Review
Physiology
Nicole Reyne, Alexandra McCarron, Patricia Cmielewski, David Parsons, Martin Donnelley
Summary: Cystic fibrosis lung disease is caused by recurrent bacterial infections, particularly Pseudomonas aeruginosa. Current animal models do not fully replicate the human disease, including environmental pathogen colonization. Delivering bacteria in different forms to the lungs of animals can model cystic fibrosis bacterial lung infections. Developing more accurate lung infection models has the potential to advance understanding and treatment of cystic fibrosis lung disease.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Microbiology
Samantha L. Durfey, Sudhakar Pipavath, Anna Li, Anh T. Vo, Anina Ratjen, Suzanne Carter, Sarah J. Morgan, Matthew C. Radey, Brenda Grogan, Stephen J. Salipante, Michael J. Welsh, David A. Stoltz, Christopher H. Goss, Edward F. McKone, Pradeep K. Singh
Summary: Studies show that chronic CF infections may persist despite improvements induced by CFTR modulators and aggressive antibiotic treatment. Combining CFTR modulators with intensive antibiotics may be most effective for patients with higher CFTR activity. Challenges remain in improving the health of people with CF.
Article
Immunology
Manon Ruffin, Jeanne Bigot, Claire Calmel, Julia Mercier, Maelle Givelet, Justine Oliva, Andres Pizzorno, Manuel Rosa-Calatrava, Harriet Corvol, Viviane Balloy, Olivier Terrier, Loic Guillot
Summary: In this study, it was found that Pseudomonas aeruginosa increases the expression of TMPRSS2 in airway epithelial cells and Calu-3 cells, potentially enhancing susceptibility to SARS-CoV-2 infection. The mechanism is through the activation of Toll-like receptor-5 and p38 MAPK. This result may have clinical significance for cystic fibrosis patients who are frequently infected with P. aeruginosa.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Dirk Westhoelter, Jonas Raspe, Hendrik Uebner, Johannes Pipping, Mona Schmitz, Svenja Strassburg, Sivagurunathan Sutharsan, Matthias Welsner, Christian Taube, Sebastian Reuter
Summary: The study found that treatment with elexacaftor/tezacaftor/ivacaftor can increase the percentage of Tregs, especially in CF patients clearing Pseudomonas aeruginosa infection. This suggests that targeting Treg homeostasis is a therapeutic option for CF patients with persistent Treg impairment.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Microbiology
Christina S. Thornton, Michael G. Surette
Summary: Cystic fibrosis is the most common and lethal genetic disease among the Caucasian population, leading to chronic airway inflammation and declining pulmonary function. Studies have shown a diverse community of anaerobic bacteria in CF patients' airways, potentially impacting disease progression through synergistic interaction with principal pathogens. Despite the understanding of this complex bacterial milieu, the specific roles of anaerobes in disease progression remain unclear.
