首页 > 最新文献

Emerging Microbes & Infections最新文献

英文 中文
TianTan vaccinia virus-based EBV vaccines targeting both latent and lytic antigens elicits potent immunity against lethal EBV challenge in humanized mice. 基于天坛疫苗病毒的 EBV 疫苗同时针对潜伏抗原和溶解抗原,可在人源化小鼠体内激发针对致命性 EBV 挑战的强效免疫力。
IF 8.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-13 DOI: 10.1080/22221751.2024.2412640
Xinyu Zhang, Yanhong Chen, Shuhui Wang, Ling Zhong, Zheng Xiang, Xiao Zhang, Shanshan Zhang, Xiang Zhou, Wanlin Zhang, Yan Zhou, Qiuting Zhang, Jingtong Liang, Yanran Luo, Yufei Wang, Ling Chen, Xiaoping Ye, Qisheng Feng, Mu-Sheng Zeng, Ying Liu, Yi-Xin Zeng, Yiming Shao, Miao Xu

Epstein-Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.

摘要天疱疮病毒(EBV)感染与多种上皮癌和淋巴瘤有关。目前,开发预防性 EBV 疫苗的工作主要集中在诱导中和抗体上。然而,鉴于 EBV 感染在原发感染后会终身持续存在,因此理想的疫苗应该针对 EBV 生命周期的多个阶段引起体液免疫和细胞免疫反应。本研究使用 DNA 载体和天坛疫苗病毒表达 EBV 的关键抗原,包括 BZLF1、EBNA1、EBNA3B 和 gH/gL,以产生多抗原疫苗。通过激活 BZLF1、EBNA1 和 EBNA3B 特异性 T 细胞,表达所有四种抗原的多抗原疫苗和表达 BZLF1、EBNA1 和 EBNA3B 的多抗原疫苗显示出了相当的保护效果,分别 100% 和 80% 的人源化小鼠免于 EBV 诱导的致命 B 细胞淋巴瘤。与针对单一潜伏 EBNA1 或 EBNA3B 的疫苗相比,表达溶菌蛋白 BZLF1 的疫苗能激发更强的 T 细胞反应,并提供更优越的保护。在我们的人源化小鼠模型中,仅表达 gH/gL 的疫苗没有表现出 T 细胞保护作用。我们的研究表明,针对 EBV 生命周期的潜伏期和溶解期诱导强效细胞应答的 EBV 疫苗具有预防 EBV 诱导的 B 细胞淋巴瘤的潜力。
{"title":"TianTan vaccinia virus-based EBV vaccines targeting both latent and lytic antigens elicits potent immunity against lethal EBV challenge in humanized mice.","authors":"Xinyu Zhang, Yanhong Chen, Shuhui Wang, Ling Zhong, Zheng Xiang, Xiao Zhang, Shanshan Zhang, Xiang Zhou, Wanlin Zhang, Yan Zhou, Qiuting Zhang, Jingtong Liang, Yanran Luo, Yufei Wang, Ling Chen, Xiaoping Ye, Qisheng Feng, Mu-Sheng Zeng, Ying Liu, Yi-Xin Zeng, Yiming Shao, Miao Xu","doi":"10.1080/22221751.2024.2412640","DOIUrl":"10.1080/22221751.2024.2412640","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2412640"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388956","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}
引用次数: 0
Genetic characterization and receptor binding analysis of a novel H5N1 HPAI virus with a H6Nx-derived PA gene in Guangdong, China. 中国广东带有 H6Nx 衍生 PA 基因的新型 H5N1 高致病性禽流感病毒的遗传特征和受体结合分析。
IF 8.4 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1080/22221751.2024.2417857
Jieheng He, Jing Liu, Zhanfei Yan, Gaojie Chen, Runzhi Liu, Yu Yang, Yulin Yan, Sheng Yuan, Jinyue Guo, Yong Li, Hai Yu, Zhaoping Liang, Tao Ren, Shujian Huang, Feng Wen
{"title":"Genetic characterization and receptor binding analysis of a novel H5N1 HPAI virus with a H6Nx-derived PA gene in Guangdong, China.","authors":"Jieheng He, Jing Liu, Zhanfei Yan, Gaojie Chen, Runzhi Liu, Yu Yang, Yulin Yan, Sheng Yuan, Jinyue Guo, Yong Li, Hai Yu, Zhaoping Liang, Tao Ren, Shujian Huang, Feng Wen","doi":"10.1080/22221751.2024.2417857","DOIUrl":"10.1080/22221751.2024.2417857","url":null,"abstract":"","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2417857"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460743","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}
引用次数: 0
Differences in oxazolidinone resistance mechanisms and small colony variants emergence of Staphylococcus aureus induced in an in vitro resistance development model. 体外抗药性发展模型诱导的金黄色葡萄球菌对噁唑烷酮的抗药性机制和小菌落变种出现的差异。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-02-06 DOI: 10.1080/22221751.2023.2292077
Moritz Staudacher, Julian Frederic Hotz, Richard Kriz, Katharina Schefberger, Lisa Schneider, Kathrin Spettel, Peter Starzengruber, Jürgen Benjamin Hagemann, Amelie Leutzendorff, Heinz Burgmann, Heimo Lagler

