Infectious microbes & diseases最新文献

{"title":"Focus on Dysregulated Adaptive Immunity in Chronic Hepatitis B: A Promising Direction for Immunotherapy","authors":"Jiaming Zhou, Chunhong Huang, Haihong Zhu, Zhi Chen","doi":"10.1097/IM9.0000000000000082","DOIUrl":"https://doi.org/10.1097/IM9.0000000000000082","url":null,"abstract":"Abstract Hepatitis B virus (HBV) infection is a public health problem that endangers global health and is the leading cause for the occurrence and death due to hepatocellular carcinoma. Although nucleotide analogs are excellent in controlling virus replication, they have little effect on the production, stability, and transcription of covalently closed circular DNA (cccDNA) in infected hepatocytes. Moreover, only a small fraction of patients with chronic hepatitis B are cured by interferon therapy. During HBV infection, HBV-specific B cells and T cells are produced. HBV-specific T cells exert antiviral effects through cell lysis and non-cytolytic effector functions, reducing viral intermediates and cccDNA. In addition, HBV-specific B cells produce antibodies that eliminate HBV-infected liver cells through antibody-dependent cell-mediated cytotoxicity of natural killer cells. They can also bind to the hepatitis B surface antigen on the surface of the virus particle, inducing antibody-dependent phagocytosis by Kupffer cells. These responses could be combined with immunotherapy based on antiviral therapy, which may achieve a complete cure for hepatitis B. However, patients with chronic hepatitis B have immune dysfunctions, which challenges immunotherapy implementation. This review focuses on advances in adaptive immunotherapy for chronic viral hepatitis B.","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"4 1","pages":"7 - 12"},"PeriodicalIF":0.0,"publicationDate":"2022-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45450039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Efficacy of Inhaled Nitric Oxide in Preventing the Progression of Moderate to Severe COVID-19 and Its Correlation to Viral Clearance: Results of a Pilot Study","authors":"M. Moni, T. Madathil, D. Sathyapalan, Veena Menon, G. Gutjahr, F. Edathadathil, Deepthi Sureshkumar, P. Prasanna, S. Jose, Roshni Jerome, Ajai Krishnan, Indulekha C. L. Pillai, G. Kumar, Bipin Nair, V. Nizet, A. Jayant","doi":"10.1097/IM9.0000000000000079","DOIUrl":"https://doi.org/10.1097/IM9.0000000000000079","url":null,"abstract":"Abstract Hypoxic patients with coronavirus disease 2019 (COVID-19) are at high risk of adverse outcomes. Inhaled nitric oxide (iNO) has shown anti-viral and immunomodulatory effects in vitro. However, in vivo evidence of efficacy in hypoxic COVID-19 is sparse. This open label feasibility study was conducted at a single referral center in South India and evaluated the effectiveness of repurposed iNO in improving clinical outcomes in COVID-19 and its correlation with viral clearance. We recruited hypoxemic COVID-19 patients and allocated them into treatment (iNO) and control groups (1:1). Viral clearance on day 5 favored the treatment group (100% vs 72%, P < 0.01). The speed of viral clearance as adjudged by normalized longitudinal cycle threshold (Ct) values was positively impacted in the treatment group. The proportion of patients who attained clinical improvement, defined as a ≥2-point change on the World Health Organization ordinal scale, was higher in the iNO cohort (n = 11, 79%) as compared to the control group (n = 4, 36%) (odds ratio 6.42, 95% confidence interval 1.09-37.73, P = 0.032). The proportion of patients progressing to mechanical ventilation in the control group (4/11) was significantly higher than in the treatment group (0/14). The all-cause 28-day mortality was significantly different among the study arms, with 36% (4/11) of the patients dying in the control group while none died in the treatment group. The numbers needed to treat to prevent an additional poor outcome of death was estimated to be 2.8. Our study demonstrates the putative role of repurposed iNO in hypoxemic COVID-19 patients and calls for extended validation.","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"4 1","pages":"26 - 33"},"PeriodicalIF":0.0,"publicationDate":"2021-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43501719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of Plasmid-Mediated Tigecycline Resistance Gene tet(X4) in a Salmonella enterica Serovar Llandoff Isolate","authors":"Yanan Wang, Fei Liu, Xuebin Xu, Hua Huang, Na Lyu, Sufang Ma, Luping Chen, Mengyu Mao, Yongfei Hu, Xiaofeng Song, Jing Li, Yuanlong Pan, Aiping Wang, Gaiping Zhang, B. Zhu, G. Gao","doi":"10.1097/IM9.0000000000000077","DOIUrl":"https://doi.org/10.1097/IM9.0000000000000077","url":null,"abstract":"Supplemental Digital Content is available in the text Abstract The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide. We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes