Seto C Ogunleye, Minna Hassan, Mark L Lawrence, Hossam Abdelhamed
{"title":"The Impact of DeoRF on Listeria monocytogenes Stress Tolerance and survival.","authors":"Seto C Ogunleye, Minna Hassan, Mark L Lawrence, Hossam Abdelhamed","doi":"10.1016/j.micinf.2025.105549","DOIUrl":"https://doi.org/10.1016/j.micinf.2025.105549","url":null,"abstract":"<p><p>Listeria monocytogenes, a significant foodborne pathogen, is known for its remarkable adaptability to diverse environments through a genomic regulatory network that coordinates metabolic activities and stress responses. However, many of these genomic elements remain poorly understood. This study investigates the role of deoRF, a previously understudied member of the DeoR-family, in oxidative tolerance, intracellular infection, and virulence. Interestingly, the F2365ΔdeoRF strain showed no significant growth defects in minimal media with glucose, fructose, or sucrose, suggesting that DeoRF does not play a critical role in the uptake or metabolism of these sugars. Results showed that DeoRF plays a significant role in the ability of L. monocytogenes to adapt to oxidative stress. Additionally, DeoRF contributed significantly to cell-to-cell spread in L2 fibroblast cells, intracellular replication in macrophage cells, and virulence in mice following both intravenous and oral infection models. Transcriptomic analysis further revealed that deletion of deoRF caused downregulation of propanediol utilization, transcription regulators, phosphotransferase systems (PTS), complex networks of transcriptional regulators, and proteases genes. Conversely, sigma B regulator genes were upregulated in the ΔdeoRF strain. This study demonstrates that L. monocytogenes DeoRF contributes to pathogenicity and stress adaptation, and it is an important contributor to the complex listerial regulatory network.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105549"},"PeriodicalIF":2.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708126","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":"Porphyromonas gingivalis-Induced HuR Upregulation Suppresses SLC39A10-Derived hsa_circ_0057552 in Esophageal Squamous Cell Carcinoma.","authors":"Rui Yang, Bianli Gu, Qi Jiang, Linlin Shi, Shuoxuan Li, Yaowu Lang, Yongtian Li, Zhixiang Zuo, Shegan Gao","doi":"10.1016/j.micinf.2025.105548","DOIUrl":"https://doi.org/10.1016/j.micinf.2025.105548","url":null,"abstract":"<p><p>Porphyromonas gingivalis (P. gingivalis) is one of the main risk factors of esophageal squamous cell carcinoma (ESCC). Circular RNAs (circRNAs) have been found to play a crucial role in many types of cancer. However, its functional involvement in P. gingivalis-infected ESCC remained understudied. In this study, we investigate that overexpression of has_circ_0057552 inhibited the proliferation and motility of ESCC cells in vitro and in vivo, while silencing of has_circ_0057552 played the opposite role. Hsa_circ_0057552 was found to be downregulated in P. gingivalis-infected ESCC tissues and cells, with the extent of downregulation correlating with both the dose and duration of P. gingivalis infection. Mechanistically, P. gingivalis infection significantly reduced the stability of hsa_circ_0057552 in ESCC cells, and Human Antigen R (HuR) was identified as a key regulator mediating this destabilization. The interaction between hsa_circ_0057552 and HuR was confirmed. Furthermore, hsa_circ_0057552 suppressed SLC39A10 mRNA expression by competitively inhibiting HuR binding to SLC39A10 transcripts. This study delineates a P. gingivalis-HuR-hsa_circ_0057552 axis that may modulate SLC39A10 availability through competitive RNA-protein interactions. This mechanistic framework suggests a dual therapeutic approach: microbial-targeted eradication of P. gingivalis combined with hsa_circ_0057552 restoration therapy to disrupt oncogenic signaling cascades.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105548"},"PeriodicalIF":2.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698989","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":"Averting collapse: Reimagining the NTDs ecosystem through G20 health diplomacy and science innovation.","authors":"Maple Goh, Peter J Hotez","doi":"10.1016/j.micinf.2025.105547","DOIUrl":"10.1016/j.micinf.2025.105547","url":null,"abstract":"<p><p>The recent termination of the U.S. Government's neglected topical diseases (NTD) mass treatment program, following similar cuts by the UK, threatens decades of progress. Without a strategic reset, NTDs may re-emerge, exacerbating poverty across Africa and beyond. We call for a broadened donor base and reframing NTD control as a shared global interest, especially as NTDs rise in G20 nations due to climate change and urbanization. This moment demands investment in sustainable tools, like NextGen vaccines and biologics, and greater leadership from G20 countries. While USAID's exit is a setback, opportunities arise for decolonizing global health and fostering new partnerships.