Invasive Staphylococcus aureus infections are associated with a high burden of disease, case fatality rate and healthcare costs. Oxazolidinones such as linezolid and tedizolid are considered potential treatment choices for conditions involving methicillin resistance or penicillin allergies. Additionally, they are being investigated as potential inhibitors of toxins in toxin-mediated diseases. In this study, linezolid and tedizolid were evaluated in an in vitro resistance development model for induction of resistance in S. aureus. Whole genome sequencing was conducted to elucidate resistance mechanisms through the identification of causal mutations. After inducing resistance to both linezolid and tedizolid, several partially novel single nucleotide variants (SNVs) were detected in the rplC gene, which encodes the 50S ribosome protein L3 in S. aureus. These SNVs were found to decrease the binding affinity, potentially serving as the underlying cause for oxazolidinone resistance. Furthermore, in opposite to linezolid we were able to induce phenotypically small colony variants of S. aureus after induction of resistance with tedizolid for the first time in literature. In summary, even if different antibiotic concentrations were required and SNVs were detected, the principal capacity of S. aureus to develop resistance to oxazolidinones seems to differ between linezolid and tedizolid in-vivo but not in vitro. Stepwise induction of resistance seems to be a time and cost-effective tool for assessing resistance evolution. Inducted-resistant strains should be examined and documented for epidemiological reasons, if MICs start to rise or oxazolidinone-resistant S. aureus outbreaks become more frequent.

侵袭性金黄色葡萄球菌感染造成的疾病负担、病死率和医疗成本都很高。利奈唑胺和泰迪唑胺等恶唑烷酮类药物被认为是治疗甲氧西林耐药性或青霉素过敏症的潜在药物。此外,它们还被研究用作毒素介导疾病的潜在毒素抑制剂。本研究在体外耐药性发展模型中评估了利奈唑胺和泰迪唑胺对金黄色葡萄球菌耐药性的诱导作用。研究人员对这两种药物进行了全基因组测序,以通过鉴定因果突变来阐明耐药性机制。在诱导出对利奈唑胺和泰迪唑胺的耐药性后,在金黄色葡萄球菌中编码 50S 核糖体蛋白 L3 的 rplC 基因中检测到了几个部分新的单核苷酸变异(SNV)。这些 SNV 可降低结合亲和力,可能是导致奥沙唑烷酮耐药性的根本原因。此外,与利奈唑胺相反,我们首次在文献中发现了金黄色葡萄球菌对泰迪唑胺产生耐药性后诱导出的表型小菌落变异。总之,即使所需的抗生素浓度和检测到的 SNV 不同,金黄色葡萄球菌对噁唑烷酮类药物产生耐药性的主要能力似乎在体内而非体外与利奈唑胺和泰迪唑胺不同。逐步诱导耐药性似乎是评估耐药性演变的一种省时、省钱的工具。如果 MIC 开始升高或对恶唑烷酮类药物产生耐药性的金黄色葡萄球菌疫情变得更加频繁,则应从流行病学的角度对诱导产生耐药性的菌株进行检查和记录。
{"title":"Differences in oxazolidinone resistance mechanisms and small colony variants emergence of <i>Staphylococcus aureus</i> induced in an <i>in vitro</i> resistance development model.","authors":"Moritz Staudacher, Julian Frederic Hotz, Richard Kriz, Katharina Schefberger, Lisa Schneider, Kathrin Spettel, Peter Starzengruber, Jürgen Benjamin Hagemann, Amelie Leutzendorff, Heinz Burgmann, Heimo Lagler","doi":"10.1080/22221751.2023.2292077","DOIUrl":"10.1080/22221751.2023.2292077","url":null,"abstract":"<p><p>Invasive <i>Staphylococcus aureus</i> infections are associated with a high burden of disease, case fatality rate and healthcare costs. Oxazolidinones such as linezolid and tedizolid are considered potential treatment choices for conditions involving methicillin resistance or penicillin allergies. Additionally, they are being investigated as potential inhibitors of toxins in toxin-mediated diseases. In this study, linezolid and tedizolid were evaluated in an <i>in vitro</i> resistance development model for induction of resistance in <i>S. aureus</i>. Whole genome sequencing was conducted to elucidate resistance mechanisms through the identification of causal mutations. After inducing resistance to both linezolid and tedizolid, several partially novel single nucleotide variants (SNVs) were detected in the <i>rplC</i> gene, which encodes the 50S ribosome protein L3 in <i>S. aureus</i>. These SNVs were found to decrease the binding affinity, potentially serving as the underlying cause for oxazolidinone resistance. Furthermore, in opposite to linezolid we were able to induce phenotypically small colony variants of <i>S. aureus</i> after induction of resistance with tedizolid for the first time in literature. In summary, even if different antibiotic concentrations were required and SNVs were detected, the principal capacity of <i>S. aureus</i> to develop resistance to oxazolidinones seems to differ between linezolid and tedizolid <i>in-vivo</i> but not <i>in vitro</i>. Stepwise induction of resistance seems to be a time and cost-effective tool for assessing resistance evolution. Inducted-resistant strains should be examined and documented for epidemiological reasons, if MICs start to rise or oxazolidinone-resistant <i>S. aureus</i> outbreaks become more frequent.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2292077"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487004","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}
引用次数: 0
Capsid protein mediated evasion of IRAK1-dependent signalling is essential to Sindbis virus neuroinvasion and virulence in mice. 由帽盖蛋白介导的IRAK1依赖性信号转导的规避是辛比斯病毒侵入小鼠神经并产生毒性的关键。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-01-07 DOI: 10.1080/22221751.2023.2300452
V Douglas Landers, Milton Thomas, Cierra M Isom, Deepa Karki, Kevin J Sokoloski

