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  1. Article ; Online: Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis

    Anna Allué-Guardia / Rajagopalan Saranathan / John Chan / Jordi B. Torrelles

    International Journal of Molecular Sciences, Vol 22, Iss 2, p

    2021  Volume 735

    Abstract: The current emergence of multi-, extensively-, extremely-, and total-drug resistant strains of Mycobacterium tuberculosis poses a major health, social, and economic threat, and stresses the need to develop new therapeutic strategies. The notion of phage ... ...

    Abstract The current emergence of multi-, extensively-, extremely-, and total-drug resistant strains of Mycobacterium tuberculosis poses a major health, social, and economic threat, and stresses the need to develop new therapeutic strategies. The notion of phage therapy against bacteria has been around for more than a century and, although its implementation was abandoned after the introduction of drugs, it is now making a comeback and gaining renewed interest in Western medicine as an alternative to treat drug-resistant pathogens. Mycobacteriophages are genetically diverse viruses that specifically infect mycobacterial hosts, including members of the M. tuberculosis complex. This review describes general features of mycobacteriophages and their mechanisms of killing M. tuberculosis , as well as their advantages and limitations as therapeutic and prophylactic agents against drug-resistant M. tuberculosis strains. This review also discusses the role of human lung micro-environments in shaping the availability of mycobacteriophage receptors on the M. tuberculosis cell envelope surface, the risk of potential development of bacterial resistance to mycobacteriophages, and the interactions with the mammalian host immune system. Finally, it summarizes the knowledge gaps and defines key questions to be addressed regarding the clinical application of phage therapy for the treatment of drug-resistant tuberculosis.
    Keywords Mycobacterium tuberculosis ; drug-resistance ; mycobacteriophages ; phage therapy ; lung mucosa ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 572
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Host- and Age-Dependent Transcriptional Changes in Mycobacterium tuberculosis Cell Envelope Biosynthesis Genes after Exposure to Human Alveolar Lining Fluid

    Anna Allué-Guardia / Andreu Garcia-Vilanova / Angélica M. Olmo-Fontánez / Jay Peters / Diego J. Maselli / Yufeng Wang / Joanne Turner / Larry S. Schlesinger / Jordi B. Torrelles

    International Journal of Molecular Sciences, Vol 23, Iss 983, p

    2022  Volume 983

    Abstract: Tuberculosis (TB) infection, caused by the airborne pathogen Mycobacterium tuberculosis ( M.tb ), resulted in almost 1.4 million deaths in 2019, and the number of deaths is predicted to increase by 20% over the next 5 years due to the COVID-19 pandemic. ... ...

    Abstract Tuberculosis (TB) infection, caused by the airborne pathogen Mycobacterium tuberculosis ( M.tb ), resulted in almost 1.4 million deaths in 2019, and the number of deaths is predicted to increase by 20% over the next 5 years due to the COVID-19 pandemic. Upon reaching the alveolar space, M.tb comes into close contact with the lung mucosa before and after its encounter with host alveolar compartment cells. Our previous studies show that homeostatic, innate soluble components of the alveolar lining fluid (ALF) can quickly alter the cell envelope surface of M.tb upon contact, defining subsequent M.tb –host cell interactions and infection outcomes in vitro and in vivo. We also demonstrated that ALF from 60+ year old elders (E-ALF) vs. healthy 18- to 45-year-old adults (A-ALF) is dysfunctional, with loss of homeostatic capacity and impaired innate soluble responses linked to high local oxidative stress. In this study, a targeted transcriptional assay shows that M.tb exposure to human ALF alters the expression of its cell envelope genes. Specifically, our results indicate that A-ALF-exposed M.tb upregulates cell envelope genes associated with lipid, carbohydrate, and amino acid metabolism, as well as genes associated with redox homeostasis and transcriptional regulators. Conversely, M.tb exposure to E-ALF shows a lesser transcriptional response, with most of the M.tb genes unchanged or downregulated. Overall, this study indicates that M.tb responds and adapts to the lung alveolar environment upon contact, and that the host ALF status, determined by factors such as age, might play an important role in determining infection outcome.
    Keywords Mycobacterium tuberculosis ; alveolar lining fluid (ALF) ; lung mucosa ; cell envelope biosynthesis ; gene expression ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Prospects in Mycobacterium bovis Bacille Calmette et Guérin (BCG) vaccine diversity and delivery: Why does BCG fail to protect against tuberculosis?

