Article
Infectious Diseases
Chani Rakov, Shira Ben Porat, Sivan Alkalay-Oren, Ortal Yerushalmy, Mohanad Abdalrhman, Niv Gronovich, Lina Huang, David Pride, Shunit Coppenhagen-Glazer, Ran Nir-Paz, Ronen Hazan
Summary: Providencia spp. are emerging pathogens mainly in nosocomial infections, with Providencia stuartii playing a significant role in urinary tract infections and biofilm formation in catheterized patients. Multiple drug resistant P. stuartii is associated with hospital outbreaks, leading to difficult treatments. Phage therapy shows promise in combating antibiotic-resistant infections, but the limited availability of phages targeting Providencia spp. restricts its use. The isolation and characterization of bacteriophages from sewage samples, targeting clinical Providencia spp. strains, demonstrates potential for treatment of antibiotic-resistant infections, including urinary tract infections.
Article
Infectious Diseases
Valerio Capitani, Gabriele Arcari, Alessandra Oliva, Federica Sacco, Gaia Menichincheri, Linda Fenske, Riccardo Polani, Giammarco Raponi, Guido Antonelli, Alessandra Carattoli
Summary: This article reports a four-patient outbreak caused by Providencia stuartii in a hospital in Rome. Phenotypic analysis and whole-genome sequencing revealed highly related strains with XDR characteristics. The strains carried various virulence factors and resistance genes, which were found on plasmids similar to those found in previous Klebsiella pneumoniae strains in the same hospital. The emergence of XDR P. stuartii strains poses a significant public health threat, and monitoring their spread and developing new control and treatment strategies is crucial.
Article
Immunology
Swati Sharma, Sangita Pramanik, Pooja Marndi, Tuhina Banerjee
Summary: This study reveals CRPS as an important cause of healthcare associated infections, which is often overlooked due to the burden of carbapenem resistance in other bacteria.
INDIAN JOURNAL OF MEDICAL RESEARCH
(2023)
Article
Microbiology
Mengdi Gao, Chunlin Feng, Yongan Ji, Yaokai Shi, Weina Shi, Lei Zhang, Shuang Liu, Anqi Li, Xueya Zhang, Qiaoling Li, Junwan Lu, Qiyu Bao, Hailin Zhang
Summary: In this study, a novel chromosome-encoded aminoglycoside nucleotidyltransferase (ANT), AadA36, was identified from the Providencia stuartii strain P14 isolated from a burn patient at a hospital in Wenzhou, China. The AadA36 gene conferred resistance to spectinomycin and streptomycin, and its identification enhances our understanding of resistance mechanisms and gene dissemination in microbial populations.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Michael Biggel, Sophia Johler, Tim Roloff, Sarah Tschudin-Sutter, Stefano Bassetti, Martin Siegemund, Adrian Egli, Roger Stephan, Helena M. B. Seth-Smith
Summary: This study developed a bioinformatic tool called PorinPredict to predict defects in the outer membrane porin OprD of Pseudomonas aeruginosa, which are strongly associated with reduced carbapenem susceptibility. PorinPredict relies on a database of OprD variants and can identify inactivating mutations in the coding or promoter region. The tool was validated against P. aeruginosa genomes and showed a high correlation between OprD loss and meropenem nonsusceptibility, regardless of the presence of carbapenemases.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Joshua L. C. Wong, Sophia David, Julia Sanchez-Garrido, Jia Z. Woo, Wen Wen Low, Fabio Morecchiato, Tommaso Giani, Gian Maria Rossolini, Konstantinos Beis, Stephen J. Brett, Abigail Clements, David M. Aanensen, Silvi Rouskin, Gad Frankel
Summary: This study investigates the impact of mutations in OmpK36 on carbapenem resistance in Klebsiella pneumoniae. The researchers found that a recurrent 25c > t transition in ompK36 increases resistance by reducing the expression of OmpK36 in the outer membrane. This mutation attenuates the bacteria in a mouse pneumonia model but leads to treatment failure in the context of carbapenem therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
David R. Cameron, Melissa Pitton, Simone Oberhaensli, Katja Schlegel, Guy Prod'hom, Dominique S. Blanc, Stephan M. Jakob, Yok-Ai Que
Summary: This study aimed to genetically and phenotypically characterize Pseudomonas aeruginosa isolates collected during an outbreak of infection in a burn ICU. The results demonstrated the evolution of pathoadaptive genes and adaptive phenotypic traits in response to the burn environment. High-level carbapenem resistance evolved rapidly in parallel with increased antibiotic consumption during the outbreak.
