Microbes and Infection最新文献

{"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 ,&nbsp;Noelia Carmona-Vicente ,&nbsp;Esmeralda Cano ,&nbsp;Núria Navarro ,&nbsp;Cristina Risco ,&nbsp;Joan Repullés ,&nbsp;Joaquim Segalés ,&nbsp;Júlia Vergara-Alert","doi":"10.1016/j.micinf.2025.105500","DOIUrl":"10.1016/j.micinf.2025.105500","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105500"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","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":"Immunostimulatory effects of Hsp70 fragments-modified DCs: A computational and experimental study in HIV vaccine design","authors":"Elahe Akbari ,&nbsp;Alireza Milani ,&nbsp;Parisa Moradi Pordanjani ,&nbsp;Masoud Seyedinkhorasani ,&nbsp;Elnaz Agi ,&nbsp;Azam Bolhassani","doi":"10.1016/j.micinf.2025.105480","DOIUrl":"10.1016/j.micinf.2025.105480","url":null,"abstract":"<div><h3>Background</h3><div>Dendritic cells (DCs) loaded with HIV-1 antigens have been explored as a promising therapeutic approach to overcome HIV-1 infection. Heat shock proteins (Hsps) can improve cross-presentation of linked antigens by DCs. Our aim was a comprehensive <em>in silico</em>, <em>in vitro</em>, and <em>in vivo</em> evaluation of fusion proteins comprising the <em>N</em>- and C-terminal regions of Hsp70 (<em>i.e.,</em> NT-Hsp70 and CT-Hsp70) as an adjuvant linked to HIV-1 Nef antigen in development of DCs-based vaccine candidates.</div></div><div><h3>Methods</h3><div>Computational analyses of the NT-Hsp70-Nef and CT-Hsp70-Nef fusion constructs were performed, and their structural features and docking ability with toll-like or endocytic receptors were evaluated. The effectiveness of DCs loaded with the fusion proteins in eliciting immunity was assessed in mice. Cytokine secretion levels from splenocytes exposed to single-cycle replicable (SCR) HIV-1 were also measured <em>in vitro</em>.</div></div><div><h3>Results</h3><div>The DCs pulsed with the fusion constructs induced robust cellular and humoral immune responses in mice and infected splenocytes. The CT-Hsp70 region showed better docking scores with immune receptors and superior adjuvanticity for inducing Nef-specific immune responses (Th1 and CTL activity) compared to the NT-Hsp70 region in DC-based immunization.</div></div><div><h3>Conclusions</h3><div>The CT-Hsp70-Nef protein demonstrated promising results in both computational and experimental analyses compared to the NT-Hsp70-Nef protein.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105480"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432538","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 ,&nbsp;Xuan OuYang","doi":"10.1016/j.micinf.2025.105499","DOIUrl":"10.1016/j.micinf.2025.105499","url":null,"abstract":"<div><div><em>Listeria monocytogenes</em> (<em>Lm</em>) 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 <em>Lm</em> infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105499"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","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":"Chlamydia pneumoniae relies on host glutathione for its growth and induces integrated stress response-mediated changes in macrophage glutathione metabolism","authors":"Maarit Ylätalo,&nbsp;Eveliina Taavitsainen-Wahlroos,&nbsp;Inés Reigada,&nbsp;Leena Hanski","doi":"10.1016/j.micinf.2025.105501","DOIUrl":"10.1016/j.micinf.2025.105501","url":null,"abstract":"<div><div>The obligate intracellular bacterium <em>Chlamydia pneumoniae</em> can enter into persistent phenotype, which is refractory to antibiotics and causes prolonged inflammatory state in the host. Molecular mechanisms enabling <em>C. pneumoniae</em> 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 <em>C. pneumoniae</em> growth and progeny production was studied in THP-1 macrophages and A549 epithelial cells. Results indicate that depletion of cellular GSH pools decreased <em>C. pneumoniae</em> replication, but only if the constituent amino acids were also sequestered from the culture. <em>C. pneumoniae</em> infection increased the expression of GSH biosynthetic genes but also upregulated ChaC1, an intracellular enzyme involved in GSH breakage. <em>C. pneumoniae</em> 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 <em>C. pneumoniae</em> replication. <em>C. pneumoniae</em> -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 <em>C. pneumoniae</em> requires amino acids derived from the host cell GSH pools to enable active bacterial replication.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105501"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","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":"Host–parasite interactions after in vitro infection of human macrophages by Leishmania major: Dual analysis of microRNA and mRNA profiles reveals regulation of key processes through time kinetics","authors":"Chiraz Atri ,&nbsp;Ghada Mkannez ,&nbsp;Hanène Attia ,&nbsp;Rabiaa Manel Sghaier ,&nbsp;Aymen Bali ,&nbsp;Ali Ben-Cheikh ,&nbsp;Imen Rabhi ,&nbsp;Béatrice Regnault ,&nbsp;David Piquemal ,&nbsp;Kais Ghedira ,&nbsp;Koussay Dellagi ,&nbsp;Dhafer Laouini ,&nbsp;Fatma Zahra Guerfali","doi":"10.1016/j.micinf.2025.105502","DOIUrl":"10.1016/j.micinf.2025.105502","url":null,"abstract":"<div><div>Micro-RNAs are a class of small non-coding ribonucleic acids that concomitantly regulate the expression of tens to hundreds of genes. To reduce the host's defense, <em>Leishmania</em> parasites hijack the cellular functions of their macrophage's targets through gene expression regulation. Only few studies have attempted to correlate miRNAs and mRNAs expressions within the same samples in the context of cellular parasitism.