JOURNAL OF CLINICAL MICROBIOLOGY
(2021)
Article
Microbiology
Xuerui Bao, Mona Bove, Tom Coenye
Summary: The high tolerance of Pseudomonas aeruginosa biofilms in respiratory tract infections in cystic fibrosis contributes to the failure of antibiotic therapy. This study identified carbon sources that could enhance the inhibiting and/or eradicating activity of tobramycin, ciprofloxacin, and ceftazidime against P. aeruginosa PAO1 biofilms. The mechanisms underlying the enhanced biofilm eradicating activity were strain-dependent.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Review
Immunology
Veronica Roxana Flores-Vega, Silvia Yalid Vargas-Roldan, Jose Luis Lezana-Fernandez, Ricardo Lascurain, Jose Ignacio Santos-Preciado, Roberto Rosales-Reyes
Summary: Cystic fibrosis is a genetic disease caused by a mutation in the cftr gene, affecting chloride ion and water transport and leading to bacterial infections in the lungs. Autophagy plays a crucial role in pathogen clearance, but P. aeruginosa and B. cenocepacia have strategies to evade this pathway, resulting in chronic inflammatory immune responses.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Patrick J. Stapleton, Conrad Izydorcyzk, Shawn Clark, Ana Blanchard, Pauline W. Wang, Yvonne Yau, Valerie Waters, David S. Guttman
Summary: In early CF infections, there is evidence of P. aeruginosa strain-sharing, with some infections likely being transmitted between patients. Mixed-strain infections are associated with strain-sharing, but strain-sharing does not impact antibiotic eradication treatment failure rates.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Immunology
Jonathan D. Cogen, Anna Faino, Frankline Onchiri, Lucas R. Hoffman, Matthew P. Kronman, David P. Nichols, Margaret Rosenfeld, Ronald L. Gibson
Summary: A retrospective cohort study found that there were no significant differences in respiratory and clinical outcomes between young patients with cystic fibrosis treated with one versus two intravenous antipseudomonal antibiotics for pulmonary exacerbations.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Giovanni Di Bonaventura, Veronica Lupetti, Simone De Fabritiis, Alessandra Piccirilli, Annamaria Porreca, Marta Di Nicola, Arianna Pompilio
Summary: This study evaluated the antibacterial and antivirulence activities of eight FDA-approved non-antibiotic drugs and their effects on biofilm formation. Ciclopirox and actinomycin D showed the best antibacterial activity and were most effective against preformed biofilms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Medicine, Research & Experimental
Roberto Rosales-Reyes, Veronica Roxana Flores-Vega, Jose Luis Lezana-Fernandez, Jose Ignacio Santos-Preciado
Summary: Pseudomonas aeruginosa is a significant pathogen causing lung infections in patients with cystic fibrosis. Its increasing antibiotic resistance makes treatment challenging. Microbiology and whole genome sequencing are important tools for determining antimicrobial susceptibility and resistance as well as analyzing genomic variations. Molecular epidemiologic surveillance aids in developing better treatment strategies and controlling the spread of Pseudomonas aeruginosa variants.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Immunology
Jonathan D. Cogen, Frankline M. Onchiri, Nicole Mayer Hamblett, Ronald L. Gibson, Wayne J. Morgan, Margaret Rosenfeld
Summary: The study showed that prolonged use of oral antibiotics in children with cystic fibrosis increased the risk of acquiring Achromobacter xylosoxidans, while treatment with intravenous antibiotics was associated with an increased risk of acquiring multidrug-resistant Pseudomonas aeruginosa and MRSA.
CLINICAL INFECTIOUS DISEASES
(2021)
Review
Biochemistry & Molecular Biology
Carla M. P. Ribeiro, Matthew G. Higgs, Marianne S. Muhlebach, Matthew C. Wolfgang, Monica Borgatti, Ilaria Lampronti, Giulio Cabrini
Summary: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have provided a significant therapeutic advantage for people with cystic fibrosis (pwCF). However, these modulators face limitations in reducing chronic lung bacterial infection and inflammation, which are the main causes of respiratory damage and insufficiency in pwCF, especially in adults. This article revisits the debated issues of pulmonary bacterial infection and inflammatory processes in pwCF, highlighting the mechanisms favoring bacterial infection, the interplay between Pseudomonas aeruginosa and Staphylococcus aureus, and the cross-talk among bacteria, bronchial epithelial cells, and host immune defenses. The recent findings on the effect of CFTR modulators on bacterial infection and inflammation are also presented to identify potential therapeutic targets for respiratory pathology in pwCF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Angela Sandri, Janus Anders Juul Haagensen, Laura Veschetti, Helle Krogh Johansen, Soren Molin, Giovanni Malerba, Caterina Signoretto, Marzia Boaretti, Maria M. Lleo
Summary: In patients with cystic fibrosis, the main pathogen Pseudomonas aeruginosa often coexists with other microbes in the lungs, potentially affecting clinical outcomes. While some Achromobacter spp. isolates can inhibit P. aeruginosa biofilm formation, different strains of Achromobacter spp. may exhibit either competition or cohabitation with co-isolated P. aeruginosa strains during long-term co-infections. Genetic variants supporting higher virulence were found in a competitive Achromobacter sp. isolate, indicating the possible evolution of interplays during chronic infections.