MICROBIOLOGY SPECTRUM
(2022)
Article
Immunology
Saba Gul, Sajjad Ahmad, Asad Ullah, Saba Ismail, Muhammad Khurram, Muhammad Tahir ul Qamar, Abdulrahim R. Hakami, Ali G. Alkhathami, Faris Alrumaihi, Khaled S. Allemailem
Summary: In this study, a computational approach was used to design a multi-epitope vaccine against Providencia rettgeri. The predicted epitopes were evaluated and linked with an adjuvant to enhance the vaccine's efficacy. Docking studies and molecular dynamics simulations confirmed strong interactions between the designed vaccine and immune receptors, with exposed epitopes for recognition and processing by the host immune system.
Article
Microbiology
Vinicius C. N. de Moura, Deepshikha Verma, Isobel Everall, Karen P. Brown, Juan M. Belardinelli, Crystal Shanley, Megan Stapleton, Julian Parkhill, R. Andres Floto, Diane J. Ordway, Mary Jackson
Summary: The presence of Msp-type porins in MABSC infections is associated with virulence and resistance to biocides.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Ankita Khataniar, Abhichandan Das, Manash J. Baruah, Kusum K. Bania, Sanchaita Rajkhowa, Sami A. Al-Hussain, Magdi E. A. Zaki
Summary: This study investigates the bioactivity of C-2 quaternary indolinones against Providencia spp. and identifies moL12 as a compound with superior antimicrobial activity, showing promise for the development of novel treatments against urinary tract infections caused by Providencia spp. Computational studies support the pharmacokinetic properties of moL12, indicating its potential as a therapeutic agent.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Article
Multidisciplinary Sciences
Abera Abdeta, Adane Bitew, Surafel Fentaw, Estifanos Tsige, Dawit Assefa, Tadesse Lejisa, Yordanos Kefyalew, Eyasu Tigabu, Martin Evans
Summary: The study detected a high prevalence of multidrug-resistant and extremely drug-resistant carbapenemase-producing gram-negative bacteria, particularly among intensive care unit patients at healthcare facilities. This highlights the increasing difficulty in clinical management of infected patients and the need for last-resort antibiotics, potentially worsening the global antimicrobial resistance crisis. Robust antimicrobial resistance monitoring and infection prevention and control programs are necessary.