generated by both our laboratory and public bacterial genomes downloaded from the NCBI GenBank. The tet(X4)-positive strains were subjected to susceptibility testing and conjugation assays. The genetic features of the tet(X4)-bearing plasmid sequence were analyzed. Here, we report the identification of the plasmid-mediated tigecycline resistance gene tet(X4) in a conjugative plasmid of the Salmonella enterica serovar Llandoff strain SH16G3606, isolated from a man in China in 2016, the first reported serovar Llandoff in China as a novel sequence type ST8300. The tet(X4)-mediated resistance phenotype was successfully transferred from the Salmonella Llandoff strain into Escherichia coli J53, resulting in a 32-fold increase in the minimal inhibitory concentration of tigecycline. The tet(X4) gene was located between two copies of ISCR2 in the plasmid pSal21GXH-tetX4. To our knowledge, this is the first report of the plasmid-mediated tigecycline resistance gene tet(X4) in a Salmonella Llandoff strain isolated from a human stool sample in China. In addition, our findings demonstrated that a total of 171 isolates are carrying tet(X)-like genes distributed in 21 countries or areas across 6 continents, posing a serious threat to humans and public health. Overall, our timely discovery of the recent emergence of the tet(X4) gene in Salmonella isolates and other Enterobacteriaceae bacteria species supports the need for rapid surveillance to prevent the tet(X)-like gene from spreading.","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"3 1","pages":"198 - 204"},"PeriodicalIF":0.0,"publicationDate":"2021-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43429914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Severity of HBV-Associated Acute-on-Chronic Liver Failure Due to Irregular Medication of Nucleos(t)ide Analogs","authors":"Ying Zheng, Shu Chen, Yanxin Huang, Lisheng Jiang, Yongguo Li, Y. Lan, Shuchen Li, Yuqin Xu, Xiaodong Li, Hongwei Zhao, Yanbo Wang, Yingyun Shen, Chao Wei, Honglin Zhou, Rongshan Fan, Xiqiu Zeng, M. Jiang, Shupeng Song, Mingyan Xu","doi":"10.1097/IM9.0000000000000076","DOIUrl":"https://doi.org/10.1097/IM9.0000000000000076","url":null,"abstract":"Abstract Hepatitis B virus (HBV) represents the commonest etiologic agent of acute-on-chronic liver failure (ACLF) in most Asian countries. Nucleos(t)ide analogs (NAs) are effective in the treatment of chronic HBV infections, but may also exacerbate the disease and stimulate its development into HBV-associated ACLF if not used appropriately. The current study aimed to assess the prevalence and severity of HBV-associated ACLF as a result from irregular medication of NAs (IMNA). A total of 1134 individuals with HBV-associated ACLF in nine hospitals in Heilongjiang Province were enrolled in this study between 2005 and 2015. Among these, 777 chronic hepatitis B (CHB) and 357 HBV-associated liver cirrhosis cases were classified based on various predisposing factors, including IMNA, HBV reactivation (HBVR), infections, treatment drugs, alcohol use and others (hepatitis C virus, hepatitis E virus, gastrointestinal bleeding and unknown reasons). The percentage and improvement rate were examined. Among individuals with HBV-associated ACLF and CHB, IMNA was found in 9.01%, HBVR in 46.20%, infections in 9.52%, treatment drugs in 14.67%, alcohol in 11.71%, and others in 24.58% as predisposing factors. Improvement rates in cases with IMNA, HBVR, infections, treatment drugs, alcohol and others were 41.43%, 58.50%, 58.11%, 56.14%, 53.85%, and 65.97%, respectively. Multivariable analysis showed that IMNA, others, infections, hepatic encephalopathy and hepatorenal syndrome were associated with prognosis. Only IMNA independently predicted HBV-associated ACLF prognosis. Overall, our study demonstrated that the percentage of IMNA-induced HBV-associated ACLF was 12.61%, and worse disease conditions resulted from IMNA compared with other factors. Thus, the suitability of treatment with NAs should be thoroughly evaluated.","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"3 1","pages":"205 - 209"},"PeriodicalIF":0.0,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49342938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent SARS-CoV-2 Outlook and Implications in a COVID-19 Vaccination Era.","authors":"Teddy Ehianeta, Said Abdulrahman Salim Mzee, Muslimat Kehinde Adebisi, Oluwayemisi Ehianeta","doi":"10.1097/IM9.0000000000000072","DOIUrl":"10.1097/IM9.0000000000000072","url":null,"abstract":"<p><p>While repurposed drugs came in handy earlier in the wake of the coronavirus disease 2019 (COVID-19) pandemic, vaccination has been considered a more sustainable approach. The recent spikes have been linked to \"double,\" \"triple,\" and even multi-mutant variants, thus renewing calls for deeper structural