Article
Multidisciplinary Sciences
Calvin K. Lee, William C. Schmidt, Shanice S. Webster, Jonathan W. Chen, George A. O'Toole, Gerard C. L. Wong
Summary: This study reveals that changes in c-di-GMP levels in bacterial biofilms are not the sole factor determining surface commitment, as oscillations in c-di-GMP levels can propagate across generations. Additionally, the study demonstrates that modulation of c-di-GMP signals and cooperative surface commitment can be influenced by varying the interaction strength between PilO and SadC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Sherry L. Kuchma, George A. O'Toole
Summary: Surface sensing by Pseudomonas aeruginosa requires type IV pili (TFP), which play a critical role in the induction of the second messenger cAMP upon surface contact. Our study showed that TFP must be deployed and actively retracted by the PilT motor for the full induction of cAMP signaling. Furthermore, our data argue against one of the current models proposed to explain how TFP retraction triggers cAMP induction.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Multidisciplinary Sciences
Matthias D. Koch, Matthew E. Black, Endao Han, Joshua W. Shaevitz, Zemer Gitai
Summary: This study demonstrates that the human pathogen Pseudomonas aeruginosa actively senses surface stiffness using type IV pili (TFP). Stiffness sensing is shown to be nonlinear and plays an important role in the induction of virulence factor regulator within a specific physiological range. Traction force measurements and pilus retraction experiments reveal that TFP is capable of deforming stiff substrates. A quantitative biomechanical model is developed to explain the transcriptional response to stiffness, and it is validated by manipulating the ATPase activity of TFP motors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Kimberly A. Coggan, Matthew G. Higgs, Evan D. Brutinel, Jeremiah N. Marden, Peter J. Intile, Hanne C. Winther-Larsen, Michael Koomey, Timothy L. Yahr, Matthew C. Wolfgang
Summary: This study unveils two linked but independent regulatory systems governing Tfp biogenesis in Pseudomonas aeruginosa. We also demonstrate the importance of different phosphorylation states of the AlgZ/AlgR two-component system in Tfp biogenesis. Overall, this study furthers our understanding of the complex regulatory mechanisms that govern the production of a critical and multifaceted virulence factor.
Article
Multidisciplinary Sciences
Maria Victoria Pepe, Celeste Dea, Camila Genskowsky, Dario Capasso, Mara Sabrina Roset, Adriana Valeria Jager, Fernando Peruani, Arlinet Kierbel
Summary: The formation of long-lived bacterial clusters is crucial in the development of many bacterial diseases. This study reveals that Pseudomonas aeruginosa can form permanent bacterial clusters on polarized MDCK epithelium without requiring irreversible adhesion, cell proliferation, or a phenotypic transition. By combining experiments and a mathematical model, the researchers demonstrate that the formation process is mediated by type IV pili and that it involves a stochastic process of reversible attachment.
Article
Microbiology
C. J. Geiger, G. A. OToole
Summary: Biofilm formation in Pseudomonas aeruginosa involves an increase in intracellular cAMP, which is dependent on functional type IV pili (T4P) signaling through the Pil-Chp system. This study investigates the role of the T4P retraction motor PilT in surface sensing and cAMP production. The findings suggest that PilT interacts with PilJ to transmit the surface signal and increase cAMP production. These findings contribute to our understanding of T4P-dependent surface sensing in P. aeruginosa.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Microbiology
Xuerui Bao, Ellen Goeteyn, Aurelie Crabbe, Tom Coenye
Summary: D,L-malate enhances ciprofloxacin activity against P. aeruginosa, improving antibiotic therapy in infection environments. The choice of model system influences the outcome of the experiment, emphasizing the importance of using models that closely mimic the in vivo environment. This study confirms the potential of D,L-malate to enhance ciprofloxacin activity against P. aeruginosa-associated infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Mona Bove, Xuerui Bao, Andrea Sass, Aurelie Crabbe, Tom Coenye
Summary: The combination of QSI and tobramycin for eradicating Pseudomonas aeruginosa biofilms did not show evolution-proof characteristics, as bacterial resistance mutations were identified in genes involved in antibiotic resistance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Microbiology
Katherine J. Graham, Lori L. Burrows
Summary: This review focuses on recent microscopy innovations used to visualize T4P in live cells to reveal the dynamics of their retraction and extension. The proposed mechanisms by which T4P facilitate bacterial surface sensing are discussed, including the role of PilY1, two-component signal transduction pathways, force-induced structural modifications of the major pilin, and altered dynamics of the T4P motor complex.
