Article
Multidisciplinary Sciences
Chelsey M. VanDrisse, Rosalie Lipsh-Sokolik, Olga Khersonsky, Sarel J. Fleishman, Dianne K. Newman
Summary: This study demonstrates that by engineering the structure of PodA protein and combining it with tobramycin, the killing effect on P. aeruginosa can be enhanced, especially on biofilms that are resistant to conventional antibiotic treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Infectious Diseases
Karan Gandhi, Shiv Dhiman, Rajat Arora, Danzel Marie Ramirez, Danyel Ramirez, Gilbert Arthur, Frank Schweizer
Summary: Metal ions, including Fe3+, influence the binding of antibiotics and the uptake of antibiotics by bacteria. Amphiphilic tobramycins, a new class of antibiotic potentiators, synergize with various antibiotics against Gram-negative bacteria. In this study, iron-deferoxamine conjugates were prepared and tested for their antibacterial activity and synergistic effects with antibiotics. The conjugates showed strong synergistic effects with outer-membrane-impermeable antibiotics and selectively improved the susceptibility of multidrug-resistant bacteria to tetracyclines. However, the antibiotic potentiating effect was not influenced by the Fe3+ concentration.
Article
Biochemistry & Molecular Biology
Roberta Genova, Pablo Laborda, Trinidad Cuesta, Jose Luis Martinez, Fernando Sanz-Garcia
Summary: Understanding the consequences of drug resistance in bacterial physiology is crucial for exploiting its weaknesses. Collateral sensitivity, a potentially exploitable phenotype, may not be conserved among different isolates. Identifying robust and conserved collateral sensitivity patterns is important for translating this knowledge into clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Devin Sindeldecker, Shaurya Prakash, Paul Stoodley
Summary: This study analyzed the zone of killing (ZOK) in Pseudomonas aeruginosa biofilms using both in vitro and in silico methods. The findings revealed that achieving a specific antibiotic concentration versus time constraint (AUC) could completely eradicate bacteria in the biofilms. This suggests that appropriate antibiotic concentrations and treatment duration may be effective against antibiotic-resistant and -tolerant biofilm infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Nuoyan Wang, Xuemin Chen, Jing Luo, Fei Deng, Fuguo Shi, Qin Wu, Yasi Huang, Qin Ouyang, Rongxin Qin, Hong Zhou
Summary: This study investigated the antibacterial sensitization effect of DHA27 combined with tobramycin in tobramycin-resistant Pseudomonas aeruginosa. The combination showed significant antibacterial effects on many resistant strains and reduced bacterial load in the spleen and lungs in a mouse model. The study also revealed that the effect was related to the inhibition of mRNA expression of aminoglycoside-modifying enzymes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Microbiology
So-Young Ham, Han-Shin Kim, Min Jee Jo, Jeong-Hoon Lee, Youngjoo Byun, Gang-Jee Ko, Hee-Deung Park
Summary: The combination of 6-gingerol analog and tobramycin showed stronger inhibitory effects on biofilm formation and virulence factor production compared to individual treatments in P. aeruginosa infections. This combined treatment reduced infectivity without inducing cytotoxic effects in human lung epithelial cells. The adjuvant effects of this combination may lead to improved therapeutic development in chronic infections.
MICROBIOLOGY SPECTRUM
(2021)
Article
Multidisciplinary Sciences
Silvia M. Caceres, Linda A. Sanders, Noel M. Rysavy, Katie R. Poch, Caroline R. Jones, Kyle Pickard, Tasha E. Fingerlin, Roland A. Marcus, Kenneth C. Malcolm, Jennifer L. Taylor-Cousar, David P. Nichols, Jerry A. Nick, Matthew Strand, Milene T. Saavedra
Summary: This study found that specific genes measured from peripheral blood leukocytes can predict clinical response to inhaled antibiotic therapy in patients with cystic fibrosis. Molecular quantification of systemic inflammation may indicate subgroups of CF patients with variations in underlying inflammation and with variable clinical responses to inhaled antibiotics.