    Moliva, Juan I / Joanne Turner / Jordi B. Torrelles

    Vaccine. 2015 Sept. 22, v. 33, no. 39

    2015  

    Abstract: Mycobacterium tuberculosis (M.tb) infection leads to active tuberculosis (TB), a disease that kills one human every 18s. Current therapies available to combat TB include chemotherapy and the preventative vaccine Mycobacterium bovis Bacille Calmette et ... ...

    Abstract Mycobacterium tuberculosis (M.tb) infection leads to active tuberculosis (TB), a disease that kills one human every 18s. Current therapies available to combat TB include chemotherapy and the preventative vaccine Mycobacterium bovis Bacille Calmette et Guérin (BCG). Increased reporting of drug resistant M.tb strains worldwide indicates that drug development cannot be the primary mechanism for eradication. BCG vaccination has been used globally for protection against childhood and disseminated TB, however, its efficacy at protecting against pulmonary TB in adult and aging populations is highly variable. In this regard, the immune response generated by BCG vaccination is incapable of sterilizing the lung post M.tb infection as indicated by the large proportion of individuals with latent TB infection that have received BCG. Although many new TB vaccine candidates have entered the development pipeline, only a few have moved to human clinical trials; where they showed no efficacy and/or were withdrawn due to safety regulations. These trials highlight our limited understanding of protective immunity against the development of active TB. Here, we discuss current vaccination strategies and their impact on the generation and sustainability of protective immunity against TB.
    Keywords adults ; childhood ; clinical trials ; drug resistance ; drug therapy ; humans ; immune response ; Mycobacterium bovis ; Mycobacterium tuberculosis ; sterilizing ; tuberculosis ; vaccination ; vaccines
    Language English
    Dates of publication 2015-0922
    Size p. 5035-5041.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2015.08.033
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: COVID-19 and chronic diabetes

    Genesis P. Aguillón-Durán / Ericka Prieto-Martínez / Doris Ayala / Juan García / John M. Thomas / Juan Ignacio García / Brandon Michael Henry / Jordi B. Torrelles / Joanne Turner / Eder Ledezma-Campos / Blanca I. Restrepo

    Journal of Medical Case Reports, Vol 15, Iss 1, Pp 1-

    the perfect storm for reactivation tuberculosis?: a case series

    2021  Volume 5

    Abstract: Abstract Background The coronavirus disease 2019 pandemic is predicted to have a net negative effect on tuberculosis control, with an estimated excess of 6.3 million tuberculosis cases and 1.4 million deaths by 2025. Programmatic issues such as the ... ...

    Abstract Abstract Background The coronavirus disease 2019 pandemic is predicted to have a net negative effect on tuberculosis control, with an estimated excess of 6.3 million tuberculosis cases and 1.4 million deaths by 2025. Programmatic issues such as the lockdown of tuberculosis services affect all patients, while biosocial factors have a differential impact on an individual’s risk for tuberculosis or adverse tuberculosis outcomes. Case presentation We report three Hispanic cases of incident tuberculosis (two males, 43 and 44 years old; one female, 49 years old) after resolution of coronavirus disease episodes. Coincidentally, all cases shared a common risk factor: a chronic history poorly controlled diabetes. Conclusions Our findings alert to the threat posed by the synergy between coronavirus disease and diabetes, on tuberculosis reactivation. In medium- to high-risk settings for tuberculosis, we recommend implementation of routine screening for latent tuberculosis infection in these cases, and preventive tuberculosis treatment in those who are positive.
    Keywords Tuberculosis ; COVID-19 ; SARS-CoV-2 ; Diabetes mellitus ; Type 2 diabetes ; Diagnostic delays ; Medicine ; R
    Subject code 572
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A prospective cross-sectional study of tuberculosis in elderly Hispanics reveals that BCG vaccination at birth is protective whereas diabetes is not a risk factor.

