Emerging Microbes & Infections最新文献

{"title":"Genomic characterization of invasive <i>Neisseria meningitidis</i> in Spain (2011/12-2022/23): expansion of clonal complex 213 and the potential threat to 4CMenB vaccine strain coverage.","authors":"Josep Roca-Grande, Alba Mir-Cros, Carmen Muñoz-Almagro, Mayli Lung, Alba Bellés-Bellés, Jordi Càmara, Emilia Cercenado, M Ángeles Galán-Ladero, Andrea Martín-Nalda, Albert Moreno-Mingorance, Daniel Navarro de la Cruz, M Ángeles Orellana, Begoña Palop, Amaresh Pérez-Argüello, Guillem Puigsech-Boixeda, M Dolores Quesada, Alba Rivera, Ana Rodriguez-Fernandez, Enrique Ruiz de Gopegui, Carolina Sarvisé, Aleix Soler-Garcia, Belén Viñado, Nieves Larrosa, Juan José González-López","doi":"10.1080/22221751.2025.2482696","DOIUrl":"10.1080/22221751.2025.2482696","url":null,"abstract":"<p><p>Invasive meningococcal disease (IMD) is associated with significant global morbidity and mortality and is addressed by conjugated polysaccharide and subcapsular vaccines. In Spain, data on 4CMenB vaccine strain coverage and antimicrobial susceptibility are limited. This study aimed to describe the genomic epidemiology, predict 4CMenB vaccine strain coverage, and assess antimicrobial susceptibility of 323 <i>Neisseria meningitidis</i> isolates causing IMD, collected from 57 Clinical Microbiology Laboratories in Spain over 12 years (2011/12-2022/23). Whole genome sequencing was performed to identify serogroup, clonal complex (cc), and antimicrobial resistance determinants. Vaccine strain coverage for serogroup B (MenB) isolates was predicted using the genetic Meningococcal Antigen Typing System approach. The most prevalent serogroups were B (57.9%), W (21.4%), C (10.4%), and Y (8.4%). MenB predominated throughout most seasons, except during the 2019/20 season when serogroup W peaked. Post-COVID-19 pandemic, MenB remained the most frequent (70.2%). Thirteen cc were identified among MenB isolates, with cc213 being the most prevalent (40.1%). Only 28.9% of MenB isolates were predicted to be covered by 4CMenB, with cc213 showing an exceptionally low coverage rate (5.3%) due to antigenic variants poorly targeted by the vaccine. Notably, cc213 was responsible for twice the proportion of MenB cases in 4CMenB-vaccinated versus unvaccinated. All isolates were susceptible to third generation cephalosporins, and 13.5% showed penicillin resistance. This study highlights the alarming prevalence of cc213 among MenB IMD cases in Spain and the limited 4CMenB coverage against this cc. The disproportionate representation of cc213 in vaccinated individuals underscores its potential to compromise vaccine effectiveness.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2482696"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum levels of neurofilament light chain and glial fibrillary acidic protein correlate with disease severity in patients with West Nile virus infection.","authors":"Alessandro Dinoto, Monia Pacenti, Sara Mariotto, Davide Abate, Vittoria Lisi, Sorsha Satto, Stefania Vogiatzis, Vanessa Chiodega, Sara Carta, Sergio Ferrari, Luisa Barzon","doi":"10.1080/22221751.2024.2447606","DOIUrl":"10.1080/22221751.2024.2447606","url":null,"abstract":"<p><p>West Nile virus (WNV) is a neurotropic mosquito-borne orthoflavivirus, representing a relevant public health threat. Identification of biomarkers that would predict the course of WNV infection is of interest for the early identification of patients at risk and for supporting decisions on therapeutic interventions. In this study, serum levels of glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL), which are markers of brain tissue damage and inflammation, were analysed in 103 subjects with laboratory-confirmed WNV infection, comprising 13 asymptomatic blood donors, 23 with WN fever (WNF), 50 with encephalitis/meningoencephalitis (E/ME) and 17 with acute flaccid paralysis (AFP). In addition, 55 WNV-negative subjects with fever, encephalitis or healthy asymptomatic were included as controls. Age-adjusted levels of both sNfL and sGFAP