</div><div>In this study, the profiling of human macrophages, <em>in vitro</em> infected by <em>L. major</em> parasites, was performed at both the mRNA transcriptomic level and the expression of a set of 365 miRNAs, and we correlated their expressions in search for a common molecular signature.</div><div>Both mRNA and miRNA profiles were monitored during the first 24 h post-infection to capture potential time-dependent fluctuations. We then cross-correlated the cellular biological processes and the pathways associated to the predicted targets of miRNAs and to the differentially expressed mRNAs at all time points of infection on the same samples.</div><div>Besides revealing the classical activation of immune signaling pathways, the mRNA-micro-RNAs correlation study highlighted other common regulatory inflammatory biological processes, allowing identification of rapidly modulated pathways, and bringing further evidence on the early molecular cross talk that take place between <em>Leishmania</em> and infected cells.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105502"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018212","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":"No association between anti-cytomegalovirus seropositivity and arthritis: evidence from the cross-sectional epidemiology and genetic association analyses","authors":"Changzhou Feng ,&nbsp;Haining Li ,&nbsp;Ying Zhou,&nbsp;Chu Zhang,&nbsp;Jin Yang,&nbsp;Haiqing Wang","doi":"10.1016/j.micinf.2025.105529","DOIUrl":"10.1016/j.micinf.2025.105529","url":null,"abstract":"<div><div>Human cytomegalovirus (CMV), a β-herpesvirus associated with chronic inflammation and lifelong latency, has been implicated in the pathogenesis of arthritis. However, the nature of this relationship remains controversial. In this study, we integrate cross-sectional epidemiology analyses, genetic correlation assessments, and Mendelian randomization (MR) approaches to elucidate the potential association between CMV infection and arthritis-related conditions. Observational analysis of 5133 participants from the NHANES database revealed a positive association between CMV IgG seropositivity and arthritis (OR: 1.24; 95 % CI: 1.03–1.48; <em>P</em> = 0.02), particularly with the rheumatoid arthritis (RA) subtype (OR: 1.94; 95 % CI: 1.21–3.12; <em>P</em> &lt; 0.01). However, these associations lost statistical significance after adjustment for multiple covariates (all <em>P</em> &gt; 0.05). Subgroup and interaction analyses across different demographic and clinical subpopulations further confirmed the absence of these associations. Similarly, subtype analyses indicated no significant association between CMV IgG seropositivity and osteoarthritis (OA), other-arthritis, or unknown-arthritis, even before covariate adjustment. Linkage disequilibrium score regression (LDSC) analysis did not reveal a significant genetic correlation between anti-CMV IgG levels and arthritis, including RA and OA (all <em>P</em> &gt; 0.05), suggesting no shared genetic basis. Furthermore, bidirectional MR analyses found no evidence of a causal relationship between CMV antibody responses—including IgG and three CMV-related peptide antigens (pp28, pp52, and pp150)—and arthritis, RA, or OA (all <em>P</em> &gt; 0.05). Collectively, these findings suggest that previously reported positive associations between CMV seropositivity and arthritis may have been confounded by other covariates rather than reflecting a true causal relationship.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105529"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094181","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":"Chlamydia trachomatis regulates ferroptosis through the p53/SLC7A11 pathway to promote reproduction","authors":"Xinglv Wang ,&nbsp;Chengyu Tang ,&nbsp;Hongrong Wu ,&nbsp;Jingrong Zhang ,&nbsp;Lili Chen ,&nbsp;Zhongyu Li","doi":"10.1016/j.micinf.2025.105505","DOIUrl":"10.1016/j.micinf.2025.105505","url":null,"abstract":"<div><div>Genital tract <em>Chlamydia trachomatis (Ct)</em> infection is one of the most prevalent sexually transmitted infections (STIs) worldwide. However, its clinical progression is often insidious and prolonged. Understanding the mechanisms by which <em>Ct</em> influences cell death pathways is crucial for elucidating the pathogenic processes of this intracellular bacterium. Ferroptosis, a newly identified form of programmed cell death, is characterized by the iron-dependent accumulation of lipid peroxides. Despite its relevance, the interaction between <em>Ct</em> and ferroptosis remains poorly studied. In the present study, we first performed bioinformatics analysis based on