Review
Infectious Diseases
David F. Woods, Stephanie Flynn, Jose A. Caparros-Martin, Stephen M. Stick, F. Jerry Reen, Fergal O'Gara
Summary: The imbalance in respiratory microbiota can lead to lung disease pathogenesis, with bile acids playing a key role in CF cases, associated with inflammation and restructuring of lung microbiota towards a pathogen-dominated state.
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)
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
Biochemistry & Molecular Biology
Javier Macho Rendon, Rocio Rebollido-Rios, Marc Torrent Burgas
Summary: Protein-protein interactions play important roles in cellular processes. To address the limited knowledge of host-pathogen interactomes, we developed HPIPred, a numerical encoding-based host-pathogen PPI prediction tool. Through screening the entire proteomes of Homo sapiens and Pseudomonas aeruginosa PAO1, we generated a highly connected network topology of host-pathogen interactome using HPIPred.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
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
Infectious Diseases
Margherita Degasperi, Riccardo Sgarra, Mario Mardirossian, Sabrina Pacor, Massimo Maschio, Marco Scocchi
Summary: This study developed a prodrug to extend the peptide chain of an antimicrobial peptide and added a sequence that can activate the peptide at the site of infection/inflammation, enabling a slow and targeted release. The prodrug showed good antimicrobial activity and lower cytotoxicity in the presence of elastase.
Article
Pediatrics
Noel Gonzalez-Rosales, Ajay S. S. Kasi, Courtney E. E. McCracken, George L. L. Silva, Miah Starks, Arlene Stecenko, Lokesh Guglani
Summary: In pediatric patients with cystic fibrosis, one-third of pulmonary exacerbations requiring hospitalization were associated with viral infections, with rhinovirus/enterovirus being the most common. Viral-positive pulmonary exacerbations did not lead to a greater decline or delayed recovery of lung function, increased risk for Pseudomonas aeruginosa acquisition, or higher frequency of subsequent exacerbations.
PEDIATRIC PULMONOLOGY
(2023)
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
Gabriele Sass, Julianne J. Marsh, Pallabi Shrestha, Raquel Sabino, David A. Stevens
Summary: Cystic fibrosis patients frequently suffer from co-infections of Pseudomonas aeruginosa and Aspergillus fumigatus, which can cause airway inflammation and worsen lung function. Recent studies have shown that P. aeruginosa interacts synergistically with the antifungal drug voriconazole, inhibiting A. fumigatus biofilm metabolism. This interaction is mediated by several molecules, including pyoverdine. Clinical isolates of P. aeruginosa from CF patients show varying degrees of interaction with voriconazole, suggesting that lower concentrations of the drug might be sufficient to control fungal growth during co-infections.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
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
Katrin Anne Becker, Rabea Verhaegh, Hedda-Luise Verhasselt, Simone Keitsch, Matthias Soddemann, Barbara Wilker, Gregory C. Wilson, Jan Buer, Syed A. Ahmad, Michael J. Edwards, Erich Gulbins
Summary: Genetic overexpression of acid ceramidase in cystic fibrosis mice increases immunity and protects against pulmonary infections with P. aeruginosa. Sphingosine has been shown to effectively kill pathogenic bacteria. Normalizing sphingosine levels in airway epithelial cells can prevent infections in cystic fibrosis patients.
INFECTION AND IMMUNITY
(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
Infectious Diseases
Kim Thomsen, Lars Christophersen, Christian Johann Lerche, Dennis Back Holmgaard, Henrik Calum, Niels Hoiby, Claus Moser
Summary: The combination of azithromycin and anti-Pseudomonas IgY therapy enhances bacterial killing and pulmonary elimination of P. aeruginosa, leading to a decrease in inflammatory markers and potential clinical application for improving anti-Pseudomonas strategies.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Pediatrics
Christine Ronne Hansen, Marita Gilljam, Hanne V. Olesen, Niels Hoiby, Ferenc Karpati, Ewa Johansson, Christina Krantz, Marianne Skov, Tacjana Pressler, Anders Lindblad
Review
Microbiology
Oana Ciofu, Claus Moser, Peter Ostrup Jensen, Niels Hoiby
Summary: Chronic infections caused by microbial biofilms pose a significant clinical challenge due to the resistance of biofilms to antimicrobials and the immune system, leading to persistent and recurrent infections. This Review discusses the current understanding of the mechanisms underlying the tolerance of biofilms to the immune system and to antimicrobials, as well as their role in the development of antimicrobial resistance.
NATURE REVIEWS MICROBIOLOGY
(2022)
Article
Infectious Diseases
Anne Sofie Laulund, Franziska Angelika Schwartz, Lars Christophersen, Niels Hoiby, John Sigurd Mjoen Svendsen, Wenche Stensen, Kim Thomsen, Jorunn Pauline Cavanagh, Claus Moser
Summary: This study aimed to investigate whether adjunctive AMC-109 could augment the ciprofloxacin effect in a chronic Pseudomonas aeruginosa wound model. The results showed that the combined treatment group had a lower bacterial load, decreased pro-inflammatory response, and improved tissue remodeling.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Immunology
Franziska A. Schwartz, Luna Nielsen, Struve Jessica Andersen, Magnus Bock, Lars Christophersen, Torgny Sunnerhagen, Christian Johann Lerche, Lene Bay, Henning Bundgaard, Niels Hoiby, Claus Moser
Summary: This study aimed to further characterize the time course of biofilm formation and the impact on antibiotic tolerance development. The findings indicate that both a Staphylococcus aureus reference strain and three clinical IE isolates formed biofilms on the IEV after 6 hours.