ABSTRACTAlphaviruses are arthropod-borne, single-stranded positive-sense RNA viruses that are recognized as rapidly emerging pathogens. Despite being exquisitely sensitive to the effects of the innate immune response alphaviruses can readily replicate, disseminate, and induce pathogenesis in immunologically competent hosts. Nonetheless, how alphaviruses evade the induction of an innate immune response prior to viral gene expression, or in non-permissive infections, is unknown. Previously we reported the identification of a novel host/pathogen interaction between the viral Capsid (CP) protein and the host IRAK1 protein. The CP/IRAK1 interaction was determined to negatively impact IRAK1-dependent PAMP detection in vitro, however, the precise importance of the CP/IRAK1 interaction to alphaviral infection remained unknown. Here we detail the identification of the CP/IRAK1 interaction determinants of the Sindbis virus (SINV) CP protein and examine the importance of the interaction to alphaviral infection and pathogenesis in vivo using an interaction deficient mutant of the model neurotropic strain of SINV. Importantly, these interaction determinants are highly conserved across multiple Old-World alphaviruses, including Ross River virus (RRV), Mayaro virus (MAYV), Chikungunya virus (CHIKV), and Semliki Forest virus (SFV). In the absence of a functional CP/IRAK1 interaction, SINV replication is significantly restricted and fails to disseminate from the primary site of inoculation due to the induction of a robust type-I Interferon response. Altogether these data indicate that the evasion of IRAK1-dependent signalling is critical to overcoming the host innate immune response and the in vivo data presented here demonstrate the importance of the CP/IRAK1 interaction to neurovirulence and pathogenesis.

