Article
Microbiology
Madeline Mei, Preston Pheng, Detriana Kurzeja-Edwards, Stephen P. Diggle
Summary: Chronic, highly antibiotic-resistant infections in cystic fibrosis lungs contribute to increasing morbidity and mortality. Pseudomonas aeruginosa, a common CF pathogen, exhibits resistance to multiple antibiotics, contributing to antimicrobial resistance. This study found that the diversity of P. aeruginosa variants within CF lung infections leads to varying susceptibility to R-pyocins, and suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Madeline Mei, Jacob Thomas, Stephen P. Diggle
Summary: The research revealed that heterogeneous populations of Pseudomonas aeruginosa exhibit varying susceptibility to R-pyocins, likely due to differences in the LPS core. Further studies suggest that there is heterogeneity in response to other types of LPS-binding antimicrobials as well.
Article
Immunology
Andrew Tony-Odigie, Leonie Wilke, Sebastien Boutin, Alexander H. Dalpke, Buqing Yi
Summary: Chronic Pseudomonas aeruginosa infections in cystic fibrosis (CF) patients are associated with the progression of lung disease. Recent studies suggest that certain commensal bacteria may protect the host from inflammation, with Streptococcus mitis showing potential in reducing inflammatory responses induced by P. aeruginosa infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
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
Respiratory System
Isabelle Fleurot, Raquel Lopez-Galvez, Pascal Barbry, Antoine Guillon, Mustapha Si-Tahar, Andrea Bahr, Nikolai Klymiuk, Jean-Claude Sirard, Ignacio Caballero
Summary: This study reveals a defective TLR5 signaling in the airway epithelium of cystic fibrosis (CF) patients, leading to excessive lung inflammation. These findings contribute to a better understanding of the pathogenesis of CF disease and provide potential therapeutic targets.
JOURNAL OF CYSTIC FIBROSIS
(2022)
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)
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)
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)
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
Nutrition & Dietetics
Aleksandra John, Joanna Gozdzik-Spychalska, Magdalena Durda-Masny, Wojciech Czainski, Natalia Pawlowska, Jolanta Wlizlo, Halina Batura-Gabryel, Anita Szwed
Summary: The study described the relationship between the prevalence of Pseudomonas aeruginosa (PA) and lung function, nutritional status, and gene mutation type in adult patients with cystic fibrosis (CF). The presence of PA was associated with lower FEV1% and BMI values. Severe gene mutation, undernutrition, and deterioration of lung function were linked to a higher probability of PA acquisition and resistance to antibiotic treatment.
Review
Medicine, Research & Experimental
Roberto Rosales-Reyes, Silvia Yalid Vargas-Roldan, Jose Luis Lezana-Fernandez, Jose Ignacio Santos-Preciado
Summary: Cystic fibrosis is a genetic disease that affects the respiratory and digestive systems, causing chronic lung infections and breathing difficulties. Mutations in the CFTR gene lead to imbalanced intracellular water content, resulting in sticky mucus and bacterial infections that ultimately affect lung function.
ARCHIVES OF MEDICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Tim Gerster, Michelle Wroebel, Casey E. Hofstaedter, Dominik Schwudke, Robert K. Ernst, Stefanie Ranf, Nicolas Gisch
Summary: Pseudomonas pathogens modify their lipid A during host entry to evade immune responses and adapt to different environments. This study characterizes the lipid A modifications in Pseudomonas syringae pv. phaseolicola (Pph) 1448A and identifies the conserved functions of PagL, LpxO, and EptA in lipid A modification. The findings provide useful mutant strains for further functional studies on lipid A modifications in Pph 1448A.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
J. Stuart Elborn, Francesco Blasi, Charles S. Haworth, Manfred Ballmann, Harm A. W. M. Tiddens, Marlene Murris-Espin, James D. Chalmers, Andre M. Cantin
Summary: Inhaled tobramycin therapy has shown effectiveness in reducing P. aeruginosa microbial density in sputum of bronchiectasis patients, leading to potential clinical benefits such as reduced hospitalizations, exacerbations, and symptoms. Definitive phase 3 trials are needed to determine the clinical efficacy and long-term safety of inhaled tobramycin in bronchiectasis patients with chronic P. aeruginosa infection.
