Article
Chemistry, Multidisciplinary
Yosuke Nakata, Junhao Fu, Hiroaki Itoh, Suresh Panthee, Hiroshi Hamamoto, Kazuhisa Sekimizu, Masayuki Inoue
Summary: This study developed a method to synthesize five tryptophan isomers and applied them in solid-phase peptide synthesis. The substitution at position C3 was found to affect the structure and function of peptides and proteins. The synthesis of the five isomers was achieved through peptide elongation, resin-based macrocyclization, and global deprotection, and their reduced antibacterial activity highlighted the importance of the precise three-dimensional structure of tryptophan in lysocin E. This approach provides a new strategy for analyzing and modifying the specific functions of tryptophan-containing peptides and proteins.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Yanran Lu, Sandip Vibhute, Linsen Li, Antony Okumu, Steven C. Ratigan, Sheri Nolan, Jonathan L. Papa, Chelsea A. Mann, Anthony English, Anna Chen, Justin T. Seffernick, Bryan Koci, Leonard R. Duncan, Brieanna Roth, Jason E. Cummings, Richard A. Slayden, Steffen Lindert, Craig A. McElroy, Daniel J. Wozniak, Jack Yalowich, Mark J. Mitton-Fry
Summary: Novel bacterial topoisomerase inhibitors (NBTIs) are promising new antibiotics with lead compound 79 showing potent antibacterial activity, low resistance, favorable cardiovascular safety profile, and in vivo efficacy against methicillin-resistant Staphylococcus aureus.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Engineering, Environmental
Ana Yanez-Aulestia, Rosa-Maria Ramirez-Zamora
Summary: This study proposes an efficient strategy to enhance the performance of metallurgical copper slag for photodegradation applications. The addition of ascorbic acid promotes the Fe(III)/Fe(II) redox cycle on the slag's surface, producing Fe(II) species and preventing iron precipitation. Increasing the amount of ascorbic acid leads to higher salicylic acid degradation, H2O2 decomposition, and & BULL;OH production. The optimal CS0.100/AA0.100/H2O2 system shows significant degradation of levofloxacin and ciprofloxacin, with a higher degradation speed for levofloxacin. The reusability experiments demonstrate the chemical stability of the system, with antibiotics degradation staying above 90%.
JOURNAL OF ENVIRONMENTAL CHEMICAL ENGINEERING
(2023)
Article
Multidisciplinary Sciences
Htut Htut Htoo, Nhung Ngo Thi Tuyet, Kittiporn Nakprasit, Chanat Aonbangkhen, Vorrapon Chaikeeratisak, Warinthorn Chavasiri, Poochit Nonejuie
Summary: In an era where bacteria evolve resistance to antibiotics at a faster rate than new antibiotics are discovered, the search for new sources of antibacterial agents has become crucial. Plant-based natural products have gained interest as potential sources of antibacterial agents. Mansonone G, extracted from Mansonia gagei Drumm. heartwoods, has shown antibacterial activities against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli lptD4213, and its derivatives also exhibit similar antibacterial spectrum with improved activities.
Article
Agriculture, Multidisciplinary
Yan Wang, Shenting Zhou, Qian Liu, Seong-Hee Jeong, Liyan Zhu, Xiangming Yu, Xiaojian Zheng, Gongyuan Wei, Seon-Won Kim, Chonglong Wang
Summary: This study optimized an alpha-santalene synthetic operon in E. coli by manipulating ribosome binding sites (RBSs). Deletion of the tnaA gene led to an increase in alpha-santalene production. These results suggest that optimizing the RBS sets of the synthetic module and attenuating competitive pathways are promising approaches for improving terpenoid production.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Brock Brady, Wuwei Li, Nashwan Farooque, Christopher Ehrhardt, Mark E. Meyerho, Xuewei Wang
Summary: This article introduces a urinary catheter-based sensor for detecting the most common E. coli bacteria in urinary tract infections associated with the use of urinary catheters. By incorporating a nitrosating agent and indole into a silicone catheter, a red dimeric product called indoxyl red is generated, allowing for highly sensitive and specific color-based indole sensing. The method can be applied in real catheters to detect indole and E. coli in urine.