阿尔法病毒是一种节肢动物传播的单链正义 RNA 病毒,被认为是快速出现的病原体。尽管阿尔法病毒对先天性免疫反应非常敏感,但它仍能在具有免疫能力的宿主体内轻易复制、传播并诱发病变。然而,阿尔法病毒如何在病毒基因表达之前或在非允许性感染中逃避先天性免疫反应的诱导尚不清楚。在此之前,我们报道了病毒帽状体(CP)蛋白与宿主 IRAK1 蛋白之间的新型宿主/病原体相互作用。CP/IRAK1 相互作用被确定会对体外 IRAK1 依赖性 PAMP 检测产生负面影响,但 CP/IRAK1 相互作用对阿尔法病毒感染的确切重要性仍然未知。在这里,我们详细鉴定了辛比斯病毒(SINV)CP 蛋白中的 CP/IRAK1 相互作用决定因子,并利用 SINV 的模式神经毒株的相互作用缺陷突变体研究了这种相互作用对阿尔法病毒感染和体内发病机制的重要性。重要的是,这些相互作用决定因子在多种旧世界α病毒中高度保守,包括罗斯河病毒(RRV)、马亚罗病毒(MAYV)、基孔肯雅病毒(CHIKV)和塞姆利基森林病毒(SFV)。在缺乏功能性 CP/IRAK1 相互作用的情况下,SINV 的复制会受到明显限制,并且由于诱导了强大的 I 型干扰素反应,SINV 无法从主要接种点扩散。总之,这些数据表明,逃避 IRAK1 依赖性信号传导对于克服宿主先天性免疫反应至关重要,本文提供的体内数据证明了 CP/IRAK1 相互作用对神经病毒感染和发病的重要性。
{"title":"Capsid protein mediated evasion of IRAK1-dependent signalling is essential to Sindbis virus neuroinvasion and virulence in mice.","authors":"V Douglas Landers, Milton Thomas, Cierra M Isom, Deepa Karki, Kevin J Sokoloski","doi":"10.1080/22221751.2023.2300452","DOIUrl":"10.1080/22221751.2023.2300452","url":null,"abstract":"<p><p><b>ABSTRACT</b>Alphaviruses are arthropod-borne, single-stranded positive-sense RNA viruses that are recognized as rapidly emerging pathogens. Despite being exquisitely sensitive to the effects of the innate immune response alphaviruses can readily replicate, disseminate, and induce pathogenesis in immunologically competent hosts. Nonetheless, how alphaviruses evade the induction of an innate immune response prior to viral gene expression, or in non-permissive infections, is unknown. Previously we reported the identification of a novel host/pathogen interaction between the viral Capsid (CP) protein and the host IRAK1 protein. The CP/IRAK1 interaction was determined to negatively impact IRAK1-dependent PAMP detection <i>in vitro</i>, however, the precise importance of the CP/IRAK1 interaction to alphaviral infection remained unknown. Here we detail the identification of the CP/IRAK1 interaction determinants of the Sindbis virus (SINV) CP protein and examine the importance of the interaction to alphaviral infection and pathogenesis <i>in vivo</i> using an interaction deficient mutant of the model neurotropic strain of SINV. Importantly, these interaction determinants are highly conserved across multiple Old-World alphaviruses, including Ross River virus (RRV), Mayaro virus (MAYV), Chikungunya virus (CHIKV), and Semliki Forest virus (SFV). In the absence of a functional CP/IRAK1 interaction, SINV replication is significantly restricted and fails to disseminate from the primary site of inoculation due to the induction of a robust type-I Interferon response. Altogether these data indicate that the evasion of IRAK1-dependent signalling is critical to overcoming the host innate immune response and the <i>in vivo</i> data presented here demonstrate the importance of the CP/IRAK1 interaction to neurovirulence and pathogenesis.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2300452"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073580","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}
引用次数: 0
First report of Candida auris in Guangdong, China: clinical and microbiological characteristics of 7 episodes of candidemia. 中国广东首次报告念珠菌病:7 例念珠菌血症的临床和微生物学特征。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-01-07 DOI: 10.1080/22221751.2023.2300525
Yaqin Peng, Yue Liu, Xuegao Yu, Jingchun Fang, Zhaowang Guo, Kang Liao, Peisong Chen, Penghao Guo

Candida auris is an emerging multidrug-resistant fungal pathogen worldwide. To date, it has not been reported in Guangdong, China. For the first time, we reported 7 cases of C. auris candidemia from two hospitals in Guangdong. The clinical and microbiological characteristics of these cases were investigated carefully. Two geographic clades, i.e. III and I, were found popular in different hospitals by whole genome sequencing analyses. All C. auris isolates from bloodstream were resistant to fluconazole, 5 of which belonged to Clade III harbouring VF125AL mutation in the ERG11 gene. The isolates with Clade I presented Y132F mutation in the ERG11 gene as well as resistance to amphotericin B. All isolates exhibited strong biofilm-forming capacity and non-aggregative phenotype. The mean time from admission to onset of C. auris candidemia was 39.4 days (range: 12 - 80 days). Despite performing appropriate therapeutic regimen, 42.9% (3/7) of patients experienced occurrences of C. auris candidemia and colonization after the first positive bloodstream. C. auris colonization was still observed after the first C. auris candidemia for 81 days in some patient. Microbiologic eradication from bloodstream was achieved in 85.7% (6/7) of patients at discharge. In conclusion, this study offers a crucial insight into unravelling the multiple origins of C. auris in Guangdong, highlighting great challenges in clinical prevention and control.