Article
Ecology
Adela M. Lujan, Steve Paterson, Elze Hesse, Lea M. Sommer, Rasmus L. Marvig, M. D. Sharma, Ellinor O. Alseth, Oana Ciofu, Andrea M. Smania, Soren Molin, Helle Krogh Johansen, Angus Buckling
Summary: Co-infecting pathogens can influence the selection of Pseudomonas aeruginosa mutators, limiting their fixation. This study is important for understanding bacterial evolution in chronic infections.
NATURE ECOLOGY & EVOLUTION
(2022)
Article
Immunology
Hong Wu, Lulu Song, Joey Kuok Hoong Yam, Marian Plotkin, Hengzhuang Wang, Morten Rybtke, Dror Seliktar, Theodoros Kofidis, Niels Hoiby, Tim Tolker-Nielsen, Zhijun Song, Michael Givskov
Summary: The study investigated the development and study of Pseudomonas aeruginosa biofilms using PF hydrogel material in vitro and in vivo. The results showed that the biofilms formed typical structures in the PF hydrogel and were tolerant to antibiotics and host immune response. The PF hydrogel biofilm model is simple and has various applications.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Franziska A. Schwartz, Lars Christophersen, Kim Thomsen, Sarah Baekdal, Maria Pals Bendixen, Mette Jorgensen, Ida Kirstine Bull Rasmussen, Anne Sofie Laulund, Niels Hoiby, Claus Moser
Summary: Passive intravesical administration of avian egg yolk anti-Pseudomonas antibodies (IgY) may be a novel strategy to prevent urinary tract infections with Pseudomonas aeruginosa.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Eva Armengol, Kasper Norskov Kragh, Tim Tolker-Nielsen, Josep M. Sierra, Doaa Higazy, Oana Ciofu, Miguel Vinas, Niels Hoiby
Summary: The combination of colistin and rifampicin has been found to effectively kill colistin-resistant Pseudomonas aeruginosa, suggesting it as a promising treatment for infections caused by this strain.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Immunology
Magnus Bock, Anna Marie Theut, Johan G. C. van Hasselt, Hengzhuang Wang, Kurt Fuursted, Niels Hoiby, Christian Johann Lerche, Nikolaj Ihlemann, Sabine Gill, Ulrik Christiansen, Hans Linde Nielsen, Lars Lemming, Hanne Elming, Jonas A. Povlsen, Niels Eske Bruun, Dan Hofsten, Emil L. Fosbol, Lars Kober, Martin Schultz, Mia M. Pries-Heje, Jonas Henrik Kristensen, Jens Jorgen Christensen, Flemming S. Rosenvinge, Christian Torp Pedersen, Jannik Helweg-Larsen, Niels Tonder, Kasper Iversen, Henning Bundgaard, Claus Moser
Summary: Pharmacokinetic/pharmacodynamic analyses were conducted to assess the probabilities of target attainment for oral treatments of infective endocarditis. The majority of patients achieved the target level with orally administered antibiotics, supporting the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Magnus Bock, Johan G. C. Van Hasselt, Franziska Schwartz, Hengzhuang Wang, Niels Hoiby, Kurt Fuursted, Nikolaj Ihlemann, Sabine Gill, Ulrik Christiansen, Niels Eske Bruun, Hanne Elming, Jonas A. Povlsen, Lars Kober, Dan E. Hofsten, Emil L. Fosbol, Mia M. Pries-Heje, Jens Jorgen Christensen, Flemming S. Rosenvinge, Christian Torp-Pedersen, Jannik Helweg-Larsen, Niels Tonder, Kasper Iversen, Henning Bundgaard, Claus Moser
Summary: This study characterized the population pharmacokinetics of linezolid in patients with infective endocarditis and found that there is a substantial interaction between linezolid and rifampicin, which increases the clearance of linezolid. Model-based simulations showed that increasing the linezolid dose can compensate for the interaction without increasing the risk of adverse effects.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Microbiology
Anne Sofie Laulund, Franziska Angelika Schwartz, Lars Christophersen, Mette Kolpen, Peter Ostrup Jensen, Henrik Calum, Niels Hoiby, Kim Thomsen, Claus Moser
Summary: Chronic wounds have compromised microcirculation and are often infested with microorganisms in biofilms, hindering antibiotic function. This study investigates whether hyperbaric oxygen therapy (HBOT) can counteract this process.
Article
Microbiology
Anne Sofie Laulund, Franziska Angelika Schwartz, Niels Hoiby, Kim Thomsen, Claus Moser
Summary: The study demonstrates that hyperbaric oxygen therapy (HBOT) can enhance the effectiveness of tobramycin in biofilms and counteract the micro-compartmentalization of biofilm pharmacokinetics through increased available tobramycin and augmented bacterial killing.
Article
Immunology
Renan Marrichi Mauch, Peter ostrup Jensen, Tavs Qvist, Mette Kolpen, Claus Moser, Tacjana Pressler, Marcos Tadeu Nolasco da Silva, Niels Hoiby, Copenhagen Study Grp Mycobacterial Infect Cyst Fibrosis
Summary: This study aimed to investigate the adaptive immune response to Mycobacterium abscessus complex (MABSC) and its cross-reactivity with Mycobacterium avium complex (MAC) and Mycobacterium bovis (BCG) in cystic fibrosis (CF) patients and non-CF controls. The results showed a similar immune response pattern in CF patients with MABSC and BCG-vaccinated controls, suggesting cross-reactivity. Importance: 6/10.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)