Article
Cell Biology
Xian-liang Zhao, Zhuang-gui Chen, Tian-ci Yang, Ming Jiang, Jie Wang, Zhi-xue Cheng, Man-jun Yang, Jia-xin Zhu, Tian-tuo Zhang, Hui Li, Bo Peng, Xuan-xian Peng
Summary: Exogenous glutamine can enhance the killing effect of antibiotics against multidrug-resistant bacteria, promote the influx of antibiotics, increase intracellular antibiotic concentrations, effectively prevent the development of antibiotic resistance, and provide new insights for the prevention or management of chronic, multidrug-resistant bacterial infections, bacterial persistence, and difficult-to-treat bacterial biofilms.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Microbiology
Richard A. Stanton, Davina Campbell, Gillian A. McAllister, Erin Breaker, Michelle Adamczyk, Jonathan B. Daniels, Joseph D. Lutgring, Maria Karlsson, Kyle Schutz, Jesse T. Jacob, Lucy E. Wilson, Elisabeth Vaeth, Linda Li, Ruth Lynfield, Paula M. Snippes Vagnone, Erin C. Phipps, Emily B. Hancock, Ghinwa Dumyati, Rebecca Tsay, P. Maureen Cassidy, Jacquelyn Mounsey, Julian E. Grass, Sandra N. Bulens, Maroya Spalding Walters, Alison Laufer Halpin
Summary: This study investigated carbapenem-resistant Pseudomonas aeruginosa (CRPA) in the United States through genetic sequencing and typing. The results revealed diverse sources of carbapenem resistance, including non-carbapenemase beta-lactamase genes. The study findings shed light on the genetic diversity and transmission mechanisms of carbapenem-resistant P. aeruginosa.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Zhuo Zhang, Lili Zhao, Manman Song, Jilong Luo, Hanghang Liu, Kun Xue, Chengshi Huang, Hongyan Chen, Junwei Ge
Summary: This study reported P. heimbachae strains causing post-weaning diarrhea and investigated their pathogenicity and biological characteristics. The strains showed resistance to antibiotics, invaded IPEC-J2 cells, and were capable of growing under low temperature. Additionally, they exhibited high pathogenicity in mice and piglets.
CURRENT MICROBIOLOGY
(2022)
Article
Microbiology
Wei Liu, Jia-Wei Tang, Jing-Wen Lyu, Jun-Jiao Wang, Ya-Cheng Pan, Xin-Yi Shi, Qing-Hua Liu, Xiao Zhang, Bing Gu, Liang Wang
Summary: This pilot study confirms the potentials of surface-enhanced Raman spectroscopy in fast and accurate discrimination of Klebsiella pneumoniae strains with different antibiotic resistance profiles through computational analysis.
MICROBIOLOGY SPECTRUM
(2022)
Article
Engineering, Biomedical
Robert Richter, Mohamed A. M. Kamal, Marcus Koch, Bart-Jan Niebuur, Anna-Lena Huber, Adriely Goes, Carsten Volz, Julia Vergalli, Tobias Kraus, Rolf Mueller, Nicole Schneider-Daum, Gregor Fuhrmann, Jean-Marie Pages, Claus-Michael Lehr
Summary: In this study, outer membrane vesicles (OMVs) from E. coli were utilized as a model to predict drug uptake across the complex cell envelope, showing a better correlation with reported bacterial accumulation data and the ability to discriminate high from low accumulating antibiotics. This approach offers a potential high throughput screening tool with high predictive capacity for identifying compound- and bacteria-specific passive uptake pathways in the future.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Chemistry, Physical
Karthika S. Nair, Neethu B. Raj, K. Madhavan Nampoothiri, Gayathri Mohanan, Silvia Acosta-Gutierrez, Harsha Bajaj
Summary: We successfully constructed giant vesicle models mimicking bacterial inner-membrane and outer-membrane using gel-assisted lipid swelling technique, and observed their membrane deformation behavior under osmotic stress. Inner-membrane vesicles composed of native bacterial lipids underwent small-scale remodeling, while outer-membrane vesicles assembled from lipopolysaccharide and bacterial lipids underwent global membrane deformation, generating complex curved structures.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Tanzir Ahmed, Jayesh Arun Bafna, Roland Hemmler, Karsten Gall, Richard Wagner, Mathias Winterhalter, Michael J. Vellekoop, Sander van den Driesche
Summary: This work presents a microsystem setup for sensitive biological membrane translocation measurements. Thin free-standing synthetic bilayer lipid membranes (BLM) are constructed in microfabricated silicon nitride apertures and used for electrophysiological measurements of pore proteins. The integration of pore-forming proteins is achieved through direct reconstitution or reconstitution via outer membrane vesicles (OMVs) released from Gram-negative bacteria. This microsystem allows for investigation of fast gating events, pore blocking, and gating events of small pores.
