Article
Chemistry, Medicinal
Liqiang Hu, Huixin Yang, Tao Yu, Fangfang Chen, Runqiu Liu, Shuyuan Xue, Shuangzhan Zhang, Wuyu Mao, Changge Ji, Hao Wang, Hexin Xie
Summary: This study demonstrates the effectiveness of stereochemically altered cephalosporins as potent inhibitors against NDM-1, a major cause of antibiotic resistance. The findings provide a new approach to combat antibiotic resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Vikram Khipple Mulligan, Sean Workman, Tianjun Sun, Stephen Rettie, Xinting Li, Liam J. Worrall, Timothy W. Craven, Dustin T. King, Parisa Hosseinzadeh, Andrew M. Watkins, P. Douglas Renfrew, Sharon Guffy, Jason W. Labonte, Rocco Moretti, Richard Bonneau, Natalie C. J. Strynadka, David Baker
Summary: This study presents a structure-guided computational method for designing peptide macrocycles using a mixture of L- and D-amino acids to inhibit therapeutic targets. The experimental results show that this method can effectively predict peptide binding propensity and inhibitory activity, as demonstrated in the interaction with NDM-1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Jacqueline Findlay, Laurent Poirel, Julie Kessler, Andreas Kronenberg, Patrice Nordmann
Summary: The study in Switzerland found that NDM-positive CPE, primarily consisting of Klebsiella pneumoniae and Escherichia coli, were prevalent, with NDM-1 and NDM-5 variants being the most common. Some isolates also co-produced a second carbapenemase and a 16S rRNA methylase. Successful plasmids and global lineages were identified as major factors contributing to the increasing prevalence of NDMs in Switzerland.
EMERGING INFECTIOUS DISEASES
(2021)
Article
Chemistry, Medicinal
Zainab Bibi, Irfa Asghar, Naeem Mahmood Ashraf, Iftikhar Zeb, Umer Rashid, Arslan Hamid, Maria Kanwal Ali, Ashraf Atef Hatamleh, Munirah Abdullah Al-Dosary, Raza Ahmad, Muhammad Ali
Summary: This study utilized virtual screening and molecular dynamics simulations to explore phytochemicals as inhibitors of New Delhi Metallo-beta-lactamase (NDM-1). Three potential inhibitors were identified based on their docking scores, RMSD values, and other critical parameters. These findings could contribute to addressing antibiotic resistance.
Article
Biochemistry & Molecular Biology
Han Gao, Jia-Qi Li, Peng-Wei Kang, Jia-Zhu Chigan, Huan Wang, Lu Liu, Yin-Sui Xu, Le Zhai, Ke-Wu Yang
Summary: This study constructed and characterized an effective M beta L inhibitor, which showed preferential inhibition against NDM-1, potential antibacterial activities, and synergistic effects with meropenem. The research provided a new framework for the development of NDM-1 inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Wen Bin Jin, Chen Xu, Xiao Lin Qi, Ping Zeng, Wei Gao, Ki Hon Lai, Jiachi Chiou, Edward W. C. Chan, Yun-Chung Leung, Tak Hang Chan, Kwok-Yin Wong, Sheng Chen, Kin-Fai Chan
Summary: Efficient construction of a series of trans-1,3,4-trisubstituted pyrrolidines via boric acid-catalyzed 1,3-dipolar cycloaddition for biological evaluation against NDM-1 positive carbapenem-resistant Enterobacteriaceae. Compound 10e showed low cytotoxicity, moderate NDM-1 enzyme inhibition, and potent synergistic activity against clinically isolated NDM-1 positive CRE, suggesting it as a promising starting point for carbapenem antibiotic adjuvants.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Alessandra Piccirilli, Emanuele Criscuolo, Fabrizia Brisdelli, Paola Sandra Mercuri, Sabrina Cherubini, Maria Laura De Sciscio, Mauro Maccarrone, Moreno Galleni, Gianfranco Amicosante, Mariagrazia Perilli
Summary: Study on NDM-1 mutants revealed that mutations in leucine residues can modify the hydrolytic profile of the enzyme against certain beta-lactams, with L218T and L221T showing significant reduction in hydrolysis efficiency. The stability of the mutants was explored through thermofluor assay, showing NDM-1 and L218T to be the most stable enzymes. Molecular dynamic studies justified differences in kinetic behavior observed among the mutants.