Article
Respiratory System
Freddy Frost, Gregory R. Young, Laura Wright, Nahida Miah, Darren L. Smith, Craig Winstanley, Martin J. Walshaw, Joanne L. Fothergill, Dilip Nazareth
Summary: This study demonstrates that in adults with CF and P. aeruginosa infection, AZLI + IV performed better in improving lung function and quality of life compared to the current standard treatment.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Editorial Material
Immunology
Ana Paula Streling, Mohanad M. Al Obaidi, William D. Lainhart, Tirdad Zangeneh, Ayesha Khan, An Q. Dinh, Blake Hanson, Cesar A. Arias, William R. Miller
Summary: A study reported the emergence of non-susceptibility to cefiderocol in a subpopulation of Pseudomonas aeruginosa recovered from a patient without prior exposure to the antibiotic. Whole genome sequencing revealed mutations in major iron transport pathways linked to cefiderocol uptake, highlighting the importance of susceptibility testing before therapy with siderophore cephalosporins.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Melissa Pitton, Simone Oberhaensli, Fiona Appiah, Jean-Luc Pagani, Anne Fournier, Stephan M. Jakob, Yok-Ai Que, David R. Cameron
Summary: This study reports a case of small-colony variant (SCV) emergence of Pseudomonas aeruginosa in a patient undergoing aminoglycoside treatment for burn wound infection, and confirms the causative role of a single ispA mutation in SCV emergence and increased aminoglycoside resistance. The involvement of IspA in ubiquinone synthesis provides a possible link between electron transport and SCV formation in P. aeruginosa.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Abigail M. Rubio, Ellen G. Kline, Chelsea E. Jones, Liang Chen, Barry N. Kreiswirth, M. Hong Nguyen, Cornelius J. Clancy, Vaughn S. Cooper, Ghady Haidar, Daria Van Tyne, Ryan K. Shields
Summary: In this study, we compared the in vitro susceptibility of multidrug-resistant Pseudomonas aeruginosa isolates before and after exposure to ceftolozane-tazobactam and found treatment-emergent mutations in the AmpC gene, which were associated with altered resistance patterns. However, some ceftolozane-tazobactam-resistant isolates with AmpC mutations remained susceptible to imipenem-relebactam.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Instruments & Instrumentation
Delia Boffoli, Federica Bellato, Greta Avancini, Pratik Gurnani, Gokhan Yilmaz, Manuel Romero, Shaun Robertson, Francesca Moret, Federica Sandrelli, Paolo Caliceti, Stefano Salmaso, Miguel Camara, Giuseppe Mantovani, Francesca Mastrotto
Summary: Carbohydrate-based materials, particularly synthetic glycopolymers, are attractive for their low toxicity and immunogenicity, and can be used as multivalent ligands to target sugar-binding proteins. This study utilized RAFT polymerisation to synthesize novel diblock copolymers capable of complexing aminoglycoside antibiotic tobramycin for targeted drug delivery against Pseudomonas aeruginosa biofilms. The tobramycin-loaded complexes efficiently suppressed in vitro biofilm formation, highlighting their potential in combating nosocomial infections.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Bruna Bernar Dias, Fernando Carreno, Victoria Etges Helfer, Priscila Martini Bernardi Garzella, Daiane Maria Fonseca de Lima, Fabiano Barreto, Bibiana Verlindo de Araujo, Teresa Dalla Costa
Summary: This study aimed to investigate the impact of biofilm-forming P. aeruginosa infection on the penetration of tobramycin in the lung and epithelial lining fluid using microdialysis, and to develop a population pharmacokinetic model to evaluate the probability of therapeutic target attainment of current dosing regimens. The results showed that the recommended dosing regimens for acute and chronic infection achieved a high probability of target attainment in the lung for the most prevalent P. aeruginosa MIC.