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105547"},"PeriodicalIF":2.7,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682786","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":"Therapeutic strategies to combat Staphylococcus aureus infections in cystic fibrosis.","authors":"Aygun Israyilova, Gabriele Trespidi, Viola Camilla Scoffone, Silvia Buroni","doi":"10.1016/j.micinf.2025.105546","DOIUrl":"10.1016/j.micinf.2025.105546","url":null,"abstract":"<p><p>Staphylococcus aureus infections remain a great concern in people with cystic fibrosis also after the introduction of modulator therapy. Here we describe the state of the art of traditional and novel therapeutic strategies to fight both acute and chronic infections caused by sensitive and drug resistant strains.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105546"},"PeriodicalIF":2.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649888","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}
Jurate Skerniskyte, Marina Valente Barroso, Johana Chicher, Philippe Hammann, Valerie Demais, Kathryn Wright, Serge Mostowy, Benoit S Marteyn
{"title":"Neutrophils display antibacterial defense via non-canonical LC3 decoration of extracellular bacteria.","authors":"Jurate Skerniskyte, Marina Valente Barroso, Johana Chicher, Philippe Hammann, Valerie Demais, Kathryn Wright, Serge Mostowy, Benoit S Marteyn","doi":"10.1016/j.micinf.2025.105545","DOIUrl":"10.1016/j.micinf.2025.105545","url":null,"abstract":"<p><p>Neutrophils play a pivotal role in the innate immune response to bacterial infection, being one of the first immune cells to reach infectious sites. Bacterial infection may induce neutrophil degranulation, production of neutrophil extracellular traps (NETs), or pathogen phagocytosis. While LC3 is typically linked to autophagy, here we observed a non-canonical role of LC3 when peripheral neutrophils interact with bacteria both in vivo and in vitro, using Shigella spp. as a model. Upon incubation with neutrophils, extracellular bacteria became labelled by LC3 (LC3+) along with granules-localised antimicrobial components, such as lactotransferrin, defensin, elastase, and myeloperoxidase, as demonstrated by mass spectrometry. Co-localisation of LC3 and plasma membrane-specific dyes indicated that neutrophil plasma membrane-derived elongated structures covering bacteria were responsible for the labelling. This phenomenon was associated with bacterial growth restriction and bacterial cell-death induction. Testing with specific inhibitors demonstrated that this labelling was dependent on functional V-type ATP synthase. Covering bacteria with membrane-derived elongated structures enhanced the subsequent phagocytosis of bacteria by neutrophils. Finally, the LC3 labelling rate increased with higher bacterial burden. In conclusion, we propose that this defense mechanism is beneficial when the burden of bacterial infection overwhelms neutrophils' capacity for phagocytosis.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105545"},"PeriodicalIF":2.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567633","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}
Nayara I Medeiros, Daniela Silva Oliveira, Karine S Ferreira, Tatjana S L Keesen, Luiz Paulo C Rocha, Giovane R Sousa, Marcos P S Damasio, Rafaelle C G Fares-Gusmao, Ana T Chaves, Fernanda F De Araújo, Walderez O Dutra, Rodrigo Correa-Oliveira, Manoel O C Rocha, Juliana A S Gomes
{"title":"FOXP3 gene polymorphisms are associated with indeterminate clinical form of Chagas disease.","authors":"Nayara I Medeiros, Daniela Silva Oliveira, Karine S Ferreira, Tatjana S L Keesen, Luiz Paulo C Rocha, Giovane R Sousa, Marcos P S Damasio, Rafaelle C G Fares-Gusmao, Ana T Chaves, Fernanda F De Araújo, Walderez O Dutra, Rodrigo Correa-Oliveira, Manoel O C Rocha, Juliana A S Gomes","doi":"10.1016/j.micinf.2025.105544","DOIUrl":"10.1016/j.micinf.2025.105544","url":null,"abstract":"<p><p>The forkhead box protein 3 (FOXP3) transcription factor is the main marker of regulatory T-cell (Treg) development and activation, a subpopulation involved in immune system regulation, self-tolerance, and protection against infections. We previously showed that Treg cells control the exacerbated immune response and morbidity in chronic Chagas disease, by modulating the cytokine environment and killing effector cells. Although FOXP3 gene polymorphisms have already been studied in several diseases, their role in Chagas disease is underreported. This study investigated FOXP3 gene polymorphism (rs3761548) in patients with Chronic Chagas disease and the association between FOXP3 polymorphisms (-3279 C/T and -3499 G/T) with clinical forms of the disease. We show that the -3499 G/T polymorphism of the heterozygous genotype (GT) is twice as prevalent in women with indeterminate clinical form (IND). Other analyses showed that the polymorphic allele (T + -3499 G/T) is high in women with IND, suggesting a protective role for this polymorphism. This pattern is associated with high frequency of FOXP3 in Treg cells in individuals with the IND form. Our results suggest that -3499 G/T polymorphism in the FOXP3 gene may play an important role in T. cruzi infection, contributing to control and the development of the IND clinical form.