{"title":"Characterization of novel HIV fusion-inhibitory lipopeptides with the M-T hook structure","authors":"Xiuzhu Geng , Xiaohui Ding , Yuanmei Zhu , Huihui Chong , Yuxian He","doi":"10.1016/j.micinf.2024.105366","DOIUrl":"10.1016/j.micinf.2024.105366","url":null,"abstract":"<div><div><span><span>Combination antiretroviral therapy (cART) has significantly improved the survival of HIV-infected individuals, but long-term treatment can cause side-effects and drug resistance; thus, the development of new antivirals is of importance. We previously identified an M-T hook structure and accordingly designed short-peptide fusion inhibitor<span><span> 2P23, which mainly targets the gp41<span> pocket site and displays potent, broad-spectrum anti-HIV activity. In this study, we continuingly characterized the amino acid sequences of peptide and lipopeptide-based inhibitors containing the M-T hook residues. Among a group of lipopeptides, </span></span>stearic acid (C18)-modified LP-25 and LP-29 exhibited greatly improved inhibitions against divergent HIV-1 subtypes and drug-resistant mutants. LP-25 and LP-29 were evaluated in </span></span>rhesus macaques, and the </span><em>ex vivo</em> inhibition data demonstrated their potent, long-lasting <em>in vivo</em><span> anti-HIV activity, with LP-25 much better than LP-29. Both the lipopeptides displayed high α-helicity, thermostability<span> and binding ability to a target-mimic peptide, and they were metabolically stable when treated with high temperature, proteolytic enzymes<span><span>, human or monkey sera and human liver microsomes. Therefore, our studies have provided critical information for understanding the structure-activity relationship of HIV fusion inhibitors with the M-T hook structure and offered novel candidates for </span>drug development.</span></span></span></div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105366"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081621","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}
Xiaolong Yao , Yuqing He , Canhe Zhu , Shangmin Yang , Jing Wu , Fei Ma , Ping Jin
{"title":"miR-190 restores the innate immune homeostasis of Drosophila by directly inhibiting Tab2 in Imd pathway","authors":"Xiaolong Yao , Yuqing He , Canhe Zhu , Shangmin Yang , Jing Wu , Fei Ma , Ping Jin","doi":"10.1016/j.micinf.2024.105399","DOIUrl":"10.1016/j.micinf.2024.105399","url":null,"abstract":"<div><div>The <em>Drosophila</em> Imd pathways are well-known mechanisms involved in innate immunity responsible for Gram-negative (G-) bacterial infection. The intensity and durability of immunity need to be finely regulated to keep sufficient immune activation meanwhile avoid excessive immune response. In this study, we firstly demonstrated that miR-190 can downregulate the expression levels of antimicrobial peptides (AMPs) in the Imd immune pathway after <em>Escherichia coli</em> infection using the miR-190 overexpression flies and the miR-190KO/+ flies. Secondly, miR-190 overexpression significantly reduces while miR-190 KO increases <em>Drosophila</em> survival rates upon lethal <em>Enterobacter cloacae</em> infection. Thirdly, we further demonstrated that miR-190 negatively regulates innate immune responses by directly targeting both RA/RB and RC isoforms of <em>Tab2.</em> In addition, the dynamic expression pattern of AMPs (<em>Dpt</em>, <em>AttA</em>, <em>CecA1</em>), <em>miR-190</em> and <em>Tab2</em> in the wild-type flies reveals that miR-190 play an important role in <em>Drosophila</em> immune homeostasis restoration at the late stage of <em>E. coli</em> infection. Collectively, our study reveals that miR-190 can downregulate the expression of AMPs by targeting <em>Tab2</em> and promote immune homeostasis restoration in <em>Drosophila</em> Imd pathway. Our study provides new insights into the regulatory mechanism of animal innate immune homeostasis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105399"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860204","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}
Zoja Germuskova , Elisa Sosa , Amaya Campillay Lagos , Hege Vangstein Aamot , Mathew A. Beale , Claire Bertelli , Jonas Björkmann , Natacha Couto , Lena Feige , Gilbert Greub , Erika Tång Hallbäck , Emma B. Hodcroft , Dag Harmsen , Laurent Jacob , Keith A. Jolley , Andre Kahles , Alison E. Mather , Richard A. Neher , Aitana Neves , Stefan Niemann , Adrian Egli
{"title":"Conference report: the first bacterial genome sequencing pan-European network conference","authors":"Zoja Germuskova , Elisa Sosa , Amaya Campillay Lagos , Hege Vangstein Aamot , Mathew A. Beale , Claire Bertelli , Jonas Björkmann , Natacha Couto , Lena Feige , Gilbert Greub , Erika Tång Hallbäck , Emma B. Hodcroft , Dag Harmsen , Laurent Jacob , Keith A. Jolley , Andre Kahles , Alison E. Mather , Richard A. Neher , Aitana Neves , Stefan Niemann , Adrian Egli","doi":"10.1016/j.micinf.2024.105410","DOIUrl":"10.1016/j.micinf.2024.105410","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105410"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanzi Zhou , Lihua Guo , Tingting Xiao , Yunbo Chen , Tao Lv , Yuan Wang , Shuntian Zhang , Hongliu Cai , Xiaohui Chi , Xiaoyang Kong , Kai Zhou , Ping Shen , Yonghong Xiao