白色念珠菌(Candida auris)是全球新出现的一种对多种药物产生耐药性的真菌病原体。迄今为止,中国广东尚未发现该病原体。我们首次报告了广东两家医院的 7 例念珠菌血症病例。我们仔细研究了这些病例的临床和微生物学特征。通过全基因组测序分析,发现在不同医院流行两个地理支系,即 III 和 I。所有从血液中分离出的球孢子菌都对氟康唑具有耐药性,其中 5 个属于 III 支系,ERG11 基因中含有 VF125AL 突变。所有分离株都具有很强的生物膜形成能力和非聚集表型。从入院到出现念珠菌血症的平均时间为 39.4 天(范围:12 - 80 天)。尽管采取了适当的治疗方案,42.9%(3/7)的患者在第一次血流呈阳性后又出现了念珠菌血症和定植。一些患者在第一次念珠菌阴性血症后 81 天仍观察到念珠菌定植。85.7%(6/7)的患者在出院时实现了血液中微生物的根除。总之,本研究为揭示广东地区念珠菌病的多重起源提供了重要见解,凸显了临床预防和控制方面的巨大挑战。
{"title":"First report of <i>Candida auris</i> in Guangdong, China: clinical and microbiological characteristics of 7 episodes of candidemia.","authors":"Yaqin Peng, Yue Liu, Xuegao Yu, Jingchun Fang, Zhaowang Guo, Kang Liao, Peisong Chen, Penghao Guo","doi":"10.1080/22221751.2023.2300525","DOIUrl":"10.1080/22221751.2023.2300525","url":null,"abstract":"<p><p><i>Candida auris</i> is an emerging multidrug-resistant fungal pathogen worldwide. To date, it has not been reported in Guangdong, China. For the first time, we reported 7 cases of <i>C. auris</i> candidemia from two hospitals in Guangdong. The clinical and microbiological characteristics of these cases were investigated carefully. Two geographic clades, i.e. III and I, were found popular in different hospitals by whole genome sequencing analyses. All <i>C. auris</i> isolates from bloodstream were resistant to fluconazole, 5 of which belonged to Clade III harbouring VF125AL mutation in the <i>ERG11</i> gene. The isolates with Clade I presented Y132F mutation in the <i>ERG11</i> gene as well as resistance to amphotericin B. All isolates exhibited strong biofilm-forming capacity and non-aggregative phenotype. The mean time from admission to onset of <i>C. auris</i> candidemia was 39.4 days (range: 12 - 80 days). Despite performing appropriate therapeutic regimen, 42.9% (3/7) of patients experienced occurrences of <i>C. auris</i> candidemia and colonization after the first positive bloodstream. <i>C. auris</i> colonization was still observed after the first <i>C. auris</i> candidemia for 81 days in some patient. Microbiologic eradication from bloodstream was achieved in 85.7% (6/7) of patients at discharge. In conclusion, this study offers a crucial insight into unravelling the multiple origins of <i>C. auris</i> in Guangdong, highlighting great challenges in clinical prevention and control.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2300525"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073582","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}
引用次数: 0
Immunocompetent mouse models revealed that S100A4+ monocytes/macrophages facilitate long-term Zika virus infection in the testes. 免疫功能正常的小鼠模型显示,S100A4+单核细胞/巨噬细胞有助于寨卡病毒在睾丸内的长期感染。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-01-07 DOI: 10.1080/22221751.2023.2300466
Wei Yang, Chen Zhang, Li-Bo Liu, Zhan-Zhan Bian, Jia-Tong Chang, Dong-Ying Fan, Na Gao, Pei-Gang Wang, Jing An

During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4+ monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4+ monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.

寨卡病毒(ZIKV)在全球流行期间,因其与各种严重的神经症状和对男性生育能力的潜在危害有关而引起广泛关注。然而,由于缺乏免疫功能健全的小动物模型,人们对 ZIKV 如何侵入并在男性生殖系统中存活的了解十分有限。在本研究中,通过使用抗IFNAR抗体阻断的C57BL/6雄性小鼠和人STAT2(hSTAT2)基因敲入(KI)雄性小鼠,建立了免疫功能正常的小鼠模型。感染后,即使病毒血症消失,病毒 RNA 仍可在睾丸中存活。我们还发现了ZIKV易感的S100A4+单核细胞/巨噬细胞群,它们从外周血中被招募到睾丸中,并在睾丸的ZIKV感染中发挥着关键作用。通过单细胞 RNA 测序,我们还证明了 S100A4+ 单核细胞/巨噬细胞对 ZIKV 感染睾丸的微环境有很大影响,从而促进了 ZIKV 诱导的睾丸病变。总之,本研究提出了ZIKV长期感染男性生殖系统的新机制。
{"title":"Immunocompetent mouse models revealed that S100A4<sup>+</sup> monocytes/macrophages facilitate long-term Zika virus infection in the testes.","authors":"Wei Yang, Chen Zhang, Li-Bo Liu, Zhan-Zhan Bian, Jia-Tong Chang, Dong-Ying Fan, Na Gao, Pei-Gang Wang, Jing An","doi":"10.1080/22221751.2023.2300466","DOIUrl":"10.1080/22221751.2023.2300466","url":null,"abstract":"<p><p>During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4<sup>+</sup> monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4<sup>+</sup> monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2300466"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073583","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}
引用次数: 0
The characterization of CD8+ T-cell responses in COVID-19. CD8+ t细胞在COVID-19中的应答特征
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-01-11 DOI: 10.1080/22221751.2023.2287118
Yuanting Yang, Heather Miller, Maria G Byazrova, Fabio Cndotti, Kamel Benlagha, Niels Olsen Saraiva Camara, Junming Shi, Huamei Forsman, Pamela Lee, Lu Yang, Alexander Filatov, Zhimin Zhai, Chaohong Liu

