Wouter Smit, Steven Thijsen, Robert van der Kieft, Sophie van Tol, Johan Reimerink, Chantal Reusken, Lidewij Rümke, Ailko Bossink, Gijs Limonard, Michiel Heron
{"title":"Differential vaccine-induced kinetics of humoral and cellular immune responses in SARS-CoV-2 naive and convalescent health care workers.","authors":"Wouter Smit, Steven Thijsen, Robert van der Kieft, Sophie van Tol, Johan Reimerink, Chantal Reusken, Lidewij Rümke, Ailko Bossink, Gijs Limonard, Michiel Heron","doi":"10.1093/femspd/ftac035","DOIUrl":"https://doi.org/10.1093/femspd/ftac035","url":null,"abstract":"<p><p>Effective vaccination is a key element in the exit strategy from the current severe acute respiratory syndrome-CoV coronavirus-2 (SARS-CoV-2) pandemic, and may also offer protection against severe disease from future variants of concern. Here, we prospectively monitored T-cell responses over time, using ELISpot interferon-γ (INF-y) release assays, and B-cell responses, using serological tests, after vaccination and booster with BioNTech/Pfizer mRNA (Pfizer) and Janssen vector (Janssen/Johnson & Johnson) vaccines in hospital health care workers. Vaccine recipients were divided into seropositive and seronegative individuals at baseline, in order to determine the effect of natural immunity on vaccine-induced immune kinetics. We found that convalescent individuals mounted higher spike-specific INF-y-secreting T-cell responses and B-cell-mediated IgG responses, after receiving the Janssen vaccine or the first dose of the Pfizer vaccine. IgG levels corresponded to the virus neutralization capacity as measured by VNT assay. At 8 months postvaccination, spike-specific cellular immunity waned to low levels in individuals with or without prior natural immunity, whereas waning of humoral immunity occurred predominantly in naive individuals. The booster shot effectively reinduced both cellular and humoral immune responses. To conclude, our data supports the implemented single-dose mRNA booster strategy employed in the Netherlands. Furthermore, the level of pre-existing natural immunity may be factored into determining the optimal time window between future booster vaccines.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494413/pdf/ftac035.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33458897","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}
Rupal Rai, Vinayak Singh, Bijina J Mathew, Anirudh K Singh, Shivendra K Chaurasiya
{"title":"Mycobacterial response to an acidic environment: protective mechanisms.","authors":"Rupal Rai, Vinayak Singh, Bijina J Mathew, Anirudh K Singh, Shivendra K Chaurasiya","doi":"10.1093/femspd/ftac032","DOIUrl":"https://doi.org/10.1093/femspd/ftac032","url":null,"abstract":"<p><p>Given the emergence and spread of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis (Mtb), the world faces the urgency of finding new drugs to combat tuberculosis. Understanding the biochemical/physiological processes enabling Mtb to survive the stressful environment within macrophages and acquire tolerance, resistance and persistence against the stresses are the key to developing new approaches to tackle this health problem. As Mtb gains entry into the respiratory tract and is engulfed by macrophages, lowering pH acts as a primary defence of phagosomes within macrophages and also in the centres of caseating granulomas. It becomes essential for the pathogen to maintain pH homeostasis for survival in these conditions. Acid resistance mechanisms are well known and extensively studied in other bacteria such as Escherichia coli, Lactobacillus spp., Brucella spp., Helicobacter pylori and Listeria monocytogenes. However, in the case of Mtb, acid tolerance and resistance mechanisms still need to be explored in detail. This review aims to describe the current understanding of underlying mechanisms involved in countering low pH faced by Mtb as the acid resistance/tolerance mechanisms contribute to the pathogenesis of the disease.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40711092","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":"Treponema pallidum outer membrane proteins: current status and prospects.","authors":"Jinlin Chen, Jielite Huang, Zhuoran Liu, Yafeng Xie","doi":"10.1093/femspd/ftac023","DOIUrl":"https://doi.org/10.1093/femspd/ftac023","url":null,"abstract":"<p><p>The outer membrane proteins (OMPs) of Treponema pallidum subsp. pallidum (T. pallidum), the etiological agent of the sexually transmitted disease syphilis, have long been a hot research topic. Despite many hurdles to studying the pathogen, especially the inability to manipulate T. pallidum in vitro genetically, considerable progress has been made in elucidating the structure, pathogenesis and functions of T. pallidum OMPs. In this review, we integrate this information to garner fresh insights into the role of OMPs in the diagnosis, pathogenicity and vaccine development of T. pallidum. Collectively, the essential scientific discussions herein should provide a framework for understanding the current status and prospects of T. pallidum OMPs.