Article
Microbiology
Giovanni Di Bonaventura, Veronica Lupetti, Fabio Verginelli, Sara Giancristofaro, Rosemary Barbieri, Giovanni Gherardi, Arianna Pompilio
Summary: This study evaluated the antibacterial, antibiofilm, and antivirulence activities of apramycin compared to tobramycin against P. aeruginosa in cystic fibrosis patients. Apramycin showed better efficacy than tobramycin, without cytotoxicity to bronchial epithelial CF cells.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Cell Biology
Sonia Brun, Eloine Bestion, Eric Raymond, Firas Bassissi, Zuzana Macek Jilkova, Soraya Mezouar, Madani Rachid, Marie Novello, Jennifer Tracz, Ahmed Hamai, Gilles Lalmanach, Lise Vanderlynden, Raphael Legouffe, Jonathan Stauber, Thomas Schubert, Maximilian G. Plach, Jerome Courcambeck, Cyrille Drouot, Guillaume Jacquemot, Cindy Serdjebi, Gael Roth, Jean-Pierre Baudoin, Christelle Ansaldi, Thomas Decaens, Philippe Halfon
Summary: The new autophagy inhibitor GNS561 shows high liver tropism and potent antitumor activity, particularly against hepatocellular carcinoma. Its mechanism of action involves lysosomal disruption and induction of cell death in tumor cells.
Article
Biochemistry & Molecular Biology
J. Sage, J. Renault, R. Domain, K. K. Bojarski, T. Chazeirat, A. Saidi, E. Leblanc, C. Nizard, S. A. Samsonov, R. Kurfurst, G. Lalmanach, F. Lecaille
Summary: This study identified neohesperidin dihydrochalcone (NHDC) as a potent inhibitor of cathepsin S (Cat S), which plays a role in the degradation of extracellular-matrix and basement membrane. NHDC inhibited the hydrolysis of key proteins in the basement membrane and reduced the expression and activity of Cat S in human keratinocytes. Furthermore, NHDC increased the expression of the anti-inflammatory cytokine IL-10 and mediated the STAT3 signaling pathway, leading to the suppression of Cat S expression.
Article
Biochemistry & Molecular Biology
Emilia Ilowska, Jakub Barciszewski, Mariusz Jaskolski, Augustyn Molinski, Maciej Kozak, Aneta Szymanska
Summary: Amyloid fibrils, known for their negative association with amyloid diseases, hold potential as nanomaterials due to their stability, storage capacity, and controlled release of active peptides. They can be utilized in drug delivery systems and easily modified. This research focuses on the discovery of steric zipper-forming peptides in amyloidogenic protein, human cystatin C, and the factors influencing their fibrillar structure formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
K. K. Bojarski, J. Sage, G. Lalmanach, F. Lecaille, S. A. Samsonov
Summary: This study investigated the interactions between human cysteine cathepsins and various types of glycosaminoglycans (GAGs). Molecular docking simulations and molecular dynamics analysis revealed that electrostatics play a crucial role in driving the cathepsin-GAG interactions, and the length of GAG chains significantly affects the strength of these interactions. Furthermore, binding of GAGs at different regions on cathepsins surface has varying effects on the enzymatic activity, depending on the cathepsin and GAG type.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Article
Chemistry, Applied
Sophie Denamur, Thibault Chazeirat, Martyna Maszota-Zieleniak, Romain R. Vives, Ahlame Saidi, Fuming Zhang, Robert J. Linhardt, Francois Labarthe, Sergey A. Samsonov, Gilles Lalmanach, Fabien Lecaille
Summary: The levels of human cystatin C (hCC) were found to be elevated in respiratory specimens from MPS patients and correlated with severe respiratory symptoms. Heparan sulfate (HS) was shown to reduce the inhibitory activity of hCC towards cathepsin L. Molecular modeling studies identified three regions in hCC that bind tightly to HS.