This review gives an overview of the protective role of CD8+ T cells in SARS-CoV-2 infection. The cross-reactive responses intermediated by CD8+ T cells in unexposed cohorts are described. Additionally, the relevance of resident CD8+ T cells in the upper and lower airway during infection and CD8+ T-cell responses following vaccination are discussed, including recent worrisome breakthrough infections and variants of concerns (VOCs). Lastly, we explain the correlation between CD8+ T cells and COVID-19 severity. This review aids in a deeper comprehension of the association between CD8+ T cells and SARS-CoV-2 and broadens a vision for future exploration.

本文综述了CD8+ T细胞在SARS-CoV-2感染中的保护作用。描述了未暴露队列中CD8+ T细胞介导的交叉反应反应。此外,本文还讨论了感染期间上呼吸道和下呼吸道驻留CD8+ T细胞的相关性,以及疫苗接种后CD8+ T细胞的反应,包括最近令人担忧的突破性感染和关注点变异(VOCs)。最后,我们解释了CD8+ T细胞与COVID-19严重程度之间的相关性。这一综述有助于更深入地理解CD8+ T细胞与SARS-CoV-2之间的关系,并为未来的探索拓宽了视野。
{"title":"The characterization of CD8<sup>+</sup> T-cell responses in COVID-19.","authors":"Yuanting Yang, Heather Miller, Maria G Byazrova, Fabio Cndotti, Kamel Benlagha, Niels Olsen Saraiva Camara, Junming Shi, Huamei Forsman, Pamela Lee, Lu Yang, Alexander Filatov, Zhimin Zhai, Chaohong Liu","doi":"10.1080/22221751.2023.2287118","DOIUrl":"10.1080/22221751.2023.2287118","url":null,"abstract":"<p><p>This review gives an overview of the protective role of CD8<sup>+</sup> T cells in SARS-CoV-2 infection. The cross-reactive responses intermediated by CD8<sup>+</sup> T cells in unexposed cohorts are described. Additionally, the relevance of resident CD8<sup>+</sup> T cells in the upper and lower airway during infection and CD8<sup>+</sup> T-cell responses following vaccination are discussed, including recent worrisome breakthrough infections and variants of concerns (VOCs). Lastly, we explain the correlation between CD8<sup>+</sup> T cells and COVID-19 severity. This review aids in a deeper comprehension of the association between CD8<sup>+</sup> T cells and SARS-CoV-2 and broadens a vision for future exploration.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2287118"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10786432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290668","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}
引用次数: 0
Vaccinia virus tiantan strain is inefficient in eliciting cross-reactive immunity against the emerging monkeypox virus strain. 天坛猴痘病毒株对新出现的猴痘病毒株的交叉反应免疫效果不佳
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-01-30 DOI: 10.1080/22221751.2024.2306967
Lingqian Tian, Yongli Zhang, Qiuhong Liu, Lianguo Ruan, Fuli Ren, Yang Han, Yanfang Zhang, Lei Yang, Sha Li, Hao Sun, Yecheng Zhang, Yuan Zhou, Rongjuan Pei, Fei Deng, Chaolin Huang, Xinwen Chen, Yun Wang
{"title":"Vaccinia virus tiantan strain is inefficient in eliciting cross-reactive immunity against the emerging monkeypox virus strain.","authors":"Lingqian Tian, Yongli Zhang, Qiuhong Liu, Lianguo Ruan, Fuli Ren, Yang Han, Yanfang Zhang, Lei Yang, Sha Li, Hao Sun, Yecheng Zhang, Yuan Zhou, Rongjuan Pei, Fei Deng, Chaolin Huang, Xinwen Chen, Yun Wang","doi":"10.1080/22221751.2024.2306967","DOIUrl":"10.1080/22221751.2024.2306967","url":null,"abstract":"","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2306967"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490985","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}
引用次数: 0
Genomic epidemiology and ceftazidime-avibactam high-level resistance mechanisms of Pseudomonas aeruginosa in China from 2010 to 2022. 2010-2022年中国铜绿假单胞菌基因组流行病学及头孢他啶-阿维菌素高水平耐药机制。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-03-11 DOI: 10.1080/22221751.2024.2324068
Xi Li, Longjie Zhou, Tailong Lei, Xiaofan Zhang, Jiayao Yao, Jintao He, Haiyang Liu, Heng Cai, Jingshu Ji, Yiwei Zhu, Yuexing Tu, Yunsong Yu, Hua Zhou

