em>S. brasiliensis</em>, suggesting a new therapeutic approach for sporotrichosis caused by this species.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105440"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Production of a monoclonal antibody targeting the SARS-CoV-2 Omicron spike protein and analysis of SARS-CoV-2 Omicron mutations related to monoclonal antibody resistance","authors":"Jinsoo Kim ,&nbsp;Suyeon Kim ,&nbsp;Sangkyu Park ,&nbsp;Dongbum Kim ,&nbsp;Minyoung Kim ,&nbsp;Kyeongbin Baek ,&nbsp;Bo Min Kang ,&nbsp;Ha-Eun Shin ,&nbsp;Myeong-Heon Lee ,&nbsp;Younghee Lee ,&nbsp;Hyung-Joo Kwon","doi":"10.1016/j.micinf.2024.105461","DOIUrl":"10.1016/j.micinf.2024.105461","url":null,"abstract":"<div><div>SARS-CoV-2 mutations have resulted in the emergence of multiple concerning variants, with Omicron being the dominant strain presently. Therefore, we developed a monoclonal antibody (mAb) against the spike (S) protein of SARS-CoV-2 Omicron for therapeutic applications. We established the 1E3H12 mAb, recognizing the receptor binding domain (RBD) of the Omicron S protein, and found that the 1E3H12 mAb can efficiently recognize the Omicron S protein with weak affinity to the Alpha, Beta, and Mu variants, but not to the parental strain and Delta variant. Based on <em>in vitro</em> assays, the mAb demonstrated neutralizing activity against Omicron BA.1, BA.4/5, BQ.1.1, and XBB. A humanized antibody was further produced and proved to have neutralizing activity. To verify the potential limitations of the 1E3H12 mAb due to viral escape of SARS-CoV-2 Omicron variants, we analyzed the emergence of variants by whole genome deep sequencing after serial passage in cell culture. The results showed a few unique S protein mutations in the genome associated with resistance to the mAb. These findings suggest that this antibody not only contributes to the therapeutic arsenal against COVID-19 but also addresses the ongoing challenge of antibody resistance among the evolving subvariants of SARS-CoV-2 Omicron.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105461"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal immunization with poly I:C and CpG ODN adjuvants enhances the protective efficacy against Helicobacter pylori infection in mice","authors":"Min Sun,&nbsp;Yu Liu,&nbsp;Xiumei Ni,&nbsp;Runqing Tan,&nbsp;Yi Wang,&nbsp;Yajun Jiang,&nbsp;Dingxin Ke,&nbsp;Han Du,&nbsp;Gang Guo,&nbsp;Kaiyun Liu","doi":"10.1016/j.micinf.2024.105433","DOIUrl":"10.1016/j.micinf.2024.105433","url":null,"abstract":"<div><div><em>Helicobacter pylori</em> (<em>H. pylori</em>) infection is a serious public health issue, and development of vaccines is a desirable preventive strategy for <em>H. pylori</em>. Toll-like receptor (TLR) ligands have shown potential as vaccine adjuvants that induce immune responses, but polyinosinic-polycytidylic acid (poly I:C), a nucleic acid-based TLR9 ligand, is less well studied in <em>H. pylori</em> vaccine research. Here, we evaluated the effects of poly I:C and CpG oligodeoxynucleotide (CpG ODN), a nucleic acid TLR3 ligand, as adjuvants in combination with the <em>H. pylori</em> recombinant proteins LpoB and UreA to protect against <em>H. pylori</em> infection. For analysis of specific immune responses, the levels of specific antibodies and splenic cytokines were measured in the immunized mice. Compared with CpG ODN, poly I:C could induce mucosal sIgA antibody responses and reduce <em>H. pylori</em> colonization. Additionally, the combination of poly I:C and CpG ODN caused greater immunoprotection and significantly reduced gastritis, exerting synergistic effects. Analysis of splenic cytokines revealed that poly I:C mainly triggered a mixed Th1/Th2/Th17 immune response, whereas the combination of CpG ODN and poly I:C induced a Th1/Th17 immune response. Our findings indicated that increased levels of mucosal sIgA antibodies and a robust splenic Th1/Th17 immune response were associated with reduced <em>H. pylori</em> colonization in vaccinated mice. This study identified a potential TLR ligand adjuvant for developing more effective <em>H. pylori</em> vaccines.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105433"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNAs regulate the metabolic adaptation of Paracoccidioides brasiliensis during copper deprivation","authors":"Dener Lucas Araújo dos Santos ,&nbsp;Juliana Santana de Curcio ,&nbsp;Evandro Novaes ,&nbsp;Célia Maria de Almeida Soares","doi":"10.1016/j.micinf.2024.105435","DOIUrl":"10.1016/j.micinf.2024.105435","url":null,"abstract":"<div><div>Copper is an essential metal for cellular processes such as detoxification of reactive oxygen species, oxidative phosphorylation, and iron uptake. However, during infection, the host restricts the bioavailability of this micronutrient to the pathogen as a strategy to combat infection. Recently, we have shown the involvement of miRNAs as an adaptive strategy of <em>P. brasiliensis</em> upon metal deprivation such as iron and zinc. However, their role in copper limitation still needs to be elucidated. Our objective was to characterize the expression profile of miRNAs regulated during copper deprivation in <em>P. brasiliensis</em> and the putative altered processes. Through RNAseq analysis and bioinformatics, we identified 14 differentially expressed miRNAs, two of which putatively regulated oxidative stress response, beta-oxidation, glyoxylate cycle, and cell wall remodeling. Our results suggest that metabolic adaptations carried out by <em>P</em>. <em>brasiliensis</em> in copper deprivation are regulated by miRNAs.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105435"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copyright page Elsevier","authors":"","doi":"10.1016/S1286-4579(25)00057-7","DOIUrl":"10.1016/S1286-4579(25)00057-7","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105525"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}