Article
Biochemistry & Molecular Biology
Le Zhai, Yue Jiang, Yang Shi, Miao Lv, Ya-Li Pu, Hua-Lei Cheng, Jia-Yu Zhu, Ke-Wu Yang
Summary: The irregular use of antibiotics has led to the development of antibiotic-resistant bacteria, specifically metallo-beta-lactamases. This study identified eight compounds that have strong inhibitory effects on NDM-1, with one compound being the most effective inhibitor. The presence of a hydroxyl group in the compounds was found to improve their inhibitory activity. Additionally, these compounds demonstrated antibacterial effects on NDM-1-producing bacteria and showed low cytotoxicity in cell experiments.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Radhika Mehta, Dann D. Rivera, David J. Reilley, Dominique Tan, Pei W. Thomas, Abigail Hinojosa, Alesha C. Stewart, Zishuo Cheng, Caitlyn A. Thomas, Michael W. Crowder, Anastassia N. Alexandrova, Walter Fast, Emily L. Que
Summary: The development of a fluorescent probe that reports on the metalation state of NDM within Escherichia coli provides a novel tool to study metal ion sequestration in host-pathogen interactions. The probe selectively coordinates the dizinc metal cluster of NDM and offers a way to monitor the enzyme's response to metal ions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Health Care Sciences & Services
Narcisa Muresu, Giovanna Deiana, Marco Dettori, Alessandra Palmieri, Maria Dolores Masia, Andrea Cossu, Cristina D'Avino, Illari Sechi, Arcadia Del Rio, Andrea Piana, Paolo Castiglia
Summary: The spread of multi-drug resistant organisms (MDROs) is increasing globally. This report presents two independent cases of patients from Ukraine infected with Carbapenemase-producing Klebsiella pneumoniae, and the infection prevention control (IPC) strategies implemented to prevent further contamination. These cases highlight the importance of early recognition of multidrug-resistant bacteria, effective inter-hospital communication, antimicrobial stewardship protocols, and adequate IPC policies. Improvement in screening procedures is necessary to prevent potential nosocomial outbreaks and endemization.
Article
Chemistry, Multidisciplinary
Katarzyna Palica, Manuela Voracova, Susann Skagseth, Anna Andersson Rasmussen, Lisa Allander, Madlen Hubert, Linus Sandegren, Hanna-Kirstirep Schroder Leiros, Hanna Andersson, Mate Erdelyi
Summary: Infectious diseases remain a major concern for public health in the 21st century, and the development of antimicrobial resistance by microbes is a significant problem. The study found that phosphonamidate compounds have the potential to become a new generation of antibiotic therapeutics to combat metallo-beta-lactamase-resistant bacteria.