and functional insights of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a lead to rationale design of therapeutics, vaccines, and point-of-care diagnostics. There is a repertoire of findings from the earliest SARS-CoV-2 molecular mimicry to evade host immunity cum host immune responses to the role of the viral glycocalyx in modulating the susceptibility and severity of infection through attraction and repulsive interactions. Recently, molecular studies of some viral components that aid infection in the face of vaccination seem unending. In addition, the wave of infections and the attendant case fatality ratios have necessitated the need for emergency use authorizations for COVID-19 vaccines and in vitro diagnostics. This review provides key updates of SARS-CoV-2, current antigenic and formulation strategies, with emergency use authorizations considerations for future vaccine candidates and diagnostics. We also premise that despite the difficulty in modeling and analyzing glycans, understanding and exploiting their roles in the SARS-CoV-2 architecture is fundamental to glycan-based COVID-19 vaccines devoid of inconsistent clinical outcomes.</p>","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"3 1","pages":"125-133"},"PeriodicalIF":0.0,"publicationDate":"2021-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49329212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass Spectrometry Analysis of SARS-CoV-2 Nucleocapsid Protein Reveals Camouflaging Glycans and Unique Post-Translational Modifications.","authors":"Zeyu Sun, Xiaoqin Zheng, Feiyang Ji, Menghao Zhou, Xiaoling Su, Keyi Ren, Lanjuan Li","doi":"10.1097/IM9.0000000000000071","DOIUrl":"10.1097/IM9.0000000000000071","url":null,"abstract":"<p><p>The devastating coronavirus disease 2019 (COVID-19) pandemic has prompted worldwide efforts to study structural biological traits of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its viral components. Compared to the Spike protein, which is the primary target for currently available vaccines or antibodies, knowledge about other virion structural components is incomplete. Using high-resolution mass spectrometry, we report a comprehensive post-translational modification (PTM) analysis of nucleocapsid phosphoprotein (NCP), the most abundant structural component of the SARS-CoV-2 virion. In addition to phosphoryl groups, we show that the SARS-CoV-2 NCP is decorated with a variety of PTMs, including <i>N</i>-glycans and ubiquitin. Based on newly identified PTMs, refined protein structural models of SARS-CoV-2 NCP were proposed and potential immune recognition epitopes of NCP were aligned with PTMs. These data can facilitate the design of novel vaccines or therapeutics targeting NCP, as valuable alternatives to the current vaccination and treatment paradigm that is under threat of the ever-mutating SARS-CoV-2 Spike protein.</p>","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"3 1","pages":"149-157"},"PeriodicalIF":0.0,"publicationDate":"2021-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43723048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of FOXP3+ Regulatory T Cells on Infectious and Inflammatory Diseases","authors":"Yakun Bai, Fang Gao, Dan Li, Suyuan Ji, Shuijun Zhang, Wenzhi Guo, Bin Li","doi":"10.1097/IM9.0000000000000070","DOIUrl":"https://doi.org/10.1097/IM9.0000000000000070","url":null,"abstract":"Abstract CD4+CD25+FOXP3+ regulatory T cells (Tregs) contribute to the maintenance of immune homeostasis and tolerance in the body. The expression levels and functional stability of FOXP3 control the function and plasticity of Tregs. Tregs critically impact infectious diseases, especially by regulating the threshold of immune responses to pathogenic microorganisms. The functional regulatory mechanism and cell-specific surface markers of Tregs in different tissues and inflammatory microenvironments have been investigated in depth, which can provide novel ideas and strategies for immunotherapies targeting infectious diseases.","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"3 1","pages":"187 - 197"},"PeriodicalIF":0.0,"publicationDate":"2021-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47062095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Site-Specific Conjugation of Cell Wall Polyrhamnose to Protein SpyAD Envisioning a Safe Universal Group A Streptococcal Vaccine.","authors":"Nina J Gao, Satoshi Uchiyama, Lucy Pill, Samira Dahesh, Joshua Olson, Leslie Bautista, Shilpa Maroju, Aym Berges, Janet Z Liu, Raymond H Zurich, Nina van Sorge, Jeff Fairman, Neeraj Kapoor, Victor Nizet","doi":"10.1097/im9.0000000000000044","DOIUrl":"10.1097/im9.0000000000000044","url":null,"abstract":"<p><p>Development of an effective vaccine against the leading human bacterial pathogen group A Streptococcus (GAS) is a public health priority. The species defining group A cell