Ceftazidime-avibactam (CZA) resistance is a huge threat in the clinic; however, the underlying mechanism responsible for high-level CZA resistance in Pseudomonas aeruginosa (PA) isolates remains unknown. In this study, a total of 5,763 P. aeruginosa isolates were collected from 2010 to 2022 to investigate the ceftazidime-avibactam (CZA) high-level resistance mechanisms of Pseudomonas aeruginosa (PA) isolates in China. Fifty-six PER-producing isolates were identified, including 50 isolates carrying blaPER-1 in PA, and 6 isolates carrying blaPER-4. Of these, 82.1% (46/56) were classified as DTR-PA isolates, and 76.79% (43/56) were resistant to CZA. Importantly, blaPER-1 and blaPER-4 overexpression led to 16-fold and >1024-fold increases in the MICs of CZA, respectively. WGS revealed that the blaPER-1 gene was located in two different transferable IncP-2-type plasmids and chromosomes, whereas blaPER-4 was found only on chromosomes and was carried by a class 1 integron embedded in a Tn6485-like transposon. Overexpression of efflux pumps may be associated with high-level CZA resistance in blaPER-1-positive strains. Kinetic parameter analysis revealed that PER-4 exhibited a similar kcat/Km with ceftazidime and a high (∼3359-fold) IC50 value with avibactam compared to PER-1. Our study found that overexpression of PER-1 combined with enhanced efflux pump expression and the low affinity of PER-4 for avibactam contributes to high-level resistance to CZA. Additionally, the Tn6485-like transposon plays a significant role in disseminating blaPER. Urgent active surveillance is required to prevent the further spread of high-level CZA resistance in DTR-PA isolates.

头孢他啶-阿维巴坦(CZA)耐药性是临床上的一个巨大威胁;然而,铜绿假单胞菌(Pseudomonas aeruginosa,PA)分离株对头孢他啶-阿维巴坦(CZA)产生高水平耐药性的根本机制仍然未知。本研究从2010年至2022年共收集了5,763株铜绿假单胞菌分离株,调查了中国铜绿假单胞菌(PA)分离株对头孢他啶-阿维巴坦(CZA)的高水平耐药机制。研究发现了56株产生PER的分离株,包括50株携带blaPER-1的PA分离株和6株携带blaPER-4的PA分离株。其中,82.1%(46/56)被归类为 DTR-PA 分离物,76.79%(43/56)对 CZA 具有耐药性。重要的是,blaPER-1 和 blaPER-4 的过表达分别导致 CZA 的 MICs 增加了 16 倍和 >1024 倍。WGS显示,blaPER-1基因位于两个不同的可转移IncP-2型质粒和染色体上,而blaPER-4只存在于染色体上,由一个嵌入Tn6485类转座子的1类整合子携带。外排泵的过度表达可能与 blaPER-1 阳性菌株的高水平 CZA 抗性有关。动力学参数分析表明,与 PER-1 相比,PER-4 与头孢他啶的 kcat/Km 相似,与阿维菌素的 IC50 值较高(3359 倍)。我们的研究发现,PER-1的过表达加上外排泵表达的增强以及PER-4对阿维菌素的低亲和力导致了对CZA的高水平耐药性。此外,Tn6485 样转座子在传播 blaPER 方面发挥了重要作用。为防止 DTR-PA 分离物对 CZA 的高水平耐药性进一步扩散,需要进行紧急的积极监控。
{"title":"Genomic epidemiology and ceftazidime-avibactam high-level resistance mechanisms of <i>Pseudomonas aeruginosa</i> in China from 2010 to 2022.","authors":"Xi Li, Longjie Zhou, Tailong Lei, Xiaofan Zhang, Jiayao Yao, Jintao He, Haiyang Liu, Heng Cai, Jingshu Ji, Yiwei Zhu, Yuexing Tu, Yunsong Yu, Hua Zhou","doi":"10.1080/22221751.2024.2324068","DOIUrl":"10.1080/22221751.2024.2324068","url":null,"abstract":"<p><p>Ceftazidime-avibactam (CZA) resistance is a huge threat in the clinic; however, the underlying mechanism responsible for high-level CZA resistance in <i>Pseudomonas aeruginosa</i> (PA) isolates remains unknown. In this study, a total of 5,763 <i>P. aeruginosa</i> isolates were collected from 2010 to 2022 to investigate the ceftazidime-avibactam (CZA) high-level resistance mechanisms of <i>Pseudomonas aeruginosa</i> (PA) isolates in China. Fifty-six PER-producing isolates were identified, including 50 isolates carrying <i>bla</i><sub>PER-1</sub> in PA, and 6 isolates carrying <i>bla</i><sub>PER-4</sub>. Of these, 82.1% (46/56) were classified as DTR-PA isolates, and 76.79% (43/56) were resistant to CZA. Importantly, <i>bla</i><sub>PER-1</sub> and <i>bla</i><sub>PER-4</sub> overexpression led to 16-fold and >1024-fold increases in the MICs of CZA, respectively. WGS revealed that the <i>bla</i><sub>PER-1</sub> gene was located in two different transferable IncP-2-type plasmids and chromosomes, whereas <i>bla</i><sub>PER-4</sub> was found only on chromosomes and was carried by a class 1 integron embedded in a Tn<i>6485</i>-like transposon. Overexpression of efflux pumps may be associated with high-level CZA resistance in <i>bla</i><sub>PER-1</sub>-positive strains. Kinetic parameter analysis revealed that PER-4 exhibited a similar <i>kcat</i>/<i>Km</i> with ceftazidime and a high (∼3359-fold) IC50 value with avibactam compared to PER-1. Our study found that overexpression of PER-1 combined with enhanced efflux pump expression and the low affinity of PER-4 for avibactam contributes to high-level resistance to CZA. Additionally, the Tn<i>6485</i>-like transposon plays a significant role in disseminating <i>bla</i><sub>PER</sub>. Urgent active surveillance is required to prevent the further spread of high-level CZA resistance in DTR-PA isolates.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2324068"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971432","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}
引用次数: 0
Lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistant Candida auris. 兰索拉唑可干扰真菌呼吸,并与两性霉素 B 协同作用,共同对抗耐多药念珠菌。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-01 Epub Date: 2024-03-03 DOI: 10.1080/22221751.2024.2322649
Ehab A Salama, Yehia Elgammal, Aruna Wijeratne, Nadia A Lanman, Sagar M Utturkar, Atena Farhangian, Jianing Li, Brigitte Meunier, Tony R Hazbun, Mohamed N Seleem