were significantly higher in patients with neuroinvasive disease than in those with fever or asymptomatic (both WNV-positive and WNV-negative), suggesting a broad association of these biomarkers with systemic inflammation and brain injury resulting from infection. In WNV patients, the combined analysis of sNfL and sGFAP early after symptom onset allowed discrimination between neuroinvasive disease and fever with 67.2% sensitivity and 91.3% specificity, but not between E/ME and AFP. Furthermore, high levels of sNfL and sGFAP were significantly associated with prolonged hospital stay, intensive care unit admission and the occurrence of death or severe sequelae. Detection of WNV RNA in CSF was associated with increased sGFAP. In conclusion, our study indicates the potential utility of sNfL and sGFAP as biomarkers of WNV disease severity and adverse outcome.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2447606"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sharp rise in high-virulence Bordetella pertussis with macrolides resistance in Northern China.","authors":"Yahong Hu, Lin Zhou, Qianqian Du, Wei Shi, Qinghong Meng, Lin Yuan, Huili Hu, Lijuan Ma, Dongfang Li, Kaihu Yao","doi":"10.1080/22221751.2025.2475841","DOIUrl":"10.1080/22221751.2025.2475841","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the evolution of antigen genotype and antimicrobial resistance distribution of <i>Bordetella pertussis</i> (<i>B. pertussis</i>) from 2019 to 2023 in northern China.</p><p><strong>Methods: </strong>Polymerase chain reaction (PCR) amplification and sequencing were utilized to identify the seven antigen genotypes (<i>ptxA, ptxC, ptxP, prn, fim2, fim3, tcfA</i>). E-test and Kirby-Bauer (K-B) disc diffusion were employed to determine the minimum inhibitory concentration (MIC) and zone of inhibition for <i>B. pertussis</i> against antimicrobial agents. Subsequently, 50 isolates were chosen for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing.</p><p><strong>Results: </strong>A total of 442 <i>B. pertussis</i> isolates were determined. The strains with high virulence harbouring <i>ptxP3</i> allele surged from 13.5% (21/155) in 2019-2021 to 93.0% (267/287) in 2022-2023. Concurrently, the erythromycin resistance <i>B. pertussis</i> (ERBP) in <i>ptxP3</i> isolates markedly rose from 42.9% (9/21) in 2019-2021 to 100% (267/267) in 2022-2023. The majority of <i>ptxP3</i> isolates (76.0%,219/288) exhibited the <i>ptxA1/ptxC1/prn2/fim2-1/fim3A/tcfA-2</i> genotype. Among the 442 confirmed patients, the children aged 3-14 years escalated rapidly from 13.5% in 2019 to 45.6% in 2023. The MT28 strains were responsible for 66.0% (33/50) of the tested ones, in which ERBP was prevalent at 87.9% (29/33). All the present sequenced <i>ptxP3</i>-ERBP strains (31/31) were clustered into the sub-lineage IVd.</p><p><strong>Conclusions: </strong>These results suggested the clonal spread of the <i>ptxP3</i>-ERBP lineage of <i>B. pertussis</i> with high virulence and macrolides resistance could be an important cause of the recent pertussis resurgence in China. Furthermore, the increased cases among pre-school and school-aged children underscore the importance of booster vaccination in this population.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2475841"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol inhibits African swine fever virus replication <i>via</i> the Nrf2-mediated reduced glutathione and antioxidative activities.","authors":"Di Liu, Lian-Feng Li, Huanjie Zhai, Tao Wang, Jing Lan, Mengxiang Cao, Meng Yao, Yijing Wang, Jia Li, Xin Song, Yuan Sun, Hua-Ji Qiu","doi":"10.1080/22221751.2025.2469662","DOIUrl":"10.1080/22221751.2025.2469662","url":null,"abstract":"<p><p>African swine fever (ASF) is a highly contagious and severe infectious disease caused by African swine fever virus (ASFV). The disease significantly threatens the sustainable development of the global pig industry. Unfortunately, to date, no safe and efficacious vaccines are commercially available except in Vietnam. Antioxidative