Article
Multidisciplinary Sciences
Ahmed R. Elbestawy, Hany F. Ellakany, Hatem S. Abd El-Hamid, Madiha S. Ibrahim, Ahmed R. Gado, Nagwa S. Mustafa, Ihab M. Moussa, Khalid S. Al-Maary, Dalia S. Al-Sarar, Hanan O. Alshammari, Turki M. Dawoud, Hassan A. Hemeg, Hussein M. Galal
Summary: This study evaluated the cross-protection ability of live attenuated E. coli vaccine against heterologous APEC serotypes, showing significant protection but subtle differences in clinical signs, post-mortem lesions, mortality rates, E. coli re-isolation, histopathological examination, final body weight, and feed conversion ratio.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2021)
Article
Immunology
Hossein Samiei, Shahram Nazarian, Abass Hajizade, Emad Kordbacheh
Summary: In this study, a chimeric protein comprising two antigens of Escherichia coli O157:H7 was designed and evaluated as a vaccine candidate using in silico techniques. The results showed that the proposed antigen has high antigenicity and conformation suitable for being a potent vaccine candidate. Immunization evaluation demonstrated that the protein is able to stimulate the immune responses of mice and provide protective immunity against E. coli O157:H7.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Sakuntala Mutyala, Shuwei Li, Himanshu Khandelwal, Da Seul Kong, Jung Rae Kim
Summary: This study found that acetate can be converted to succinate under microaerobic conditions by overexpressing citrate synthase (gltA) in Pseudomonas putida. The gltA-KT strain showed a nearly 50% improvement in succinate production compared to the wild type. Under optimal pH of 7.5, the accumulation of succinate was approximately 400% higher than that of the wild type. Overall, gltA overexpression alone resulted in 9.5% of the maximum theoretical yield in a minimal medium with acetate as the sole carbon source. This highlights the importance of citrate synthase in acetate conversion to succinate by P. putida under microaerobic conditions.
Article
Chemistry, Medicinal
Alexandre Borrel, Christian Melander, Denis Fourches
Summary: The study investigated the structure-activity relationships of fluoroquinolone analogues against multiple pathogens and developed predictive models using machine learning techniques. The results revealed consistent antibacterial potency of fluoroquinolones against different pathogens and unique patterns of strain selectivity and potency for certain analogues, suggesting their potential in designing new compounds with enhanced potency and selectivity.
MOLECULAR INFORMATICS
(2021)
Article
Multidisciplinary Sciences
Benjamin Russell Lewis, Muhammad R. R. Uddin, Mohammad Moniruzzaman, Katie M. M. Kuo, Anna J. J. Higgins, Laila M. N. Shah, Frank Sobott, Jerry M. M. Parks, Dietmar Hammerschmid, James C. C. Gumbart, Helen I. I. Zgurskaya, Eamonn Reading
Summary: Membrane efflux pumps are important in bacterial multidrug resistance. The authors here provide insights into the mechanism of inhibition against the periplasmic adaptor protein AcrA. The results suggest that an inhibitor can stabilize AcrA and hinder its signal transmission, which could be valuable for antimicrobial therapeutics development.
NATURE COMMUNICATIONS
(2023)
Article
Environmental Sciences
Michael Biggel, Sarah Hoehn, Andrea Frei, Kira Dassler, Christoph Jans, Roger Stephan
Summary: The study reveals the spread of E. coli ST131 lineage through wastewater and surface water, posing a significant challenge to public health and water management.
ENVIRONMENTAL POLLUTION
(2023)
Article
Biotechnology & Applied Microbiology
Linglong Fu, Mengning Sun, Weizhang Wen, Na Dong, Defa Li
Summary: This study describes an efficient and simple method for extracellular production of Ulp1 tool enzyme using a leaky E. coli strain. It was found that the addition of glycine increased the extracellular production of Ulp1 approximately four fold. The extracellular Ulp1 had high activities for cleaving SUMO fusion proteins and the cleaved peptide pBD2 exhibited antimicrobial activity. This method of extracellular production of tool enzymes is cost-effective and has potential applications in pharmaceutical, industrial, and biotechnological fields.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nishal M. Egodawaththa, Amy L. Knight, Jingxuan Ma, D. Andrew Knight, Eric Guisbert, Nasri Nesnas
Summary: Silver nanoparticles conjugated with organic ligands have been successfully synthesized and demonstrated significant antimicrobial activity and antibacterial capabilities against E. coli. The synthesis of functionalized silver nanoparticles is critical for the further development of silver-nanoconjugated antibacterial agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Hiroshi Hamamoto, Suresh Panthee, Atmika Paudel, Kenichi Ishii, Jyunichiro Yasukawa, Jie Su, Atsushi Miyashita, Hiroaki Itoh, Kotaro Tokumoto, Masayuki Inoue, Kazuhisa Sekimizu
Summary: Lysocin E, a lipopeptide with antibiotic activity against methicillin-resistant Staphylococcus aureus, shows enhanced antimicrobial activity through interactions with host serum proteins and microbial components.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Roxanna Hajbabaie, Matthew T. Harper, Taufiq Rahman
Summary: This study utilized molecular docking and analogue search based on GRL-0617 to identify promising novel scaffolds with potential as more potent PLpro inhibitors while reducing off-target interactions. The research followed a four-step approach, offering new insights and directions for SARS coronavirus studies.