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40639895","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":"Burden of bacterial bloodstream infections and recent advances for diagnosis.","authors":"Susana P Costa, Carla M Carvalho","doi":"10.1093/femspd/ftac027","DOIUrl":"https://doi.org/10.1093/femspd/ftac027","url":null,"abstract":"<p><p>Bloodstream infections (BSIs) and subsequent organ dysfunction (sepsis and septic shock) are conditions that rank among the top reasons for human mortality and have a great impact on healthcare systems. Their treatment mainly relies on the administration of broad-spectrum antimicrobials since the standard blood culture-based diagnostic methods remain time-consuming for the pathogen's identification. Consequently, the routine use of these antibiotics may lead to downstream antimicrobial resistance and failure in treatment outcomes. Recently, significant advances have been made in improving several methodologies for the identification of pathogens directly in whole blood especially regarding specificity and time to detection. Nevertheless, for the widespread implementation of these novel methods in healthcare facilities, further improvements are still needed concerning the sensitivity and cost-effectiveness to allow a faster and more appropriate antimicrobial therapy. This review is focused on the problem of BSIs and sepsis addressing several aspects like their origin, challenges, and causative agents. Also, it highlights current and emerging diagnostics technologies, discussing their strengths and weaknesses.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40573204","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}
Vonetta L Edwards, Elias McComb, Jason P Gleghorn, Larry Forney, Patrik M Bavoil, Jacques Ravel
{"title":"Three-dimensional models of the cervicovaginal epithelia to study host-microbiome interactions and sexually transmitted infections.","authors":"Vonetta L Edwards, Elias McComb, Jason P Gleghorn, Larry Forney, Patrik M Bavoil, Jacques Ravel","doi":"10.1093/femspd/ftac026","DOIUrl":"https://doi.org/10.1093/femspd/ftac026","url":null,"abstract":"<p><p>2D cell culture systems have historically provided controlled, reproducible means to analyze host-pathogen interactions observed in the human reproductive tract. Although inexpensive, straightforward, and requiring a very short time commitment, these models recapitulate neither the functionality of multilayered cell types nor the associated microbiome that occurs in a human. Animal models have commonly been used to recreate the complexity of human infections. However, extensive modifications of animal models are required to recreate interactions that resemble those in the human reproductive tract. 3D cell culture models have emerged as alternative means of reproducing vital elements of human infections at a fraction of the cost of animal models and on a scale that allows for replicative experiments. Here, we describe a new 3D model that utilizes transwells with epithelial cells seeded apically and a basolateral extracellular matrix (ECM)-like layer. The model produced tissues with morphologic and physiological resemblance to human cervical and vaginal epithelia, including mucus levels produced by cervical cells. Infection by Chlamydia trachomatis and Neisseria gonorrhoeae was demonstrated, as well as the growth of bacterial species observed in the human vaginal microbiota. This enabled controlled mechanistic analyses of the interactions between host cells, the vaginal microbiota, and STI pathogens. Affordable and semi high-throughput 3D models of the cervicovaginal epithelia that are physiologically relevant by sustaining vaginal bacterial colonization, and facilitate studies of chlamydial and gonococcal infections.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"80 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9419571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10603496","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}
Bruno Blancá, Jimena Alvarez Hayes, Kristin Surmann, Valdez Hugo, Christian Hentschker, Yanina Lamberti, Uwe Völker, María Eugenia Rodriguez