JOURNAL OF BACTERIOLOGY
(2021)
Article
Chemistry, Physical
Jacobo Hernandez-Montelongo, Gianlucca G. Nicastro, Thays de O. Pereira, Mariana Zavarize, Marisa M. Beppu, Waldemar A. A. Macedo, Regina L. Baldini, Monica A. Cotta
Summary: Materials coated with nanofilms obtained by polyelectrolytes assembled layer-by-layer show promising antibacterial effects, with nanofilms of hyaluronan/chitosan (HA/CHI) exhibiting satisfactory effects against certain human pathogenic bacteria but less efficient against Pseudomonas aeruginosa. Understanding the interaction between P. aeruginosa and HA/CHI nanofilms involves evaluating the role of type IV pili (T4P) and lipopolysaccharide (LPS) structures in initial adhesion, with genetically modified strains revealing different adhesion behaviors. Although the HA/CHI nanofilm demonstrates antibacterial effects, the lack of LPS may partially protect bacteria from the nanofilm, affecting its efficiency over longer culture times.
SURFACES AND INTERFACES
(2021)
Article
Immunology
Sujatha Subramoni, Muhammad Zulfadhly Bin Mohammad Muzaki, Sean C. M. Booth, Staffan Kjelleberg, Scott A. Rice
Summary: The study utilized a mixed-species biofilm community, revealing that Pseudomonas aeruginosa, despite its low abundance, plays a critical role in the community's function, and that it affects interspecific interactions by modulating biofilm structure and physiology.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Amelia K. Schmidt, Alexa D. Fitzpatrick, Caleb M. Schwartzkopf, Dominick R. Faith, Laura K. Jennings, Alison Coluccio, Devin J. Hunt, Lia A. Michaels, Aviv Hargil, Qingquan Chen, Paul L. Bollyky, David W. Dorward, Jenny Wachter, Patricia A. Rosa, Karen L. Maxwell, Patrick R. Secor
Summary: The study reveals that the Pf phage protein PfsE inhibits the assembly of type IV pili, providing resistance to superinfection by phages that use type IV pili as a receptor. This finding has implications for the pathogenesis of P. aeruginosa.
Article
Microbiology
Amelia K. Schmidt, Alexa D. Fitzpatrick, Caleb M. Schwartzkopf, Dominick R. Faith, Laura K. Jennings, Alison Coluccio, Devin J. Hunt, Lia A. Michaels, Aviv Hargil, Qingquan Chen, Paul L. Bollyky, David W. Dorward, Jenny Wachter, Patricia A. Rosa, Karen L. Maxwell, Patrick R. Secor
Summary: Pseudomonas aeruginosa is often infected by Pf bacteriophages, which can lead to cell lysis during superinfection. The Pf protein PA0721, also known as PfsE, suppresses twitching motility in P. aeruginosa by binding to the T4P protein PilC, providing resistance to Pf infection and potentially modulating biofilm formation and virulence in the host bacteria.
Editorial Material
Biochemistry & Molecular Biology
Leonie Unterholzner
Summary: The DNA sensor cGAS and its adaptor STING form an ancient pathogen detection mechanism, but its conservation across the animal kingdom is uncertain. In this article in Cell, Kranzusch and colleagues identify numerous cGAS-like receptors and uncover networks of second messengers that activate innate immune responses in animals.
Editorial Material
Microbiology
Kara B. De Leon
Summary: Kara B. De Leon works in microbial ecology and her perspective on initial cell attachment to a surface in an environment was changed by the research paper authored by C. K. Lee et al.