RNA sequencing data under an in vitro model of <em>Ct</em> acute infection. Bioinformatics analysis revealed significant enrichment of differentially expressed genes in ferroptosis and p53 signaling pathways. Subsequently, we validated the hypothesis that <em>Ct</em> inhibits host ferroptosis by expression assays of ferroptosis-related proteins. Further cell proliferation, intracellular ferrous iron fluorescence, and lipid peroxidation assays multifaceted observations of the phenotype. Mechanistically, we found that <em>Ct</em> inhibition of ferroptosis acts by regulating the host p53/SLC7A11 pathway. Finally, indirect immunofluorescence assays demonstrated that ferroptosis decreases inclusion forming units (IFUs) of <em>Ct</em> progeny and thus affects its reproduction, which partly explains <em>Ct</em>'s survival strategy of resisting host ferroptosis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105505"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034612","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":"Comparative pathoadaptation of Mycobacterium canettii and Mycobacterium tuberculosis: Insights from assays on phagosome acidification, cytosolic access, and transcriptomics","authors":"Camila do Nascimento Araujo,&nbsp;Felipe Silva,&nbsp;Cristina Kraemer Zimpel ,&nbsp;Taiana Tainá Silva-Pereira,&nbsp;Naila Cristina Soler-Camargo,&nbsp;Filipe Menegatti de Melo ,&nbsp;Marcelo Valdemir de Araújo ,&nbsp;Ana Marcia de Sá Guimarães","doi":"10.1016/j.micinf.2025.105503","DOIUrl":"10.1016/j.micinf.2025.105503","url":null,"abstract":"<div><div>Genetic and molecular differences between <em>Mycobacterium tuberculosis</em> (Mtb) and its ancestral counterpart, <em>Mycobacterium canettii</em> (Mcan), remain poorly known. Our study aimed to compare their modulation of phagosome acidification and cytosolic access in macrophages, and their <em>in vitro</em> transcriptomes. Using spectrofluorometry, we tracked pH changes in mycobacteria-containing vacuoles in THP-1 macrophages. A single-cell FRET protocol evaluated cytosolic access of mycobacteria in these cells. Similar to Mtb, Mcan inhibits phagosome acidification and accesses the cytosol. Transcriptomic and genetic analyses reveal mutations in two-component systems (PhoPR, SenX3-RegX3, and DevRS/DosRS) and in specific genes (e.g., lactate dehydrogenase and <em>espACD</em>) driving variations in gene expression between pathogens. Moreover, Mcan upregulates genes of iron and molybdopterin metabolism compared to Mtb, suggesting a role for metals in the evolution of tuberculous mycobacteria. The upregulation of the termination factor Rho in Mtb also suggests differences in antisense transcription and/or gene expression regulation. In conclusion, phagosome modulation and cytosolic access in macrophages are ancestral traits predating the emergence of the MTBC and not exclusive to Mtb's strict pathogenic lifestyle. Additionally, gene expression regulation likely shaped the phenotypic differences between Mcan and Mtb, contributing to the evolutionary transition from an environmental Mcan-like ancestor to the MTBC's host-adapted lifestyle.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105503"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025884","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":"Pseudomonas aeruginosa-derived DnaJ induces TLR2 expression through TLR10-mediated activation of the PI3K-SGK1 pathway in macrophages","authors":"Jaehoo Lee ,&nbsp;Yongxin Jin ,&nbsp;Weihui Wu ,&nbsp;Yeji Lee ,&nbsp;Un-Hwan Ha","doi":"10.1016/j.micinf.2025.105481","DOIUrl":"10.1016/j.micinf.2025.105481","url":null,"abstract":"<div><div>TLR2 is a key component of the innate immune system, responsible for recognizing Gram-positive bacterial components and initiating inflammatory signaling cascades that activate defense responses. However, little is known about the regulatory effects of <em>Pseudomonas aeruginosa</em> (<em>P. aeruginosa</em>) on TLR2 expression. In this study, we investigated the potential link between <em>P. aeruginosa</em>-derived DnaJ and TLR2 expression in macrophages, as well as the activation of downstream signaling pathways. Our findings revealed that DnaJ significantly induced TLR2 expression in a dose- and time-dependent manner, predominantly affecting TLR2 with minimal impact on other TLRs, such as TLR4 and TLR5, which detect bacterial PAMPs. The DnaJ-mediated TLR2 induction was driven by activation of the PI3K-SGK1 signaling pathway, with TLR10 playing a crucial role in facilitating these effects. This increase in TLR2 expression led to enhanced production of inflammatory cytokines in response to secondary <em>Staphylococcus aureus</em> infections, indicating a role in boosting host defense mechanisms. In conclusion, these findings suggest that <em>P. aeruginosa</em>-derived DnaJ promotes TLR2 expression via TLR10-mediated activation of the PI3K-SGK1 pathway, thereby enhancing host immune responses against Gram-positive bacterial infections.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105481"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468450","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}