stress is a critical factor in antiviral strategies. In this study, we show that ASFV infection elevates the level of reactive oxygen species (ROS) and suppresses the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway <i>in vitro</i> and <i>in vivo</i>. Moreover, overexpressing Nrf2 can significantly inhibit ASFV replication. Through high-throughput screening of natural small molecules against ASFV, we identify resveratrol (RES), an Nrf2 activator, as a compound capable of inducing the cellular antiviral responses and effectively inhibiting ASFV replication in primary porcine alveolar macrophages (PAMs). Notably, untargeted metabolomics profiling reveals that glutathione emerges as a primary differential metabolite related to the antiviral activities of RES against ASFV. Mechanistically, RES exerts its antiviral effects and attenuates the elevated level of ROS caused by ASFV infection by inducing the production of reduced glutathione (GSH) <i>via</i> the activation of the Nrf2 signaling pathway. In conclusion, RES exhibits broad efficacy as a potentially effective compound for inhibiting ASFV infection and alleviating the oxidative stress induced by ASFV infection <i>via</i> the Nrf2 signaling pathway.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2469662"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of a novel reassortant highly pathogenic avian influenza clade 2.3.4.4b A(H5N2) Virus, 2024.","authors":"Rabeh El-Shesheny, Mokhtar Gomaa, Mohamed El Sayes, Mina Nabil Kamel, Ahmed El Taweel, Omnia Kutkat, Mohamed GabAllah, Amany Elkhrsawy, Hager Emam, Yassmin Moatasim, Ahmed Kandeil, Pamela P McKenzie, Richard J Webby, Mohamed Ahmed Ali, Ghazi Kayali","doi":"10.1080/22221751.2025.2455601","DOIUrl":"10.1080/22221751.2025.2455601","url":null,"abstract":"<p><p>Reassortant highly pathogenic avian influenza A(H5N2) clade 2.3.4.4.b viruses were detected from ducks and environmental samples in Egypt, June 2024. Genomic and phylogenetic analyses revealed a novel genotype produced by the reassortment of an A(H5N1) clade 2.3.3.4b virus with an A(H9N2) G1-like virus. Monitoring the spread of this virus is important.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2455601"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuraminidase reassortment and oseltamivir resistance in clade 2.3.4.4b A(H5N1) viruses circulating among Canadian poultry, 2024.","authors":"Anthony V Signore, Tomy Joseph, Charlene Ranadheera, Cassidy N G Erdelyan, Tamiru N Alkie, Sugandha Raj, Lemarie Pama, Ifeoluwa Ayilara, Tamiko Hisanaga, Oliver Lung, Nathalie Bastien, Yohannes Berhane","doi":"10.1080/22221751.2025.2469643","DOIUrl":"10.1080/22221751.2025.2469643","url":null,"abstract":"<p><p>We report the detection of a clade 2.3.4.4b A(H5N1) reassortant virus with a neuraminidase surface protein derived from a North American lineage low-pathogenic avian influenza virus. This virus caused a widespread and ongoing outbreak across 45 poultry farms in British Columbia, Canada. Isolates from 8 farms reveal a mutation in the neuraminidase protein (H275Y) that is exceptionally rare among clade 2.3.4.4b viruses (present in 0.045% of publicly available clade 2.3.4.4b isolates). NA-H275Y is a well-known marker of resistance to the neuraminidase inhibitor oseltamivir. We demonstrate that this substitution maintains its resistance phenotype on the genetic background of H5N1 clade 2.3.4.4b viruses.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2469643"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence of Mpox clade IIb infection in primary human alveolar epithelium.","authors":"Thanaphon Namporn, Suwimon Manopwisedjaroen, Montien Ngodngamthaweesuk, Ekawat Pasomsub, Natnicha Jiravejchakul, Rattatammanoon Saengfak, Marea Jikka Nealiga, Arunsajee Sea-Be, Aalok Basu, Parichart Naruphontjirakul, Suradej Hongeng, Teresa D Tetley, Arunee Thitithanyanont, Pakatip Ruenraroengsak","doi":"10.1080/22221751.2025.2477845","DOIUrl":"10.1080/22221751.2025.2477845","url":null,"abstract":"<p><p>Monkeypox virus (Mpox) has been recognized for causing distinct skin lesions and is primarily transmitted through skin and sexual contact. To date, the transmissibility and pathogenesis of the Mpox virus in distal human lung has never been completely explored. Here the transmission pathways and Mpox tropism on patient-derived air-liquid epithelium (ALE) model fabricated using isolated primary human alveolar epithelial cells (hAECs) were investigated. hAECs were cultured and exposed to the Mpox virus clade IIb isolated from the patient. DNA, proteins, and the tropism were elucidated using polymerase chain reaction (PCR), Western blot, and high-content fluorescent imaging. Transmission electron microscopy (TEM) was employed to systematically observe the cellular distribution of viral particles. Viral titres were determined by TCID₅₀ assay. Innate immune response and inflammatory mediators were measured using Milliplex® multiplex and ELISA analysis. Pathology at alveolar barrier integrity was determined using transepithelial electrical resistance (TEER) analysis. The study included mock-infected cells as control. Mpox virus significantly infected 42.82% of total hAEC populations. The prominent observed pathology included a significant reduction in TEER values, loss of tight junction protein, presence of tunnelling nanotubes (TNTs), and syncytium morphology. Four stages of Mpox biogenesis were clearly observed without significant activation of IL-6, MIP1alpha, TNF-α, and Galectin-9, although IL-1β were subtly promoted. The developed patient-derived ALE is a versatile model for Mpox virus clade IIb infection reflecting respiratory transmission competence of the Mpox. Postinfection lung pathogenesis demonstrated alveolar barrier damage without significant inflammation, raising concerns about possible immune evasion by the virus.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2477845"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An mpox quadrivalent mRNA vaccine elicits sustained and protective immunity in mice against lethal vaccinia virus challenge.","authors":"Entao Li, Qiyuan Yang, Wenyu Xie, Qizan Gong, Xiaoping Guo, Jinge Zhou, Jiachen Zhang, Xia Chuai, Yucai Wang, Sandra Chiu","doi":"10.1080/22221751.2024.2447619","DOIUrl":"10.1080/22221751.2024.2447619","url":null,"abstract":"<p><p>Assessing the long-term efficacy of MPXV vaccine candidates is crucial for the global response to the ongoing mpox epidemic. Built upon our previous study of the mpox quadrivalent mRNA vaccine, herein we reported that MPXV-1103 could elicit sustained humoral and cellular immunity in mice, including the induction of MPXV A35/B6/A29/M1-specific IgG antibodies, VACV neutralizing antibodies and activated cytotoxic CD8⁺T cells, which provides 100% protection against lethal VACV challenge even at 280 days after the first vaccination. Our results provide critical insights for orthopoxvirus vaccine development.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2447619"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic islands and molecular mechanisms relating to drug-resistance in <i>Clostridioides</i> (<i>Clostridium</i>) <i>difficile</i> PCR ribotype 176.","authors":"Krutova Marcela, Kovarovic Vojtech, Brajerova Marie, Demay Fanny, Zikova Jaroslava, Prasad Suhanya, Soltesova Anna, Novakova Elena, Pituch Hanna, Kuijper Ed, Smits Wiep Klaas, Balikova Novotna Gabriela","doi":"10.1080/22221751.2025.2482698","DOIUrl":"10.1080/22221751.2025.2482698","url":null,"abstract":"<p><strong>Objectives: </strong>To analyse characteristics of <i>Clostridioides difficile</i> PCR ribotype 176 clinical isolates from Poland, the Czech Republic and Slovakia with regard to the differences in its epidemiology.</p><p><strong>Methods: </strong>Antimicrobial susceptibility testing and whole genome sequencing were performed on a selected group of 22 clonally related isolates as determined by multilocus variable-number tandem repeat analysis (n = 509). Heterologous expression and functional analysis of the newly identified methyltransferase were performed.