Candida auris has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, C. auris possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we screened a panel of 727 FDA-approved drugs. We identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB's activity against C. auris. LNP also potentiates the antifungal activity of AmB against other medically important species of Candida and Cryptococcus. Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome bc1). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (∼98%) CFU reduction in the burden of C. auris in the kidneys. Our findings strongly advocate for a comprehensive evaluation of LNP as a cytochrome bc1 inhibitor for combating drug-resistant C. auris infections.

白色念珠菌已成为一种棘手的真菌病原体,发病率和死亡率都很高。两性霉素 B(AmB)是治疗侵袭性真菌念珠菌病最有效的抗真菌药物,临床分离株很少出现耐药性。然而,念珠菌对包括两性霉素 B 在内的所有现有抗真菌药物都具有极强的耐药性。为了寻求潜在的解决方案,我们筛选了 727 种美国食品及药物管理局批准的药物。我们发现质子泵抑制剂兰索拉唑(LNP)能有效增强 AmB 对阿氏杆菌的活性。LNP 还能增强 AmB 对其他重要医学念珠菌和隐球菌的抗真菌活性。我们对其作用机制的研究发现,LNP 代谢物与线粒体呼吸链(复合体 III,即细胞色素 bc1)中的一个关键靶点相互作用。这种相互作用增加了真菌细胞内的氧化应激。我们的研究结果表明,活跃的呼吸功能在 LNP 的抗真菌活性中起着关键作用。最重要的是,LNP 恢复了 AmB 在免疫功能低下小鼠模型中的疗效,使肾脏中的阴沟肠杆菌负担减少了 1.7 个菌落(∼98%)。我们的研究结果强烈建议将 LNP 作为细胞色素 bc1 抑制剂进行全面评估,以抗击耐药性蛔虫感染。
{"title":"Lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistant <i>Candida auris</i>.","authors":"Ehab A Salama, Yehia Elgammal, Aruna Wijeratne, Nadia A Lanman, Sagar M Utturkar, Atena Farhangian, Jianing Li, Brigitte Meunier, Tony R Hazbun, Mohamed N Seleem","doi":"10.1080/22221751.2024.2322649","DOIUrl":"10.1080/22221751.2024.2322649","url":null,"abstract":"<p><p><i>Candida auris</i> has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, <i>C. auris</i> possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we screened a panel of 727 FDA-approved drugs. We identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB's activity against <i>C. auris.</i> LNP also potentiates the antifungal activity of AmB against other medically important species of <i>Candida</i> and <i>Cryptococcus.</i> Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome <i>bc<sub>1</sub></i>). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (∼98%) CFU reduction in the burden of <i>C. auris</i> in the kidneys. Our findings strongly advocate for a comprehensive evaluation of LNP as a cytochrome <i>bc<sub>1</sub></i> inhibitor for combating drug-resistant <i>C. auris</i> infections.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"13 1","pages":"2322649"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10911247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021221","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}
引用次数: 0
期刊
Emerging Microbes & Infections
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1