RESPIRATORY MEDICINE
(2022)
Article
Microbiology
Richard D. Smith, Christi L. McElheny, Jerilyn R. Izac, Francesca M. Gardner, Courtney E. Chandler, David R. Goodlett, Yohei Doi, J. Kristie Johnson, Robert K. Ernst
Summary: In this study, a novel method for identifying colistin resistance in Enterobacter species and Klebsiella aerogenes is developed using MALDI-TOF MS. This method allows for rapid and accurate detection of resistance without the need for antimicrobial susceptibility testing. The study demonstrates that the MS assay is highly correlated with killing efficacy and can effectively predict how colistin would treat an infection. The use of MALDI-TOF MS for early identification of antimicrobial resistance can improve antimicrobial stewardship and patient outcomes.
MICROBIOLOGY SPECTRUM
(2022)
Article
Cell Biology
Debbie O'Reilly, Tim Downing, Sana Kouba, Marie Potier-Cartereau, Declan J. McKenna, Christophe Vandier, Paul J. Buchanan
Summary: Research has found that the voltage gated calcium channel CaV1.3 is increased in prostate cancer patients undergoing androgen deprivation therapy (ADT). Increased CaV1.3 isoforms promote resistance to ADT by upregulating store operated calcium entry (SOCE) and enhancing the proliferation and survival of castrate resistant prostate cancer cells.
Article
Microbiology
Andrew S. Bray, Richard D. Smith, Andrew W. Hudson, Giovanna E. Hernandez, Taylor M. Young, Hannah E. George, Robert K. Ernst, M. Ammar Zafar
Summary: This study investigates the biological cost of colistin resistance in Klebsiella pneumoniae. It finds that while colistin resistance reduces the ability of the bacteria to colonize the gut, it enhances their survival outside the host and therefore increases their transmission between hosts.
Article
Immunology
Erin M. Harberts, Daniel Grubaugh, Daniel C. Akuma, Sunny Shin, Robert K. Ernst, Igor E. Brodsky
Summary: This study investigates the activation mechanisms of lipid A in TLR4 and Casp11, finding that the location of specific secondary acyl chains determines the differential recognition of lipid A. This provides new insights into the activation mechanisms of TLR4 and Casp11 and highlights the importance of lipid A structure.
INFECTION AND IMMUNITY
(2022)
Article
Microbiology
Ad C. Fluit, Jumamurat R. Bayjanov, Barry J. Benaissa-Trouw, Malbert R. C. Rogers, Maria Diez-Aguilar, Rafael Canton, Michael M. Tunney, J. Stuart Elborn, Miquel B. Ekkelenkamp
Summary: The study analyzed genetic diversity and antibiotic susceptibility of H. influenzae strains from CF patients, finding limited resistance levels with the highest against co-trimoxazole. Sequences encoding a carbamate kinase and haemoglobin-related proteins may contribute to colonization in the CF lung. Identified virulence factors were not deemed necessary for colonization.
JOURNAL OF MEDICAL MICROBIOLOGY
(2022)
Article
Immunology
Debaki R. Howlader, Sayan Das, Ti Lu, Rahul Shubhra Mandal, Gang Hu, David J. Varisco, Zackary K. Dietz, Siva Sai Kumar Ratnakaram, Robert K. Ernst, William D. Picking, Wendy L. Picking
Summary: We formulated a candidate subunit vaccine against Pseudomonas aeruginosa (Pa), which activates genes from multiple immunological pathways and elicits a protective Th1-Th17 response. Immunized mice showed an adaptive response after infection, while PBS-vaccinated mice experienced rapid onset of an inflammatory response.