Article
Chemistry, Multidisciplinary
Jiajun Wang, Jigneshkumar Dahyabhai Prajapati, Fan Gao, Yi-Lun Ying, Ulrich Kleinekathoefer, Mathias Winterhalter, Yi-Tao Long
Summary: Chirality is important but often overlooked in biological and chemical processes due to technical limitations. Researchers have used an electrostatically asymmetric membrane channel to successfully identify chiral amino acids in single peptides. This study provides a new approach for developing chiral recognition and protein sequencing methods.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Smrithi R. Krishnan, Kalyanashis Jana, Amina H. Shaji, Karthika S. Nair, Anjali Devi Das, Devika Vikraman, Harsha Bajaj, Ulrich Kleinekathoefer, Kozhinjampara R. Mahendran
Summary: In this study, a transmembrane pore DpPorA was developed based on the natural pore PorACj using D-amino acid alpha-helical peptides. The DpPorA peptides were found to self-assemble into uniform cation-selective pores in lipid membranes and exhibited properties distinct from their L-amino acid counterparts. Molecular dynamics simulations further revealed the specific structure and conformation of the D-pores. These findings provide valuable insights for the design of complex pores for single-molecule sensing technologies.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Muriel Masi, Julia Vergalli, Ishan Ghai, Andrea Barba-Bon, Therese Schembri, Werner M. Nau, Daniel Lafitte, Mathias Winterhalter, Jean-Marie Pages
Summary: This study investigated the translocation and killing effects of different cephalosporins on Gram-negative bacteria. The results revealed that the activity and efficiency of the drugs were influenced by the expression of specific porins. Through experimentation and analysis, it was found that the net negative charge of one of the cephalosporins contributed to its higher permeation through less cation-selective porins. These findings provide insights into the susceptibility of specific bacteria strains to cephalosporins.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Igor V. Bodrenko, Tsedenia Alemu Zewdie, Jiajun Wang, Eshita Paul, Susanne Witt, Mathias Winterhalter
Summary: This study investigates protein-protein interaction using electrophysiology, focusing on the structure of the TolC-AcrA-AcrB complex and the inhibitory effect of potential efflux pump inhibitors. The findings suggest that the fluctuation of ion current and the average current through the TolC channel can be used as complementary measures to assess the interaction of the complex.
Review
Biochemistry & Molecular Biology
Jinane Tabcheh, Julia Vergalli, Anne Davin-Regli, Noha Ghanem, Jean-Marie Pages, Charbel Al-Bayssari, Jean Michel Brunel
Summary: Antibiotic resistance is increasing morbidity and mortality for non-curable infectious diseases. Novel strategies, such as effective antibiotic combinations and antibiotics with non-antibiotic activity-enhancing compounds, have emerged to combat multidrug-resistant microorganisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Abhishek Acharya, Ishan Ghai, Claudio Piselli, Jigneshkumar Dahyabhai Prajapati, Roland Benz, Mathias Winterhalter, Ulrich Kleinekathoefer
Summary: In this study, the molecular mechanism of an antibiotic permeating through a bacterial channel is revealed, with a focus on the role of conformational dynamics of the constriction loop. The dynamics of the L3 loop, specifically the F118 to S125 segment, at the constriction regions of the OmpF porin is investigated using temperature accelerated sliced sampling approach. The importance of hydrogen-bond stabilization in the conformational dynamics of the L3 loop is demonstrated through single channel electrophysiology experiments and applied-field simulations. The findings suggest that conformational dynamics of the constriction loop may play a general role in antibiotic permeation through porins.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Mrunal Patil, Krykun Serhii, Frederic Garzino, Quentin Gobert, Suzanne Giorgio, Jean-Manuel Raimundo, Jean-Michel Bolla, Michel Camplo