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105544"},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340192","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":"Cryptococcus neoformans and the EGFR Puzzle: Uncovering a Novel mechanism for blood-brain barrier crossing.","authors":"Jingyu Zhao, Wei Fang, Yangjie Gao, Zhenzong Fa, Guizhen Wang, Julin Gu","doi":"10.1016/j.micinf.2025.105540","DOIUrl":"10.1016/j.micinf.2025.105540","url":null,"abstract":"<p><p>This study aims to investigate the molecular mechanisms by which Cryptococcus neoformans (C. neoformans) crosses the blood-brain barrier (BBB), focusing specifically on the role of the epidermal growth factor receptor (EGFR) and its ligand, HB-EGF. Cryptococcal meningitis, caused by C. neoformans, has a high mortality rate and poses a significant threat to global public health. Research indicates that C. neoformans employs various strategies to cross the BBB, with transcellular transport being particularly critical. We observed that C. neoformans infection significantly upregulates the expression and phosphorylation of EGFR in brain microvascular endothelial cells (BMECs). Silencing EGFR using siRNA technology resulted in a marked decrease in the ability of C. neoformans to traverse the BMEC monolayer. Furthermore, C. neoformans infection also upregulates EGFR ligands, such as HB-EGF, in BMECs, thereby activating the EGFR signaling pathway. This activation involves the engagement of ADAM family metalloproteinases and the metalloprotease Mpr1 from C. neoformans. The findings of this study underscore the critical role of the host EGFR signaling pathway in the ability of C. neoformans to cross the BBB and highlight potential targets for developing new therapies for infectious meningitis.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105540"},"PeriodicalIF":2.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248714","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":"Human Endogenous RetroViruses: The iceberg view.","authors":"Patrick Küry, Patrice N Marche","doi":"10.1016/j.micinf.2025.105530","DOIUrl":"10.1016/j.micinf.2025.105530","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105530"},"PeriodicalIF":2.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248715","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}
Marta Gliźniewicz, Barbara Dołęgowska, Adrian Augustyniak, Rafał Rakoczy, Tomasz Kędzierski, Ewa Mijowska, Bartłomiej Grygorcewicz
{"title":"Effects of sequential administration of phage cocktail, ciprofloxacin, and caspofungin on Staphylococcus aureus and Candida albicans dual-species biofilms.","authors":"Marta Gliźniewicz, Barbara Dołęgowska, Adrian Augustyniak, Rafał Rakoczy, Tomasz Kędzierski, Ewa Mijowska, Bartłomiej Grygorcewicz","doi":"10.1016/j.micinf.2025.105531","DOIUrl":"10.1016/j.micinf.2025.105531","url":null,"abstract":"<p><p>Polymicrobial biofilms, including inter-kingdom ones, represent another threat in the post-antibiotic era. Therefore, many alternative solutions are being investigated, including phage-antibiotic synergy (PAS), which may be more effective due to the differing mechanisms of action of drugs and phages. In this study, we evaluated how different sequences of administering a bacteriophage cocktail, ciprofloxacin, and caspofungin affect the eradication of S. aureus and C. albicans in vitro (planktonic culture and in biofilms). In liquid culture, the phage → caspofungin → ciprofloxacin treatment completely eradicated both organisms. In biofilms, the most effective regimens were either the simultaneous application of all three agents or phages + ciprofloxacin followed by caspofungin. Therefore, the sequence of administration of drugs and phages is a key factor in achieving effective therapy and revealing the most synergistic combinations.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105531"},"PeriodicalIF":2.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199603","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}
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
{"title":"Protection conferred by mucosal novel bivalent Klebsiella pneumoniae vaccine immunization associates with presence of lung CD4+ TRM","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":"<div><div><em>Klebsiella pneumoniae</em> 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 <em>K. pneumoniae</em> 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<sup>+</sup> T<sub>RM</sub> 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 <em>K. pneumoniae</em> infection. These findings indicate that GlnH and FimA are effective candidate bivalent vaccine to fight <em>K. pneumoniae</em> infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105483"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","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}