Article
Microbiology
Alison J. Scott, Alexis A. Smith, Ron M. A. Heeren, Utpal Pal, Robert K. Ernst
Summary: Spatially aware de novo discovery methods play a crucial role in identifying therapeutic targets in complex interphylum interactions. This study evaluated the potential of matrix-assisted desorption/ionization mass spectrometry imaging (MALDI-MSI) as a spatial omics method to simultaneously profile an arthropod vector and a mammalian skin in a bite model. The results demonstrated the feasibility of using MSI to analyze lipids and observe lipid reorganization at the bite site in both the tick and mammalian skin.
Article
Microbiology
Courtney E. Chandler, Casey E. Hofstaedter, Tracy H. Hazen, David A. Rasko, Robert K. Ernst
Summary: Individuals with cystic fibrosis often suffer from recurrent infections, and Pseudomonas aeruginosa is a common bacterium found in their airways. This study examined early isolates of P. aeruginosa from young CF patients to understand the genetic adaptations during colonization and infection. The study found that specific phenotypic adaptations did not have a clear genetic basis, and the geography of patient origin did not significantly influence genetic adaptation. Overall, the study adds to the understanding of P. aeruginosa evolution in CF airway disease.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Gang Hu, David J. Varisco, Sayan Das, C. Russell Middaugh, Francesca Gardner, Robert K. Ernst, Wendy L. Picking, William D. Picking
Summary: Toll-like receptor (TLR) agonists are potential immune-enhancing adjuvants included in licensed vaccines. BECC438 and BECC470, novel TLR4 agonists, have shown effective adjuvant potential against viral and bacterial diseases. This study provides detailed characterization and formulation potential for these chemically defined TLR4 agonists.
Article
Microbiology
Richard D. Smith, Min Zhan, Shanshan Zhang, Surbhi Leekha, Anthony Harris, Yohei Doi, Scott Evans, J. Kristie Johnson, Robert K. Ernst
Summary: This study evaluated a new rapid lipid analysis technique called FLAT MS for direct identification of pathogens from blood cultures. FLAT MS showed slight differences in accuracy compared to other FDA-approved methods for identifying Gram-positive bacteria, Gram-negative bacteria, and yeast. The time-to-results and hands-on time of FLAT MS were comparable to other methods.
JOURNAL OF CLINICAL MICROBIOLOGY
(2023)
Article
Materials Science, Biomaterials
John Redmond, Helen O. McCarthy, Paul Buchanan, Tanya J. Levingstone, Nicholas J. Dunne
Summary: 2D culture lacks proper cell-cell and cell-matrix interactions, resulting in exaggerated responses to therapeutic agents. 3D models, such as the collagen-based scaffold developed in this study, offer a more accurate representation of in vivo cancers and have the potential to explore gene expression profiles and assess the efficacy of therapeutic agents in treating breast cancer.
BIOMATERIALS ADVANCES
(2022)
Review
Oncology
Alex J. Eustace, Min Jie Lee, Grace Colley, Jack Roban, Tim Downing, Paul J. Buchanan
Summary: TNBC is an aggressive form of breast cancer with a lack of targeted therapies, making chemotherapy a key treatment option with limited efficacy due to acquired resistance. Changes in calcium signalling play a key role in promoting disease progression and therapy resistance in TNBC, presenting important research opportunities.
CANCER DRUG RESISTANCE
(2022)
Article
Biochemistry & Molecular Biology
Debbie O'Reilly, Paul J. Buchanan
Summary: This study reveals that CaV1.3 can modulate hypoxic signaling and impact on prostate cancer tumor biology. ADT upregulates CaV1.3 expression and promotes the generation of signals such as HIF-1α through the upregulation of SOCE. Under hypoxic conditions, inhibition of CaV1.3 in hypoxic-sensitive cells significantly reduces HIF-1α expression, while it increases HIF-1α expression in CRPC cells.