Article
Biochemistry & Molecular Biology
Adeline Cezard, Delphine Fouquenet, Virginie Vasseur, Katy Jeannot, Fabien Launay, Mustapha Si-Tahar, Virginie Herve
Summary: By using scanning electron microscopy and fluorometry test, this study demonstrated that poly-L-lysine can enhance the bactericidal effects of commonly used antibiotics against drug-resistant Pseudomonas aeruginosa. The synergistic effects of the combination were confirmed in vitro and ex vivo, suggesting that pLK could be a potential adjuvant antibiotherapy against drug-resistant strains.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Gianmarco Mangiaterra, Nicholas Cedraro, Salvatore Vaiasicca, Barbara Citterio, Emanuela Frangipani, Francesca Biavasco, Carla Vignaroli
Summary: Persistent and viable but non-culturable (VBNC) Pseudomonas aeruginosa cells play a major role in the recurrence and non-responsiveness to antibiotics of cystic fibrosis (CF) lung infections. The entry into the VBNC state can be triggered by sub-inhibitory antibiotic concentrations found in the CF lung between therapeutic cycles. Two CF P. aeruginosa isolates were analyzed in this study, and the results suggest that drug efflux, specifically mediated by MexXY efflux pump overexpression, may play a crucial role in the abundance of VBNC cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Xuefei Zhong, Xia Wu, Devin K. Schweppe, Juan D. Chavez, Martin Mathay, Jimmy K. Eng, Andrew Keller, James E. Bruce
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2020)
Article
Oncology
Hong Peng, Sheng Pan, Yuanqing Yan, Randall E. Brand, Gloria M. Petersen, Suresh T. Chari, Lisa A. Lai, Jimmy K. Eng, Teresa A. Brentnall, Ru Chen
Review
Spectroscopy
Juan D. Chavez, Sung-Gun Park, Jared P. Mohr, James E. Bruce
Summary: This review discusses the development and challenges in studying the interactome using chemical cross-linking and high-performance mass spectrometry technologies. It highlights the application of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and its potential for improving the visualization of the interactome. Further developments in parallel MS array capabilities are also discussed.
MASS SPECTROMETRY REVIEWS
(2022)
Review
Biochemistry & Molecular Biology
Xiaoting Tang, Helisa H. Wippel, Juan D. Chavez, James E. Bruce
Summary: Protein structure is crucial for biological functions, and understanding it is fundamental in biological and biomedical research. Crosslinking mass spectrometry is an emerging technique that can capture transient information on protein interactions in their native environment. Combining XL-MS with traditional techniques has the potential to bridge the gap between structural biology and systems biology approaches.
Article
Medicine, Research & Experimental
Matthew A. Walker, Juan Chavez, Outi Villet, Xiaoting Tang, Andrew Keller, James E. Bruce, Rong Tian
Summary: One hallmark of impaired myocardial energetics in failing hearts is the downregulation of the creatine kinase (CK) system. A study found an inverse relationship between the activity and acetylation of CK muscle form (CKM) in human and mouse failing hearts, where hyperacetylation disrupted MM homodimer formation and reduced enzymatic activity. Deacetylation by sirtuin 2 improved dimer formation and restored CKM activity from failing heart tissue, suggesting a novel mechanism for improving high-energy phosphoryl transfer in heart failure.
Article
Neurosciences
F. A. Concepcion, M. N. Khan, J-D Ju Wang, A. D. Wei, J. G. Ojemann, A. L. Ko, Y. Shi, J. K. Eng, J-M Ramirez, N. P. Poolos
Summary: Phosphorylation changes occur at individual HCN channel amino acid residues during epileptogenesis, leading to altered HCN1 channel phosphorylation in epilepsy. The novel phosphosite S791 may be of pathogenic importance in epilepsy.
Review
Chemistry, Multidisciplinary
Juan D. Chavez, Helisa H. Wippel, Xiaoting Tang, Andrew Keller, James E. Bruce
Summary: Biological systems heavily rely on proteins for various functional roles, and recent advancements in mass spectrometry, chemical labeling, and informatics capabilities have provided insights into the structures of proteins, complexes, and networks within cells. These approaches, which benefit from the molecular detection specificity of mass spectrometry and proteomics, offer systems-level information about conformational changes and protein interactions in response to perturbations.