wall carbohydrate (GAC, Lancefield antigen) can be engineered to remove its immunodominant N-acetylglucosamine (GlcNAc) side chain, implicated in provoking autoimmune cross-reactivity in rheumatic heart disease, leaving its polyrhamnose core (GAC^PR). Here we generate a novel protein conjugate of the GAC^PR and test the utility of this conjugate antigen in active immunization. Instead of conjugation to a standard carrier protein, we selected SpyAD, a highly conserved GAS surface protein containing both B-cell and T-cell epitopes relevant to the bacterium that itself shows promise as a vaccine antigen. SpyAD was synthesized using the XpressTM cell-free protein expression system, incorporating a non-natural amino acid to which GAC^PR was conjugated by site-specific click chemistry to yield high molecular mass SpyAD-GAC^PR conjugates and avoid disruption of important T-cell and B-cell immunological epitopes. The conjugated SpyAD-GAC^PR elicited antibodies that bound the surface of multiple GAS strains of diverse M types and promoted opsonophagocytic killing by human neutrophils. Active immunization of mice with a multivalent vaccine consisting of SpyAD-GAC^PR, together with candidate vaccine antigens streptolysin O and C5a peptidase, protected against GAS challenge in a systemic infection model and localized skin infection model, without evidence of cross reactivity to human heart or brain tissue epitopes. This general approach may allow GAC to be safely and effectively included in future GAS subunit vaccine formulations with the goal of broad protection without autoreactivity.</p>","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"3 1","pages":"87-100"},"PeriodicalIF":2.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11501091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49323705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial Infections in Cirrhosis","authors":"M. Tonon, P. Angeli, S. Piano","doi":"10.1097/IM9.0000000000000065","DOIUrl":"https://doi.org/10.1097/IM9.0000000000000065","url":null,"abstract":"Abstract Bacterial infections are the most common trigger of acute decompensation of cirrhosis. The occurrence of infections in cirrhosis is associated with the development of organ dysfunctions, failures, and acute on chronic liver failure. The combination of infections and organ dysfunction/acute on chronic liver failure dramatically increases the mortality risk in these patients. Infections in cirrhosis are a big challenge for clinicians, since the mortality from sepsis is increasing in these patients worldwide. The rapid and progressive spread of multiresistant bacteria has been blamed for the increased mortality rate. Several studies have shown that early diagnosis and appropriate administration of antibiotic treatment are crucial for improving prognosis in these patients. Moreover, the prevention and treatment of acute kidney injury and organ failures are fundamental parts of management of infections in cirrhosis. Herein we provided a concise and updated review of the literature on bacterial infections in patients with cirrhosis.","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"3 1","pages":"117 - 124"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48917821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Hyperbaric Oxygen an Effective Treatment for the Prevention of Complications in SARS-CoV-2 Asymptomatic Patients?","authors":"P. Longobardi, Klarida Hoxha, Fabiana Perreca","doi":"10.1097/IM9.0000000000000064","DOIUrl":"https://doi.org/10.1097/IM9.0000000000000064","url":null,"abstract":"Abstract Is hyperbaric oxygen therapy (HBO2T) useful to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in positive asymptomatic patients? Asymptomatic persons seem to account for approximately 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. In patients dying from SARS-CoV-2 infection, the mean number of concomitant diseases was 3.6 (median 3, standard deviation 2.1). Many of these diseases are correlated with the nitric oxide synthase genetic polymorphism and reduced nitric oxide synthesis [risk for coronary heart disease: odds ratio (95% confidence interval) = 2.74 (1.78–3.85)]. HBO2T significantly increases the production of nitric oxide and free radicals which, in laboratory tests, inhibit the replication of the SARS-CoV. HBO2T upregulates hypoxia inducible factor, which promotes the expression of human antiviral peptides: defensins and cathelicidins, both effective to block the virus. Thus, HBO2T regulates the inflammatory response. We share our pilot study conclusions as a basis for clinical trials.","PeriodicalId":73374,"journal":{"name":"Infectious microbes & diseases","volume":"3 1","pages":"109 - 111"},"PeriodicalIF":0.0,"publicationDate":"2021-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48010177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}