Letter
Dermatology
Allison Kirchner, Vishnutheertha Kulkarni, Jeffrey Rajkumar, Ahmed Usman, Shahzeb Hassan, Ernest Y. Lee
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Critical Care Medicine
Joshua Keefe, Chen Yao, Shih-Jen Hwang, Paul Courchesne, Gha Young Lee, Josee Dupuis, Joseph P. Mizgerd, George O'Connor, George R. Washko, Michael H. Cho, Edwin K. Silverman, Daniel Levy
Summary: This study demonstrated a potential causal relationship between plasma soluble receptor for advanced glycation end-products (sRAGE) levels and lung function traits through integrated genomic analysis, providing insight into the therapeutic implications of targeting the AGER/sRAGE axis for inflammation-related lung diseases.
Letter
Dermatology
Allison Kirchner, Mit Patel, Vishnutheertha Kulkarni, Ahmed Usman, Ernest Y. Lee
INTERNATIONAL JOURNAL OF DERMATOLOGY
(2022)
Article
Chemistry, Physical
Huaqing Liu, Yiwu Zong, Mengjie Zu, Thomas G. Mason, Fangfu Ye, Kun Zhao
Summary: The study investigates the self-assembly of Brownian colloids on curved surfaces, demonstrating the significant influence of curvature on the phase behavior. Experimental findings reveal phase diagram changes with curvature, while simulations illustrate helical structures formed by square platelets packing on cylinders. These results highlight the control over particle self-assembly through curvature and depletion attraction-induced orientational confinement.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Wujing Xian, Matthew R. Hennefarth, Michelle W. Lee, Tran Do, Ernest Y. Lee, Anastassia N. Alexandrova, Gerard C. L. Wong
Summary: AMPs preferentially permeate prokaryotic membranes via electrostatic binding and membrane remodeling. High salt suppresses this action, but histidines in marine AMPs can interact with salt ions to neutralize phosphate charge and facilitate pore formation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biology
Jingchao Zhang, Huijun Wu, Di Wang, Lanxin Wang, Yifan Cui, Chenxi Zhang, Kun Zhao, Luyan Ma, Gerald Pier
Summary: Biofilm formation is a major cause of persistent infections. The intracellular glycosyl hydrolase PslG plays a crucial role in the synthesis of the exopolysaccharide PSL, which is essential for biofilm matrix formation in the opportunistic pathogen Pseudomonas aeruginosa. Lack of PslG or its hydrolytic activity enhances PSL signaling, affects cyclic-di-GMP levels during cell division, and alters the localization of PSL, resulting in the formation of long chains of bacterial cells and fast-forming biofilm microcolonies.
Article
Immunology
Kaitlyn Grando, Lauren K. Nicastro, Sarah A. Tursi, Jaime De Anda, Ernest Y. Lee, Gerard C. L. Wong, Cagla Tukel
Summary: Bacterial amyloid curli and Staphylococcus phenol-soluble modulins (PSMs) are implicated in the pathogenesis of autoimmune diseases by driving immune responses through complex formation with DNA. This study revealed that one of the Staphylococcus PSMs, PSM alpha 3, directly interacts with oligonucleotides to promote amyloid fibril formation and complex formation with bacterial DNA. Additionally, exposure to Staphylococcus biofilms induced autoimmune responses in a PSM-dependent manner.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Joshua A. Keefe, Xander H. T. Wehrens, Dobromir Dobrev
CARDIOVASCULAR RESEARCH
(2022)
Review
Toxicology
Joshua A. Keefe, Oliver M. Moore, Kevin S. Ho, Xander H. T. Wehrens
Summary: This review provides a comprehensive overview of the roles of Ca2+-handling proteins in healthy cardiac function and the mechanisms by which mutations in these proteins contribute to inherited arrhythmias. The major Ca2+ channels and Ca2+-sensitive regulatory proteins involved in cardiac excitation-contraction coupling are discussed, with special emphasis on the function of the RyR2 macromolecular complex. Inherited arrhythmia disorders caused by mutations in Ca2+-handling proteins are also discussed.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Joshua A. Keefe, Mohit M. Hulsurkar, Svetlana Reilly, Xander H. T. Wehrens
Summary: Atrial fibrillation is a common arrhythmia in adults, with its prevalence increasing with age. Current clinical management focuses on treating the symptoms rather than addressing the underlying molecular mechanisms. Animal models, particularly those exhibiting spontaneous atrial fibrillation without the need for supraphysiologic stimuli, can help uncover the underlying mechanisms of the condition.