</p><p><strong>Results: </strong>Core genome multilocus sequence typing found 10-37 allele differences. All isolates were resistant to fluoroquinolones (<i>gyr</i>A_p. T82I), aminoglycosides with <i>aac</i>(6')-<i>Ie-aph</i>(2'')-<i>Ia</i> in six isolates. Erythromycin resistance was detected in 21/22 isolates and 15 were also resistant to clindamycin with <i>erm</i>B gene. Fourteen isolates were resistant to rifampicin with <i>rpo</i>B_p. R505K or p. R505K/H502N, and five to imipenem with <i>pbp</i>1_p. P491L and <i>pbp</i>3_p. N537K. P<i>nim</i>B^G together with <i>nim</i>B_p. L155I were detected in all isolates but only five were resistant to metronidazole on chocolate agar. The <i>cfr</i>E, <i>van</i>Z1 and <i>cat</i>-like genes were not associated with linezolid, teicoplanin and chloramphenicol resistance, respectively. The genome comparison identified six transposons carrying antimicrobial resistance genes. The <i>erm</i>B gene was carried by new Tn<i>7808</i>, Tn<i>6189</i> and Tn<i>6218</i>-like. The <i>aac</i>(6')-<i>Ie-aph</i>(2'')-<i>Ia</i> were carried by Tn<i>6218</i>-like and new Tn<i>7806</i> together with <i>cfr</i>E gene. New Tn<i>7807</i> carried a <i>cat</i>-like gene. Tn<i>6110</i> and new Tn<i>7806</i> contained an RlmN-type 23S rRNA methyltransferase, designated MrmA, associated with high-level macrolide resistance in isolates without <i>erm</i>B gene.</p><p><strong>Conclusions: </strong>Multidrug-resistant <i>C. difficile</i> PCR ribotype 176 isolates carry already described and unique transposons. A novel mechanism for erythromycin resistance in <i>C. difficile</i> was identified.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2482698"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High glucose heightens vulnerability to <i>Leishmania braziliensis</i> infection in human macrophages by hampering the production of reactive oxygen species through TLR2 and TLR4.","authors":"Ícaro Bonyek-Silva, Rana Bastos, Sara Nunes, Rafael Tibúrcio, Alexsandro Lago, Juliana Silva, Lucas P Carvalho, Ricardo Khouri, Sergio M Arruda, Aldina Barral, Viviane Boaventura, Henrique C Serezani, Edgar M Carvalho, Cláudia Ida Brodskyn, Natalia Machado Tavares","doi":"10.1080/22221751.2025.2475824","DOIUrl":"10.1080/22221751.2025.2475824","url":null,"abstract":"<p><p>Diabetes increases susceptibility to infections, including <i>Leishmania braziliensis</i> (<i>Lb</i>). Our group previously demonstrated that diabetic patients with cutaneous leishmaniasis (CL) take longer to heal lesions compared to non-diabetics. Since macrophages play a critical role in CL pathogenesis, we investigated how high glucose levels impact their response during <i>Lb</i> infection. Macrophages cultured in high glucose conditions showed increased parasite load than those in normal glucose conditions. The production of inflammatory mediators was similar between glucose conditions, but basal reactive oxygen species (ROS) production was elevated under high glucose conditions and remained unchanged after <i>Lb</i> infection, indicating glucose-induced oxidative stress does not control the parasite. In contrast, macrophages in normal glucose conditions, exhibited increased ROS production only after infection<i>.</i> Additionally, high glucose reduced TLR2 and TLR4 expression, which was also observed after <i>Lb</i> infection. TLR2/4 inhibition increased <i>Lb</i> infection in normal glucose conditions, mediated by TLR-dependent ROS production. However, this mechanism was absent under high glucose conditions, where elevated basal ROS production appeared TLR-independent. Biopsies from diabetic CL patients corroborated these findings, showing decreased TLR2 and TLR4 expression compared to non-diabetics. These findings suggest that high glucose levels induce oxidative stress and reduces TLR expression, impairing macrophage functions and rendering them less effective at controlling Lb infection.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2475824"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}