    Julia M Scordo / Génesis P Aguillón-Durán / Doris Ayala / Ana Paulina Quirino-Cerrillo / Eminé Rodríguez-Reyna / Francisco Mora-Guzmán / Jose A Caso / Eder Ledezma-Campos / Larry S Schlesinger / Jordi B Torrelles / Joanne Turner / Blanca I Restrepo

    PLoS ONE, Vol 16, Iss 7, p e

    2021  Volume 0255194

    Abstract: Background Aging increases the risk of tuberculosis (TB) and its adverse outcomes, but most studies are based on secondary analyses, and few are in Hispanics. Diabetes is a risk factor for TB in adults, but its contribution in the elderly is unknown. We ... ...

    Abstract Background Aging increases the risk of tuberculosis (TB) and its adverse outcomes, but most studies are based on secondary analyses, and few are in Hispanics. Diabetes is a risk factor for TB in adults, but its contribution in the elderly is unknown. We aimed to identify the role of diabetes and other risk factors for TB in elderly Hispanics. Methods Cross-sectional study among newly-diagnosed TB patients, recent contacts (ReC), or community controls (CoC) totaling 646 participants, including 183 elderly (>60 years; 43 TB, 80 ReC, 60 CoC) and 463 adults (18 to 50 years; 80 TB, 301 ReC and 82 CoC). Host characteristics associated with TB and latent Mycobacterium tuberculosis infection (LTBI) were identified in the elderly by univariable and confirmed by multivariable logistic regression. Results LTBI was more prevalent among the elderly CoC (55% vs. 23.2% in adults; p<0.001), but not in ReC (elderly 71.3% vs. adult 63.8%); p = 0.213). Risk factors for TB in the elderly included male sex (adj-OR 4.33, 95% CI 1.76, 10.65), smoking (adj-OR 2.55, 95% CI 1.01, 6.45) and low BMI (adj-OR 12.34, 95% CI 4.44, 34.33). Unexpectedly, type 2 diabetes was not associated with TB despite its high prevalence (adj-OR 0.38, 95% CI 0.06, 2.38), and BCG vaccination at birth was protective (adj-OR 0.16, 95% CI 0.06, 0.45). Conclusions We report novel distinctions in TB risk factors in the elderly vs. adults, notably in diabetes and BCG vaccination at birth. Further studies are warranted to address disparities in this vulnerable, understudied population.
    Keywords Medicine ; R ; Science ; Q
    Subject code 338
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Modeling SARS-CoV-2 and influenza infections and antiviral treatments in human lung epithelial tissue equivalents

    Hoda Zarkoob / Anna Allué-Guardia / Yu-Chi Chen / Andreu Garcia-Vilanova / Olive Jung / Steven Coon / Min Jae Song / Jun-Gyu Park / Fatai Oladunni / Jesse Miller / Yen-Ting Tung / Ivan Kosik / David Schultz / James Iben / Tianwei Li / Jiaqi Fu / Forbes D. Porter / Jonathan Yewdell / Luis Martinez-Sobrido /
    Sara Cherry / Jordi B. Torrelles / Marc Ferrer / Emily M. Lee

    Communications Biology, Vol 5, Iss 1, Pp 1-

    2022  Volume 17

    Abstract: Human alveolar and tracheobronchial epithelial air liquid interface (ALI) tissues are used as models to examine cellular responses to SARS-CoV-2 and influenza A virus infections and as antiviral drug screening assay platforms. ...

    Abstract Human alveolar and tracheobronchial epithelial air liquid interface (ALI) tissues are used as models to examine cellular responses to SARS-CoV-2 and influenza A virus infections and as antiviral drug screening assay platforms.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Modifications of Pseudomonas aeruginosa cell envelope in the cystic fibrosis airway alters interactions with immune cells

    Preston J. Hill / Julia M. Scordo / Jesús Arcos / Stephen E. Kirkby / Mark D. Wewers / Daniel J. Wozniak / Jordi B. Torrelles

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 10

    Abstract: Abstract Pseudomonas aeruginosa is a ubiquitous environmental organism and an opportunistic pathogen that causes chronic lung infections in the airways of cystic fibrosis (CF) patients as well as other immune-compromised individuals. During infection, P. ...