Article
Biochemistry & Molecular Biology
Lalitha Cheepurupalli, Aathithya Diaz, Adithya Conjeevaram Gopal, Sudarshan Singh Rathore, Vigneshwar Ramakrishnan, Jayapradha Ramakrishnan
Summary: The increase in drug resistance poses a major threat to public health, with carbapenem-resistant bacteria being a significant concern leading to higher morbidity and mortality rates. Inhibiting the activity of New Delhi metallo-beta-lactamase-1 is seen as a potential way to treat multidrug-resistant pathogens. The study identified potential inhibitors for New Delhi metallo-beta-lactamase-1, providing insights into novel treatment strategies for combating drug resistance.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Van-Thanh Tran, Viet-Hung Tran, Dac-Nhan Nguyen, Tran-Giang-Son Do, Thanh-Phuong Vo, Thi-Thao-Nhung Nguyen, Phuong Nguyen Hoai Huynh, Khac-Minh Thai
Summary: Antibiotic resistance is becoming more critical due to the evolving hydrolysis enzymes of bacteria, especially the NDM-1 enzyme which can hydrolyze various antibiotics and inhibitors. This study aims to evaluate the influence of different mutations on the effectiveness of antibiotics and beta-lactamase inhibitors, and the results suggest that substitutions at residues 122 and 124 have the most significant impact on the binding ability of NDM-1 towards inhibitors and antibiotics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Yu-Shan Huang, Wan-Chen Tsai, Jia-Jie Li, Pao-Yu Chen, Jann-Tay Wang, Ying-Tsong Chen, Feng-Jui Chen, Tsai-Ling Lauderdale, Shan-Chwen Chang
Summary: New Delhi metallo-beta-lactamase (NDM) is the most prevalent carbapenemase among carbapenemase-producing Escherichia coli (CPEc) in Taiwan, with IncX3 plasmid and globally distributed strain ST410 potentially contributing to its rapid dissemination.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Analytical
Hongyu Gan, Yaowen Liang, Yun Tang, Manna Huang, Yiqian Wan
Summary: A practical electrochemical method was established to determine the inhibitory activity of New Delhi metallo-beta-lactamase-1 (NDM-1) inhibitors, using a bare pencil graphite electrode (PGE) as the working electrode and imipenem as the substrate. The results were consistent with those from the UV-vis high-throughput assay method.
MICROCHEMICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Ping Zeng, Qipeng Cheng, Lanhua Yi, Sharon Shui Yee Leung, Sheng Chen, Kin-Fai Chan, Kwok-Yin Wong
Summary: In this study, a small peptide library was constructed by capping a macrolactam ring at the C-terminus of a designed peptide. Eight different peptides with aspartic acid-rich macrolactam rings were found to exhibit improved antibacterial activities, and mechanistic studies revealed their mode of action.
BIOORGANIC CHEMISTRY
(2023)
Article
Food Science & Technology
Yan Li, Zhiqiang Wang, Huiyue Dong, Mianzhi Wang, Shangshang Qin, Sheng Chen, Ruichao Li
Summary: Six tet(X4)-positive Klebsiella pneumoniae strains were isolated from pork samples in China, one of which was hypermucoviscous and hypervirulent. The tet(X4) gene was located on a plasmid with a similar structure to blaKPC-2-positive plasmids in hvKp, and it could be transferred to E. coli and ST11 hvKp without a significant fitness cost and persist stably. This is the first report of tet(X4)-positive hvKp in animals, highlighting the urgent need for global surveillance in clinical and animal farming settings.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2023)
Article
Microbiology
Yating Xu, Zhiwei Zheng, Lianwei Ye, Edward Wai-chi Chan, Sheng Chen
Summary: This study investigated the prevalence of qnrVC genes in foodborne Vibrio strains collected in Shenzhen, China, from August 2015 to April 2017. The presence of qnrVC genes was shown to enhance ciprofloxacin resistance in Vibrio strains. Mutations in the gyrA and parC genes were commonly associated with ciprofloxacin resistance. The study also found 14 variant genes containing novel mutations, with 85.7% being qnrVC5-like alleles.
MICROBIOLOGICAL RESEARCH
(2023)
Article
Nutrition & Dietetics
Haicui Wu, Wenxiu Zhang, Mingyue Huang, Xueying Lin, Jiachi Chiou
Summary: Long-term consumption of a high-fat diet can lead to neurobehavioral deterioration through the gut-brain axis.