Summary: Antibiotic resistance has led to the need for new treatments against multidrug-resistant microorganisms. 5-fluorouracil (5-FU) has been proposed as an alternative due to its intrinsic antibacterial property, but its high toxicity at high doses raises concerns. This study synthesized 5-FU derivatives and assessed their efficacy against pathogenic bacteria, finding that compounds with tri-hexylphosphonium substitution on both nitrogen groups of 5-FU had significant activity against both Gram-positive and Gram-negative bacteria. Compound 6c, with an asymmetric linker group, had the highest antibacterial efficacy.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Multidisciplinary
Yao Chen, Andrea Barba-Bon, Bohumir Gruner, Mathias Winterhalter, M. Alphan Aksoyoglu, Sushil Pangeni, Maryam Ashjari, Klaudia Brix, Giulia Salluce, Yeray Folgar-Camean, Javier Montenegro, Werner M. Nau
Summary: Cobalt bisdicarbollides (COSANs) are used as selective and efficient molecular carriers to transport hydrophilic oligopeptides through membranes. They can permeate lipid bilayer membranes without causing membrane damage. COSANs transport arginine-rich and lysine-rich peptides effectively, but cannot transport small molecules or anionic cargos. The transportation mechanism is a molecular carrier mechanism, and living cell experiments show that a fluorescent peptide cargo can be delivered into the cytosol.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Samir Nandi, Karthika S. Nair, Harsha Bajaj
Summary: We constructed bacterial outer membrane-mimicking giant unilamellar vesicles (GUVs) with lipopolysaccharide (LPS) and investigated the arrangement of LPS in the vesicles. Furthermore, we studied the antimicrobial permeability activity of the vesicles using model peptides. Our findings provide insights into the mechanism of action of antimicrobial peptides in bacterial membranes, and demonstrate the capability of our model to quantify antimicrobial permeability.
Article
Biochemical Research Methods
Karthika S. Nair, Sreelakshmi Radhakrishnan, Harsha Bajaj
Summary: We achieve the dynamic assembly and disassembly of membrane-less compartments formed via liquid-liquid phase separation (LLPS) inside synthetic cells using complex coacervates as models. Semi-permeable giant unilamellar vesicles (GUVs) encapsulate biomolecules, including enzymes, required to regulate coacervates. Assembly and disassembly of coacervates are triggered by the diffusion of substrates through the membrane into the vesicle lumen. The coupling of enzyme networks in a single synthetic cell system enables reversible and out-of-equilibrium regulation of coacervates. GUVs with functional LLPS compartment assembly open up new avenues for constructing programmable autonomous synthetic cells with membrane-less organelles. The coacervate-in-vesicle platform has significant implications for understanding LLPS regulation mechanisms in cells.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Chemistry, Physical
Karthika S. Nair, Harsha Bajaj
Summary: Giant unilamellar vesicles (GUVs) are versatile and promising bio-membrane mimetic platforms used for various applications, including understanding membrane biophysical processes and constructing synthetic cells. This review discusses the advancements in GUV preparation techniques and the mechanisms behind their formation. The review also highlights the use of novel microfluidic-based techniques and different strategies for GUV immobilization. Additionally, the key applications of GUVs in studying membrane interface processes and constructing synthetic cells are described, along with a critical analysis of the pros and cons of different preparation technologies.
ADVANCES IN COLLOID AND INTERFACE SCIENCE
(2023)
Article
Chemistry, Physical
Stefan Milenkovic, Jiajun Wang, Silvia Acosta-Gutierrez, Mathias Winterhalter, Matteo Ceccarelli, Igor V. Bodrenko
Summary: Transmembrane beta-barrel proteins are versatile candidates for various technological applications and their behavior is influenced by environmental conditions. Comparing two highly homologous porins, OmpF and OmpC, we observed subtle amino acid substitutions that can modulate mass transport properties. These differences can be attributed to the disparities in the environmental conditions under which the porins are expressed. Our analysis not only highlights the advantages of enhanced sampling methods, but also provides valuable insights into the biological function and technical applications of these proteins.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