Article
Infectious Diseases
Geng Zou, Marta Matuszewska, Fenglan Bai, Suya Wang, Shuang Wang, Huaixia Li, Yan Ke, Cheng Tang, Jinquan Li, Junni Tang, Rui Zhou
Summary: This study investigated the transmission and origination of MRSA in yak herds with limited antimicrobial use. MRSA isolates from the yaks were found to belong to the lineage that might originate from the prevalent community-acquired MRSA ST59 in China, highlighting the role of animals in the expansion of MRSA.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Christopher Heng Xuan Ha, Nung Kion Lee, Taufiq Rahman, Siaw San Hwang, Wai Keat Yam, Xavier Wezen Chee
Summary: This study demonstrates the use of regression QSAR modeling to predict the activity of INSTIs and applies the models to drug repositioning. The top-ranked compounds are further evaluated for their target engagement activity using molecular docking and accelerated Molecular Dynamics simulation, and their potential as INSTIs is assessed through literature search.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Geng Zou, Marta Matuszewska, Ming Jia, Jianwei Zhou, Xiaoliang Ba, Juan Duan, Caishi Zhang, Jian Zhao, Meng Tao, Jingyan Fan, Xiangming Zhang, Wenping Jin, Tianpen Cui, Xianyu Zeng, Min Jia, Xiaojuan Qian, Chao Huang, Wenxiao Zhuo, Zhiming Yao, Lijun Zhang, Shaowen Li, Lu Li, Qi Huang, Bin Wu, Huanchun Chen, Alexander W. Tucker, Andrew J. Grant, Mark A. Holmes, Rui Zhou
Summary: The study investigated the contribution of MRSA from Chinese pig farms to human infection. It found high levels of MRSA in Chinese pig farms, but no evidence of transmission to the human population. MRSA isolates from hospitals in China appear to be part of a widely distributed lineage.
Article
Biochemistry & Molecular Biology
Yasin Gokce, Orhan Erkan, Kamil Savas, Taufiq Rahman, Nazmi Yaras
Summary: This study investigated the role of store-operated calcium entry (SOCE) in calcium handling in diabetic rat cardiomyocytes and found that SOCE function was reduced while Orai1 and Orai3 protein expression was upregulated in diabetes. Losartan treatment did not affect the protein expression pattern. The imbalance between SOCE function and protein expression levels may be due to impaired interaction between Stim and Orai proteins.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Sandip Patel, Yu Yuan, Gihan S. Gunaratne, Taufiq Rahman, Jonathan S. Marchant
Summary: Two-pore channels (TPCs) are ancient members of the voltage-gated ion channel superfamily that are primarily found on acidic organelles. TPCs can be activated by ligands and have calcium and sodium permeability, with the ability to switch their ion selectivity in response to specific agonists.
Article
Chemistry, Medicinal
Xavier Chee Wezen, Aneesh Chandran, Rohan Sakariah Eapen, Elaine Waters, Laura Bricio-Moreno, Tommaso Tosi, Stephen Dolan, Charlotte Millership, Aras Kadioglu, Angelika Grundling, Laura S. Itzhaki, Martin Welch, Taufiq Rahman
Summary: This study used molecular docking and molecular dynamics simulations to model the binding mode of compound 1771 to LtaS. The model was validated and lead optimization resulted in an improved compound 4 with enhanced affinity for LtaS. Compound 4 reduced LTA production, induced aberrant morphology, and decreased bacteria titers in mice infected with S. aureus. Analysis of simulation trajectories revealed a possible transient cryptic pocket, and virtual screening led to the discovery of new inhibitors that potentiate beta-lactams against methicillin-resistant S. aureus.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Cell Biology
Luc R. A. Francis, Sarah L. Millington-Burgess, Taufiq Rahman, Matthew T. Harper
Summary: Thrombin activates platelets through PAR1 and PAR4, with PAR1 being the more rapidly activated receptor. Q94, an allosteric modulator of PAR1, has been reported to inhibit PAR1-G alpha q coupling in various cell lines, but its effects on human platelet activation have not been studied. Our data suggest that Q94 may have off-target effects in platelets independent of PAR1, precluding its use as a selective PAR1 allosteric modulator.