CARBOHYDRATE POLYMERS
(2022)
Article
Biochemistry & Molecular Biology
Iga Biskupek, Cezary Czaplewski, Justyna Sawicka, Emilia Ilowska, Maria Dzierzynska, Sylwia Rodziewicz-Motowidlo, Adam Liwo
Summary: The UNited RESidue (UNRES) model was used to study the aggregation behavior of 20 peptides with different lengths. The majority of peptides showed inter-strand beta-sheet formation, except for glutamine- and asparagine-rich peptides, which require modification of the UNRES model.
Article
Infectious Diseases
Oktawian Stachurski, Damian Neubauer, Aleksandra Walewska, Emilia Ilowska, Marta Bauer, Sylwia Bartoszewska, Karol Sikora, Aleksandra Hac, Dariusz Wyrzykowski, Adam Prahl, Wojciech Kamysz, Emilia Sikorska
Summary: This study investigates short cationic antimicrobial lipopeptides with a high propensity to fibrillate, which exhibit high activity and stability on bacterial membranes, and low cytotoxicity against human cells. The findings suggest that monomers are the main active form and the target of action of the lipopeptides is the bacterial membrane.
Review
Biochemistry & Molecular Biology
Fabien Lecaille, Thibault Chazeirat, Ahlame Saidi, Gilles Lalmanach
Summary: This review discusses the role of human cysteine cathepsin V in various biological and pathophysiological processes. It provides an overview of the molecular aspects, including genomic organization, protein structure, and substrate specificity. The dysregulation of cathepsin V expression and activity is related to the progression of malignancies and vascular disorders. The article highlights the potential of cathepsin V as a therapeutic target.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Multidisciplinary Sciences
Edyta Proniewicz, Grzegorz Burnat, Helena Domin, Adam Roman, Adam Prahl, Emilia Llowska
Summary: This study synthesized multiple analogs of bradykinin and examined their biological activity on cell lines expressing B1 or B2 receptors. The mRNA expression of B1R and B2R in tumor cell lines was also determined. In addition, the adsorption of five B1R antagonists at the liquid/solid interface was discussed.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Paul Bigot, Simon Chesseron, Ahlame Saidi, Damien Sizaret, Christelle Parent, Agnes Petit-Courty, Yves Courty, Fabien Lecaille, Gilles Lalmanach
Summary: Chronic obstructive pulmonary disease (COPD) is an irreversible disease mainly caused by smoking. The protein occludin, involved in the cohesion of epithelial tight junctions, is found to be decreased in lung biopsies of smokers and correlates with smoking history, COPD grades, and cathepsin S (CatS) activity. Cigarette smoke-elicited CatS induces an alteration of epithelial integrity via the proteolytic injury of occludin, highlighting the emerging role of CatS in smoking-related lung diseases and the relevance of targeting CatS in the treatment of emphysema and COPD.
Article
Biochemistry & Molecular Biology
Magdalena Szarynska, Agata Olejniczak-Keder, Kamila Podplonska, Adam Prahl, Emilia Ilowska
Summary: This study analyzed the influence of chemical modifications on the properties of two peptides (BK and NT) related to colorectal cancer, and identified a group of modified peptides that showed potential in reducing cancer cell count and tumor stem cell content.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Alexis David, Thibault Chazeirat, Ahlame Saidi, Gilles Lalmanach, Fabien Lecaille
Summary: Mucopolysaccharidosis (MPS) is a group of inherited lysosomal storage disorders caused by enzyme defects in glycosaminoglycan (GAG) metabolism. Accumulation of GAGs leads to tissue dysfunctions during childhood, resulting in premature death. Understanding the molecular mechanisms and exploring the role of cysteine cathepsins in MPS may improve current therapies. This review summarizes the current understanding of MPS disorders, their management, and the interplay between GAGs and cysteine cathepsins.