{"title":"Characterization and dynamics of intestinal microbiota in patients with Clostridioides difficile colonization and infection","authors":"Yanzi Zhou , Lihua Guo , Tingting Xiao , Yunbo Chen , Tao Lv , Yuan Wang , Shuntian Zhang , Hongliu Cai , Xiaohui Chi , Xiaoyang Kong , Kai Zhou , Ping Shen , Yonghong Xiao","doi":"10.1016/j.micinf.2024.105373","DOIUrl":"10.1016/j.micinf.2024.105373","url":null,"abstract":"<div><div>Gut microbiota dysbiosis increases the susceptibility to <em>Clostridioides difficile</em> infection (CDI). In this study, we monitored <em>C. difficile</em> colonization (CDC) patients from no CDC status (CDN) to CDC status (CDCp) and CDI patients from asymptomatic status before CDI (PRECDI), CDI status (ONCDI), to asymptomatic status after CDI (POSTCDI). Based on metagenomic sequencing, we aimed to investigate the interaction pattern between gut microbiota and <em>C. difficile</em>. There was no significant difference of microbiota diversity between CDN and CDCp. In CDCp, Bacteroidetes and short-chain fatty acid (SCFA)-producing bacteria increased, with a positive correlation between SCFA-producing bacteria and <em>C. difficile</em> colonization. Compared with PRECDI, ONCDI and POSTCDI showed a significant decrease in microbiota diversity, particularly in Bacteroidetes and SCFA-producing bacteria, with a positive correlation between opportunistic pathogen and <em>C. difficile</em>. Fatty acid metabolism, and amino acid biosynthesis were enriched in CDN, CDCp, and PRECDI, while bile secretion was enriched in ONCDI and POSTCDI. Microbiota and metabolic pathways interaction networks in CDN and CDCp were more complex, particularly pathways in fatty acid and bile acid metabolism. Increasing of Bacteroidetes and SCFA-producing bacteria, affecting amino acid and fatty acid metabolism, is associated with colonization resistance to <em>C. difficile</em> and inhibiting the development of CDI.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105373"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of microRNAs in immune regulation and pathogenesis of Chlamydia trachomatis and Chlamydia muridarum infections: a rapid review","authors":"Chloe Meewes, Kanupriya Gupta, William M. Geisler","doi":"10.1016/j.micinf.2024.105397","DOIUrl":"10.1016/j.micinf.2024.105397","url":null,"abstract":"<div><div>MicroRNAs in <em>Chlamydia trachomatis</em> (CT) and <em>Chlamydia muridarum</em> (CM) infections are an emerging topic of research that provide knowledge that could advance vaccine development and strategies for managing infection. This rapid review summarizes human and murine studies on miRNA expression in CT and CM infections in vivo and ex vivo.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105397"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723898","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}
Ling Zhang , Miaotian Cai , Xin Zhang , Sitong Wang , Lijun Pang , Xue Chen , Caopei Zheng , Yuqing Sun , Ying Liang , Shan Guo , Feili Wei , Yulin Zhang
{"title":"Integrated analysis of microbiome and host transcriptome unveils correlations between lung microbiota and host immunity in bronchoalveolar lavage fluid of pneumocystis pneumonia patients","authors":"Ling Zhang , Miaotian Cai , Xin Zhang , Sitong Wang , Lijun Pang , Xue Chen , Caopei Zheng , Yuqing Sun , Ying Liang , Shan Guo , Feili Wei , Yulin Zhang","doi":"10.1016/j.micinf.2024.105374","DOIUrl":"10.1016/j.micinf.2024.105374","url":null,"abstract":"<div><h3>Objective</h3><div><span><span>The lung microbiota of patients with </span>pulmonary diseases<span> is disrupted and impacts the immunity. The microbiological and immune landscape of the lungs in patients with </span></span>pneumocystis pneumonia (PCP) remains poorly understood.</div></div><div><h3>Methods</h3><div><span>Multi-omics analysis and machine learning were performed on bronchoalveolar lavage fluid<span> to explore interaction between the lung microbiota and host immunity in PCP. Then we constructed a diagnostic model using differential genes with LASSO regression and validated by </span></span>qPCR<span>. The immune infiltration analysis was performed to explore the landscape of lung immunity in patients with PCP.</span></div></div><div><h3>Results</h3><div><span>Patients with PCP showed a low alpha diversity of lung microbiota, accompanied by the elevated abundance of </span><span><span>Firmicutes</span></span><span><span>, and the differential expressed genes (DEGs) analysis displayed a downregulation of </span>MAPK signaling<span><span>. The MAPK10, TGFB1, and </span>EFNA3 indicated a potential to predict PCP (AUC = 0.86). The lung immune landscape in PCP showed the lower levels of naïve CD4</span></span><sup>+</sup><span> T cells<span> and activated dendritic cells. The correlation analysis of the MAPK signaling pathway-related DEGs and the differential microorganisms at the level of phylum showed that the </span></span><span><span>Firmicutes</span></span> was negatively correlated with these DEGs.</div></div><div><h3>Conclusion</h3><div>We profiled the characteristics of lung microbiota and immune landscape in PCP, which may contribute to elucidating the mechanism of PCP.