Editorial Material
Cell Biology
Taufiq Rahman, Sandip Patel
Summary: TRPML1 is an endolysosomally-expressed cation channel, activated by PI(3,5)P-2 and synthetic agonists like rapamycin. New high resolution cryo-EM structures of TRPML1 bound to both PI(3,5)P-2 and temsirolimus reveal molecular insights into how the channel integrates two agonists at distal sites but cooperatively.
Article
Biochemistry & Molecular Biology
Juliyan Gunasinghe, Siaw San Hwang, Wai Keat Yam, Taufiq Rahman, Xavier Chee Wezen
Summary: In this study, a QSAR model was developed to predict potential inhibitors for the high-risk human papillomavirus E1 protein, and the Drugbank database was screened using the model. Three compounds were identified as candidate scaffolds for the future design of E1 inhibitors based on molecular docking and dynamics simulations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Cell Biology
Alaa Droubi, Connor Wallis, Karen E. Anderson, Saifur Rahman, Aloka de Sa, Taufiq Rahman, Len R. Stephens, Philip T. Hawkins, Martin Lowe
Summary: This study identifies the inositol 5-phosphatase INPP5B as a key regulator of actin remodeling, BCR clustering, and downstream signaling in antigen-stimulated B cells. INPP5B acts by dephosphorylating PI(4,5)P-2, which is necessary for actin disassembly, BCR mobilization, and cell spreading. INPP5B may represent a potential target for the treatment of B cell malignancies caused by aberrant BCR signaling.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yu Yuan, Dawid Jaslan, Taufiq Rahman, Stephen R. Bolsover, Vikas Arige, Larry E. Wagner, Carla Abrahamian, Rachel Tang, Marco Keller, Jonas Hartmann, Anna S. Rosato, Eva-Maria Weiden, Franz Bracher, David Yule, Christian Grimm, Sandip Patel
Summary: This study reveals that TPC2 can selectively increase its permeability to calcium ions when co-activated by the endogenous ligands NAADP and PI(3,5)P-2. This finding indicates that the flux of different ions through the same channel can be independently controlled and identifies TPC2 as a potential coincidence detector that optimizes lysosomal calcium signaling.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Marta Matuszewska, Gemma G. R. Murray, Xiaoliang Ba, Rhiannon Wood, Mark A. Holmes, Lucy A. Weinert, Daniel J. Wilson
Summary: The transmission of MRSA from livestock to humans results in a faster adaptation to the human host than the loss of antibiotic resistance. Additionally, the stable inheritance of resistance-associated MGEs suggests that the impact of reducing antibiotic and zinc oxide use in European farms on livestock-associated MRSA will be slow to occur.
Review
Cell Biology
Sandip Patel, Yu Yuan, Cheng-Chang Chen, Dawid Jaslan, Gihan Gunaratne, Christian Grimm, Taufiq Rahman, Jonathan S. Marchant
Summary: This review discusses the electrophysiology of two-pore channels TPC1 and TPC2, including their gating by Ca2+-mobilizing messenger NAADP and/or the lipid PI(3,5)P-2, regulation by H+, Ca2+, and Mg2+, and impact of single-nucleotide polymorphisms. The article also explores the effect of various substances on channel activity, as well as the rerouting of channels to the cell surface for easier recording.
Article
Microbiology
Marta Matuszewska, Alicja Dabrowska, Gemma G. R. Murray, Steve M. Kett, Andy J. A. Vick, Sofie C. Banister, Leonardo Pantoja Munoz, Peter Cunningham, John J. Welch, Mark A. Holmes, Lucy A. Weinert
Summary: Staphylococcus aureus is a commensal and pathogen that infects humans and animals. This study investigates if S. aureus in fish is due to spillover from humans or host specialization. Results show that S. aureus in farmed fish is acquired repeatedly from humans, and wild fish populations do not carry the bacteria. This highlights the importance of understanding S. aureus spillover in aquaculture for fish and human health.
MICROBIOLOGY SPECTRUM
(2023)