{"title":"Bordetella pertussis outer membrane vesicles as virulence factor vehicles that influence bacterial interaction with macrophages.","authors":"Bruno Blancá, Jimena Alvarez Hayes, Kristin Surmann, Valdez Hugo, Christian Hentschker, Yanina Lamberti, Uwe Völker, María Eugenia Rodriguez","doi":"10.1093/femspd/ftac031","DOIUrl":"https://doi.org/10.1093/femspd/ftac031","url":null,"abstract":"<p><p>Gram-negative pathogenic bacteria constitutively shed outer membrane vesicles (OMVs) which play a significant role in the host-pathogen interaction, eventually determining the outcome of the infection. We previously found that Bordetella pertussis, the etiological agent of whooping cough, survives the innate interaction with human macrophages remaining alive inside these immune cells. Adenylate cyclase (CyaA), one of the main toxins of this pathogen, was found involved in the modulation of the macrophage defense response, eventually promoting bacterial survival within the cells. We here investigated whether B. pertussis OMVs, loaded with most of the bacterial toxins and CyaA among them, modulate the macrophage response to the bacterial infection. We observed that the pre-incubation of macrophages with OMVs led to a decreased macrophage defense response to the encounter with the bacteria, in a CyaA dependent way. Our results suggest that CyaA delivered by B. pertussis OMVs dampens macrophages protective function by decreasing phagocytosis and the bactericidal capability of these host cells. By increasing the chances of bacterial survival to the innate encounter with the macrophages, B. pertussis OMVs might play a relevant role in the course of infection, promoting bacterial persistence within the host and eventually, shaping the whole infection process.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40670322","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}
Shruti Kashyap, Harsimran Sidhu, Prince Sharma, Neena Capalash
{"title":"3-indoleacetonitrile attenuates biofilm formation and enhances sensitivity to imipenem in Acinetobacter baumannii.","authors":"Shruti Kashyap, Harsimran Sidhu, Prince Sharma, Neena Capalash","doi":"10.1093/femspd/ftac029","DOIUrl":"https://doi.org/10.1093/femspd/ftac029","url":null,"abstract":"<p><p>Acinetobacter baumannii poses a global danger due to its ability to resist most of the currently available antimicrobial agents. Furthermore, the rise of carbapenem-resistant A. baumannii isolates has limited the treatment options available. In the present study, plant auxin 3-indoleacetonitrile (3IAN) was found to inhibit biofilm formation and motility of A. baumannii at sublethal concentration. Mechanistically, 3IAN inhibited the synthesis of the quorum sensing signal 3-OH-C12-HSL by downregulating the expression of the abaI autoinducer synthase gene. 3IAN was found to reduce the minimum inhibitory concentration of A. baumannii ATCC 17978 against imipenem, ofloxacin, ciprofloxacin, tobramycin, and levofloxacin, and significantly decreased persistence against imipenem. Inhibition of efflux pumps by downregulating genes expression may be responsible for enhanced sensitivity and low persistence. 3IAN reduced the resistance to imipenem in carbapenem-resistant A. baumannii isolates by downregulating the expression of OXA β-lactamases (blaoxa-51 and blaoxa-23), outer membrane protein carO, and transporter protein adeB. These findings demonstrate the therapeutic potential of 3IAN, which could be explored as an adjuvant with antibiotics for controlling A. baumannii infections.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40615462","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}
Kaiyun Guo, Jie Duan, Jingwen Lu, Lingqiao Xiao, Liang Han, Shasha Zeng, Xin Tang, Wenjing Li, Lijun Huang, Yan Zhang
{"title":"Tumor necrosis factor-α-inducing protein of Helicobacter pylori promotes epithelial-mesenchymal transition and cancer stem-like cells properties via activation of Wnt/β-catenin signaling pathway in gastric cancer cells.","authors":"Kaiyun Guo, Jie Duan, Jingwen Lu, Lingqiao Xiao, Liang Han, Shasha Zeng, Xin Tang, Wenjing Li, Lijun Huang, Yan Zhang","doi":"10.1093/femspd/ftac025","DOIUrl":"https://doi.org/10.1093/femspd/ftac025","url":null,"abstract":"<p><p>Tumor necrosis factor-α-inducing protein (Tipα) is a newly identified toxin that promotes the inflammation and carcinogenesis caused by Helicobacter pylori. However, its mechanism of pathogenesis is still unclear. To investigate the carcinogenic mechanisms of Tipα, SGC7901 cells and SGC7901-derived cancer stem-like cells (CSCs) were stimulated by recombinant Tipα with or without Wnt/β-catenin signaling inhibitor XAV939. qRT-PCR and Western blotting were employed to detect expression of epithelial-mesenchymal transition (EMT), CSCs