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105374"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288308","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":"Macrophage-depleted young mice are beneficial in vivo models to assess the translocation of Klebsiella pneumonia from the gastrointestinal tract to the liver in the elderly","authors":"Hitoshi Tsugawa , Shogo Tsubaki , Rika Tanaka , Sho Nashimoto , Jin Imai , Juntaro Matsuzaki , Katsuto Hozumi","doi":"10.1016/j.micinf.2024.105371","DOIUrl":"10.1016/j.micinf.2024.105371","url":null,"abstract":"<div><div>Pathobionts are commensal intestinal microbiota capable of causing systemic infections under specific conditions, such as environmental changes or aging. However, it is unclear how pathobionts are recognized by the intestinal mucosal immune system under physiological conditions. This study demonstrates that the gut pathobiont <em>Klebsiella pneumoniae</em> causes injury to the epithelium and translocates to the liver in specific pathogen-free mice treated with clodronate-liposomes that depleted macrophages. In the clodronate-liposome-treated mice, indigenous classical <em>K. pneumoniae</em> (cKp) with non-K1/K2 capsular serotypes were isolated from the liver, indicating that gut commensal cKp translocated from the gastrointestinal tract to the liver due to the depletion of intestinal macrophages. Oral inoculation of isolated cKp to clodronate-liposome-treated mice significantly reduced the survival rates compared to that of non-treated mice. Our findings demonstrate that intestinal mucosal macrophages play a pivotal role in sensing commensal cKp and suppressing their translocation to the liver. This study demonstrates that clodronate-liposome-treated mouse models are effective for screening and evaluating drugs that prevent the translocation of cKp to the liver, providing new insights into the development of preventive protocols against <em>K. pneumoniae</em> infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105371"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heng Heng , Ling Yang , Zhiwei Zheng , Chen Yang , Xuemei Yang , Wenxing Zhao , Ruanyang Sun , Kaichao Chen , Lianwei Ye , Jun Li , Edward Wai-Chi Chan , Sheng Chen
{"title":"Characterization of Acinetobacter baumannii at a tertiary hospital in Guangzhou: a genomic and clinical study","authors":"Heng Heng , Ling Yang , Zhiwei Zheng , Chen Yang , Xuemei Yang , Wenxing Zhao , Ruanyang Sun , Kaichao Chen , Lianwei Ye , Jun Li , Edward Wai-Chi Chan , Sheng Chen","doi":"10.1016/j.micinf.2024.105380","DOIUrl":"10.1016/j.micinf.2024.105380","url":null,"abstract":"<div><div><span><em>Acinetobacter baumannii</em></span><span><span> (AB) infections have become a global public health<span> concern due to the continued increase in the incidence of infection and the rate of resistance to carbapenems. This study aimed to investigate the genomic features of </span></span>AB<span> strains recovered from a tertiary hospital and assess the clinical implications of the findings. A total of 217 AB strains were collected between 2016 and 2018 at a tertiary hospital in Guangzhou, with 183 (84.33%) being carbapenem-resistant AB (CRAB), with the main mechanism being the carriage of the </span></span><em>bla</em><sub>OXA-23</sub><span> gene. The overall mortality rate<span><span> of patients caused by such strains was 15.21% (n = 33). Artificial lung ventilation and the use of </span>meropenem<span><span> were mortality risk factors in AB-infected patients, while KL2 AB infection was negatively associated. Core genome multilocus sequence typing and clustering analysis were performed on the integrated AB genome collection from the NCBI database and this study to illustrate the population structure among China. The results revealed diverse core genome profiles (n = 17) among AB strains from China, and strains from this single hospital exhibited most of the core genome profiles (n = 13), suggesting genetic variability within the hospital and transmission across the country. These findings show that the high transmission potential of the CRAB strains and </span>meropenem<span> usage that confers a selective advantage of CRAB clinically are two major factors that pose significant challenges to the effective clinical management of AB infections. Understanding the genetic features and transmission patterns of clinical AB strains is crucial for the effective control of infections caused by this pathogen.</span></span></span></span></div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105380"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443059","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":"Biomolecular condensates with liquid properties formed during viral infections","authors":"Damien Glon, Benjamin Léonardon, Ariane Guillemot, Aurélie Albertini, Cécile Lagaudrière-Gesbert, Yves Gaudin","doi":"10.1016/j.micinf.2024.105402","DOIUrl":"10.1016/j.micinf.2024.105402","url":null,"abstract":"<div><div>During a viral infection, several membraneless compartments with liquid properties are formed. They can be of viral origin concentrating viral proteins and nucleic acids, and harboring essential stages of the viral cycle, or of cellular origin containing components involved in innate immunity. This is a paradigm shift in our understanding of viral replication and the interaction between viruses and innate cellular immunity.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 8","pages":"Article 105402"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}