    Abstract Abstract Pseudomonas aeruginosa is a ubiquitous environmental organism and an opportunistic pathogen that causes chronic lung infections in the airways of cystic fibrosis (CF) patients as well as other immune-compromised individuals. During infection, P. aeruginosa enters the terminal bronchioles and alveoli and comes into contact with alveolar lining fluid (ALF), which contains homeostatic and antimicrobial hydrolytic activities, termed hydrolases. These hydrolases comprise an array of lipases, glycosidases, and proteases and thus, they have the potential to modify lipids, carbohydrates and proteins on the surface of invading microbes. Here we show that hydrolase levels between human ALF from healthy and CF patients differ. CF-ALF influences the P. aeruginosa cell wall by reducing the content of one of its major polysaccharides, Psl. This CF-ALF induced Psl reduction does not alter initial bacterial attachment to surfaces but reduces biofilm formation. Importantly, exposure of P. aeruginosa to CF-ALF drives the activation of neutrophils and triggers their oxidative response; thus, defining human CF-ALF as a new innate defense mechanism to control P. aeruginosa infection, but at the same time potentially adding to the chronic inflammatory state of the lung in CF patients.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2017-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Checks and Balances between Autophagy and the Inflammasomes during Infection

    Seveau, Stephanie / Amal O. Amer / Jacob Yount / Joanne Turner / Jordi B. Torrelles / Luanne Hall-Stoodley / Mikhail A. Gavrilin

    Journal of Molecular Biology. 2017,

    2017  

    Abstract: Autophagy and inflammasome complex assembly are physiological processes that control homeostasis, inflammation, and immunity. Autophagy is a ubiquitous pathway that degrades cytosolic macromolecules or organelles, as well as intracellular pathogens. ... ...

    Abstract Autophagy and inflammasome complex assembly are physiological processes that control homeostasis, inflammation, and immunity. Autophagy is a ubiquitous pathway that degrades cytosolic macromolecules or organelles, as well as intracellular pathogens. Inflammasomes are multi-protein complexes that assemble in the cytosol of cells upon detection of pathogen- or danger-associated molecular patterns. A critical outcome of inflammasome assembly is the activation of the serine protease caspase-1, which activates the pro-inflammatory cytokine precursors pro-IL-1β and pro-IL-18. Studies on chronic inflammatory diseases, heart diseases, Alzheimer’s disease, and multiple sclerosis revealed that autophagy and inflammasomes intersect and regulate each other. In the context of infectious diseases, however less is known about the interplay between autophagy and inflammasome assembly, though it is becoming evident that pathogens have evolved multiple strategies to inhibit and/or subvert these pathways and to take advantage of their intricate crosstalk. An improved appreciation of these pathways and their subversion by diverse pathogens is expected to help in the design of anti-infective therapeutic interventions.
    Keywords Alzheimer disease ; autophagy ; caspase-1 ; cytokines ; cytosol ; heart diseases ; homeostasis ; infectious diseases ; inflammasomes ; inflammation ; organelles ; pathogens ; sclerosis ; serine proteinases
    Language English
    Size p. .
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2017.11.006
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Evaluation of Mycobacterium tuberculosis lipoarabinomannan antigen assay and rapid serology blood test for the diagnosis of bovine tuberculosis in Ethiopia

    Aboma Zewude / Temesgen Mohammed / Lemma Terfassa / W. Garrett Hunt / Xueliang Pan / Joan Miquel Balada-Llasat / Wondwossen Gebreyes / Jordi B. Torrelles / Shu-Hua Wang / Gobena Ameni

    BMC Veterinary Research, Vol 15, Iss 1, Pp 1-

    2019  Volume 8

    Abstract: Abstract Background Bovine tuberculosis (bTB) is prevalent in dairy cattle in Ethiopia. Currently used diagnostic tools such as the single intradermal comparative tuberculin test (SICTT) are time consuming and labor intensive. A rapid, easy-to-use and ... ...