markers and downstream target genes of this signaling pathway. The cell migration ability was measured by wound healing assay and transwell assay. Our results indicated that Tipα promoted CSC properties of SGC7901 spheroids, including increased expression of CSC specific surface markers CD44, Oct4 and Nanog and an increased capacity for self-renewal. Tipα activated Wnt/β-catenin signaling in both SGC7901 cells or CSCs. Furthermore, Tipα induced the EMT and increased the expressions of downstream target genes of this signaling, including c-myc, cyclin D1 and CD44. However, XAV939 pretreatment inhibited Tipα-induced EMT and CSC properties in SGC7901 cells or CSCs. These results suggest that Tipα promotes EMT and CSC-like properties in gastric cancer cells through activation of Wnt/β-catenin signaling pathway, thereby accelerating the progression of gastric cancer.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40463487","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":"Examination of vertical transmission of Bartonella quintana in body lice following multiple infectious blood meals.","authors":"Lauren Kress, Rashaun Potts, Jose E Pietri","doi":"10.1093/femspd/ftac028","DOIUrl":"https://doi.org/10.1093/femspd/ftac028","url":null,"abstract":"<p><p>Bartonella quintana is a re-emerging louse-borne pathogen. Horizontal transmission from the body louse vector (Pediculus humanus humanus) to a human host occurs through contact with infectious louse feces containing a high concentration of the bacteria. However, questions have remained about whether vertical transmission from infected vectors to their progeny, which could significantly influence the dynamics of transmission to humans, occurs in body lice. To address this subject, we performed a series of controlled laboratory experiments that examined the presence of B. quintana on the surface of and within eggs produced by female body lice that were provisioned multiple infectious blood meals to recapitulate the natural pathogen acquisition process. Our results demonstrate that B. quintana DNA can be detected from the surface of eggs by qPCR due to vertical transfer of infectious feces to the egg sheath during or after oviposition. However, viable B. quintana could not be cultured from the hemolymph of adult female lice or from within eggs that were surface sterilized, indicating a lack of true transovarial transmission. Based on this evidence, vertical transfer of B. quintana from infected adult lice to their eggs probably has a limited impact on the dynamics of transmission to humans.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"80 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384838/pdf/ftac028.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119636","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":"Impact on quinolone resistance of plasmid-mediated quinolone resistance gene and mutations in quinolone resistance-determining regions in extended spectrum beta lactamase-producing Klebsiella pneumoniae isolated from urinary tract infection patients.","authors":"Reo Onishi, Katsumi Shigemura, Kayo Osawa, Young-Min Yang, Koki Maeda, Hiroshi Tanimoto, Mitsuki Kado, Shiuh-Bin Fang, Shian-Ying Sung, Takayuki Miyara, Masato Fujisawa","doi":"10.1093/femspd/ftac030","DOIUrl":"https://doi.org/10.1093/femspd/ftac030","url":null,"abstract":"<p><p>Klebsiella pneumoniae is a typical pathogen in urinary tract infections (UTI), and the emergence of extended spectrum beta-lactamase (ESBL)-producing strains has been frequently reported, accompanied by higher quinolone resistance rates. There are two major mechanisms of quinolone resistance, mutations in quinolone resistance-determining regions (QRDR) and the presence of the plasmid-mediated quinolone resistance (PMQR) genes. This study aimed to investigate quinolone resistance among 105 ESBL-producing K. pneumoniae specimens isolated from UTI patients in Indonesia. These were characterized for antimicrobial resistance to nalidixic acid, ciprofloxacin, and levofloxacin, QRDR mutations in gyrA and parC and the presence of PMQR genes. We found that 84.8% of the collected isolates were resistant to at least one of the quinolones. QRDR mutation in gyrA was observed in 49.5% of these strains and parC mutations in 61.0%. PMQR genes were identified in 84.8% of strains. The QRDR mutations clearly had a greater effect on resistance than the PMQR genes. In conclusion, we found high quinolone resistance rates in Indonesian ESBL-producing K. pneumoniae, in which QRDR mutation played a major role.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40647830","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}