Review
Biochemistry & Molecular Biology
Helisa H. Wippel, Juan D. Chavez, Xiaoting Tang, James E. Bruce
Summary: This article provides an overview of recent technological developments and applications of qXL-MS, including the design and synthesis of cross-linkers, development of new liquid chromatography-MS methodologies, and computational developments for data interpretation.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Immunology
Radika Soysa, Jonathan C. Bean, Xia Wu, Sarah Lampert, Sebastian Yuen, Ian N. Crispe
Summary: The study revealed that early-derived subsets of cardiac macrophages and Kupffer cells exhibit resilience in the face of acute stress by temporarily losing adaptation to local tissue-specific niches while reasserting their generic myeloid identity.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Lichen Jing, Xia Wu, Maxwell P. Krist, Tien-Ying Hsiang, Victoria L. Campbell, Christopher L. McClurkan, Sydney M. Favors, Lawrence A. Hemingway, Charmie Godornes, Denise Q. Tong, Stacy Selke, Angela C. LeClair, Chu-Woo Pyo, Daniel E. Geraghty, Kerry J. Laing, Anna Wald, Michael Gale, David M. Koelle
Summary: SARS-CoV-2 elicits a strong T cell response, with CD8 and CD4 T cells from convalescent individuals recognizing infected cells and inactivated whole viral antigen respectively. CD8 T cells exhibit low specificity, while CD4 T cells show higher breadth. Additionally, some CD4 T cell lines enriched using SARS-CoV-2 can cross-recognize seasonal coronavirus antigens.
Article
Biochemical Research Methods
Tara K. Bartolec, Joshua J. Hamey, Andrew Keller, Juan D. Chavez, James E. Bruce, Marc. R. Wilkins
Summary: This study investigates the function of histidine protein methyltransferase Hpm1p in yeast and confirms its association with diverse phenotypes, including sugar metabolism regulation, through techniques such as mass spectrometry analysis.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Chemistry, Analytical
Ian R. Smith, Jimmy K. Eng, Anthony S. Barente, Alexander Hogrebe, Ariadna Llovet, Ricard A. Rodriguez-Mias, Judit Villen
Summary: Stable-isotope labeling with amino acids in cell culture (SILAC)-based metabolic labeling is a widely used proteomics approach for quantitative comparisons. In this study, a new strategy was developed to coisolate and fragment SILAC peptide pairs for relative quantification. The modified database search engine and developed tool facilitated the analysis and quantification of SILAC peptide pairs. The coisolation approach improved the expectation scores and achieved more quantifications compared to traditional methods.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Attila Kertesz-Farkas, Frank Lawrence Nii Adoquaye Acquaye, Kishankumar Bhimani, Jimmy K. Eng, William E. Fondrie, Charles Grant, Michael R. Hoopmann, Andy Lin, Yang Y. Lu, Robert L. Moritz, Michael J. MacCoss, William Stafford Noble
Summary: The Crux tandem mass spectrometry data analysis toolkit is a collection of algorithms for analyzing bottom-up proteomics tandem mass spectrometry data. Although many publications have described the individual components of Crux, a comprehensive summary has not been published since 2014. The goal of this work is to provide a summary of Crux's functionality, focusing on developments since 2014. Recent developments include speed improvements to the Tide search engine, a new score function, two new confidence estimation procedures, and three new tools.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemical Research Methods
Eric W. Deutsch, Luis Mendoza, David D. Shteynberg, Michael R. Hoopmann, Zhi Sun, Jimmy K. Eng, Robert L. Moritz
Summary: The Trans-Proteomic Pipeline (TPP) mass spectrometry data analysis suite has undergone continuous development and refinement since the publication of its first tools, PeptideProphet and ProteinProphet, 20 years ago. The latest release offers a wide range of tools for spectrum processing, spectrum searching, search validation, abundance computation, protein inference, and more. These tools incorporate machine-learning modeling to maximize information extraction and establish robust statistical models for accurate information derivation. This article presents an overview of the latest TPP tools, their deployment on different platforms, tutorials for their usage, and synergistic projects leveraging TPP. The article concludes with outlined plans for future TPP development.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Helisa H. Wippel, Mariana Fioramonte, Juan D. Chavez, James E. Bruce
Summary: RNA-binding proteins (RBPs) interact with RNAs and other proteins to form ribonucleoprotein (RNP) complexes, which are involved in regulating various cellular processes. Heterogeneous nuclear ribonucleoproteins (hnRNPs) play a crucial role in transcription control and nuclear processing of transcripts, as well as in regulating alternative splicing of pre-mRNAs through spliceosome complex.