    Abstract Abstract Background Bovine tuberculosis (bTB) is prevalent in dairy cattle in Ethiopia. Currently used diagnostic tools such as the single intradermal comparative tuberculin test (SICTT) are time consuming and labor intensive. A rapid, easy-to-use and cost-effective diagnostic test would greatly contribute to the control of bTB in developing countries like Ethiopia. In the present study, two point-of-care diagnostic tests were evaluated for the detection of bTB: LIONEX® Animal TB Rapid test, a membrane-based test for the detection of antibodies to Mycobacterium bovis in blood and ALERE® Determine TB Lipoarabinomannan (LAM) Ag, an immunoassay for the detection of lipoarabinomannan (LAM) antigen (Ag) of mycobacteria in urine. A combination of the SICTT and gamma interferon (IFN-γ) test was used as the gold standard for the validation of these point-of-care tests, as it was not feasible to slaughter the study animals to carry out the historical gold standard of mycobacterial culture. A total of 175 heads of cattle having three different bTB infection categories (positive SICTT, negative SICTT, and unknown SICTT status) were used for this study. Result The sensitivity and specificity of TB LAM Ag were 72.2% (95% CI = 62.2, 80.4) and 98.8% (95% CI = 93.6, 99.7), respectively, while the sensitivity and specificity of the LIONEX Animal TB rapid test assay were 54% (95% CI = 44.1 64.3) and 98.8% (95% CI = 93.6, 99.7) respectively. The agreement between TB LAM Ag and SICTT was higher (κ = 0.85; 95% CI = 0.65–0.94) than between TB LAM Ag and IFN-γ (κ = 0.67; 95% CI = 0.52–0.81). The agreement between LIONEX Animals TB Rapid blood test and SICTT was substantial, (κ = 0.63; 95% CI = 0.49–0.77) while the agreement between LIONEX Animal TB rapid blood test and IFN-γ test was moderate (κ = 0.53; 95% CI = 0.40–0.67). Analysis of receiver operating curve (ROC) indicated that the area under the ROC curve (AUC) for TB LAM Ag was 0.85 (95% CI = 0.79–0.91) while it was 0.76 (95% CI; =0.69–0.83) for LIONEX Animal TB rapid test assay. Conclusion This study showed that TB LAM Ag had a better diagnostic performance and could potentially be used as ancillary either to SICTT or IFN-γ test for diagnosis of bTB.
    Keywords TB LAM antigen ; LIONEX animal TB rapid ; Bovine tuberculosis ; Diagnostic performance ; Ethiopia ; Veterinary medicine ; SF600-1100
    Subject code 630
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Immunogenicity and protective efficacy of an intranasal live-attenuated vaccine against SARS-CoV-2

    Jun-Gyu Park / Fatai S. Oladunni / Mohammed A. Rohaim / Jayde Whittingham-Dowd / James Tollitt / Matthew D.J. Hodges / Nadin Fathallah / Muhsref Bakri Assas / Wafaa Alhazmi / Abdullah Almilaibary / Munir Iqbal / Pengxiang Chang / Renee Escalona / Vinay Shivanna / Jordi B. Torrelles / John J. Worthington / Lucy H. Jackson-Jones / Luis Martinez-Sobrido / Muhammad Munir

    iScience, Vol 24, Iss 9, Pp 102941- (2021)

    2021  

    Abstract: Summary: Global deployment of an effective and safe vaccine is necessary to curtail the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a Newcastle disease virus (NDV)-based ... ...

    Abstract Summary: Global deployment of an effective and safe vaccine is necessary to curtail the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a Newcastle disease virus (NDV)-based vectored-vaccine in mice and hamsters for its immunogenicity, safety, and protective efficacy against SARS-CoV-2. Intranasal administration of recombinant (r)NDV-S vaccine expressing spike (S) protein of SARS-CoV-2 to mice induced high levels of SARS-CoV-2-specific neutralizing immunoglobulin A (IgA) and IgG2a antibodies and T-cell-mediated immunity. Hamsters immunized with two doses of vaccine showed complete protection from lung infection, inflammation, and pathological lesions following SARS-CoV-2 challenge. Importantly, administration of two doses of intranasal rNDV-S vaccine significantly reduced the SARS-CoV-2 shedding in nasal turbinate and lungs in hamsters. Collectively, intranasal vaccination has the potential to control infection at the site of inoculation, which should prevent both clinical disease and virus transmission to halt the spread of the COVID-19 pandemic.
    Keywords immunology ; virology ; Science ; Q
    Subject code 630
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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