Review
Cardiac & Cardiovascular Systems
Mary R. Sy, Joshua A. Keefe, Jeffrey P. Sutton, Xander H. T. Wehrens
Summary: Space medicine is crucial for human exploration of outer space and contributes to advancements in science, technology, and medicine. Astronauts and spaceflight participants face unique health challenges due to the harsh conditions in outer space, including microgravity and other hazards, particularly in relation to the heart. This review summarizes the existing literature on the effects of spaceflight on cardiac structure and function, as well as the impact of microgravity on cardiac calcium handling. The findings can inform future studies and therapies, and are also relevant to other physiological states resembling microgravity, such as prolonged horizontal bed rest and immobilization.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Hong Zhang, Wenchao Zhang, Yiwu Zong, Dongyang Kong, Kun Zhao
Summary: In this study, the effects of different factors on bacterial adhesion and evolution at the oil-water interface were investigated using Pseudomonas aeruginosa PAO1 as a model system. The results showed that PAO1 cells exhibited chemotactic behavior towards dodecane. The dynamics analysis revealed a transition from reversible to irreversible attachment of cells at the interface, accompanied by interface aging and the formation of a gel-like interface. Exopolysaccharides played an important role in this process. These findings provide insights into bacterial behavior at the oil-water interface and may lead to the development of strategies for controlling bacterial colonization.
Article
Chemistry, Multidisciplinary
Haleh Alimohamadi, Jaime de Anda, Michelle W. Lee, Nathan W. Schmidt, Taraknath Mandal, Gerard C. L. Wong
Summary: Peptide-induced transmembrane pore formation is common in biology, but directly observing the structure of these pores is difficult. Experimental determination of the structure and phase behavior of peptide-lipid systems, particularly the geometric parameters of cubic phases, is relatively straightforward. By leveraging the theory of anisotropic inclusions, researchers have developed a simple method to estimate the size of transmembrane pores and found that the estimates align well with known pore sizes. Antimicrobial peptides are able to induce stable pores, while cell-penetrating peptides form highly unstable pores.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Medicine, Research & Experimental
Jia Song, Jose Alberto Navarro-Garcia, Jiao Wu, Arnela Saljic, Issam Abu-Taha, Luge Li, Satadru K. Lahiri, Joshua A. Keefe, Yuriana Aguilar-Sanchez, Oliver M. Moore, Yue Yuan, Xiaolei Wang, Markus Kamler, William E. Mitch, Gema Ruiz-Hurtado, Zhaoyong Hu, Sandhya S. Thomas, Dobromir Dobrev, Xander H. T. Wehrens, Na Li
Summary: Chronic kidney disease (CKD) is associated with a higher risk of atrial fibrillation (AF). The mechanism linking CKD and AF is unclear. This study found that elevated NLRP3 inflammasome activity in atria of CKD patients contributed to the development of AF. Inhibiting NLRP3 or neutralizing IL-113 effectively reduced the occurrence of AF.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Calvin K. Lee, William C. Schmidt, Shanice S. Webster, Jonathan W. Chen, George A. O'Toole, Gerard C. L. Wong
Summary: This study reveals that changes in c-di-GMP levels in bacterial biofilms are not the sole factor determining surface commitment, as oscillations in c-di-GMP levels can propagate across generations. Additionally, the study demonstrates that modulation of c-di-GMP signals and cooperative surface commitment can be influenced by varying the interaction strength between PilO and SadC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)