Article
Biochemistry & Molecular Biology
Leo Man-Yuen Lee, Zhi-Qiang Lin, Lu-Xi Zheng, Yi-Fan Tu, Yik-Hing So, Xiu-Hua Zheng, Tie-Jun Feng, Xi-Yue Wang, Wai-Ting Wong, Yun-Chung Leung
Summary: Growing evidence shows that restricting amino acid intake can reverse obesity by reducing adipose tissue mass. Amino acids not only serve as building blocks for proteins but also play a role as signaling molecules in various biological processes. Understanding how adipocytes respond to changes in amino acid levels is crucial for studying obesity and developing potential treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Environmental
Wanyun He, Mingyi Gao, Luchao Lv, Jing Wang, Zhongpeng Cai, Yuman Bai, Xun Gao, Guolong Gao, Wenxian Pu, Yanxiang Jiao, Miao Wan, Qianhua Song, Sheng Chen, Jian-Hua Liu
Summary: Although not approved for animal use, carbapenems have been increasingly detected in farm animals. This study investigated NPB recovered from chicken feces and environmental samples in three broiler farms. The results showed a high prevalence of NPB carrying the blaNDM gene, indicating persistent contamination and transmission within the farm system. Strict control measures are required to prevent the spread of animal-borne NPB to the environment and community.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Food Science & Technology
Lanhua Yi, Ping Zeng, Jitao Tang, Junhe Ren, Kaifang Zeng, Sheng Chen
Summary: The role of Proteus mirabilis in food safety was previously unknown. Three P. mirabilis strains (swupm1, swupm2, and swupm3) isolated from fresh-cut fruits differed in swarming motility, with swupm1 and swupm2 exhibiting the characteristic bull's-eye phenotype. These strains grew faster and produced stronger biofilm than swupm3. Additionally, they were multidrug-resistant and highly virulent in Galleria mellonella, with swupm1 being the most virulent. P. mirabilis was found to survive in fresh-cut cantaloupe at 4 degrees C and accelerate the decay of fresh-cut fruits at 25 degrees C. The volatile components of fresh-cut cantaloupe were dramatically changed by P. mirabilis strain swupm1.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2023)
Article
Infectious Diseases
Yanyan Zhang, Xuemei Yang, Congcong Liu, Ling Huang, Lingbin Shu, Qiaoling Sun, Hongwei Zhou, Yonglu Huang, Chang Cai, Xiaoyan Wu, Sheng Chen, Rong Zhang
Summary: This study investigated the prevalence and characteristics of OXA-232 type carbapenemase in Zhejiang Province, China from 2018 to 2021. The results showed that OXA-232 is the most prevalent OXA-48-like derivative, and ST15 K. pneumoniae isolates are the major carriers. The transmission of ColKP3-type plasmid to E. coli highlighted the importance of understanding the transmission mechanism to prevent the spread of OXA-232 to other species.
INFECTIOUS DISEASES OF POVERTY
(2023)
Article
Microbiology
Xuemei Yang, Xiaoxuan Liu, Edward Wai-Chi Chan, Rong Zhang, Sheng Chen
Summary: Klebsiella pneumoniae has become a major bacterial pathogen in hospitals, with a high mortality rate. Factors contributing to its virulence are the overproduction of capsular polysaccharide (CPS) and the hypermucoviscosity (HMV) phenotype. This study investigated the functional characteristics of plasmid-borne rmp homologues in clinical hypervirulent K. pneumoniae strains. The results showed that the rmp homologues play a key role in regulating the HMV phenotype and CPS production in K. pneumoniae.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Xiaobo Liu, Ruichao Li, Edward Wai-Chi Chan, Sheng Chen
Summary: Bacterial antimicrobial resistance, especially phenotypic resistance to multiple drugs (MDR), has posed a serious threat to public health worldwide. Understanding the mechanisms of transmission of multidrug resistance encoding plasmids in Enterobacterales is crucial for controlling the spread of MDR pathogens. In this study, plasmids in an Escherichia coli strain isolated from chicken meat samples were characterized, revealing the presence of multiple antimicrobial resistance genes and the potential for transmission of resistance determinants.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Yonggang Zhao, Dingqiang Chen, Kaichao Chen, Miaomiao Xie, Jiubiao Guo, Edward Wai Chi Chan, Lu Xie, Jingbo Wang, Enqi Chen, Sheng Chen, Weijun Chen, Lars Jelsbak
Summary: By sequencing and analyzing the genomes of 416 Pseudomonas aeruginosa strains from hospitals in China, the genetic, phenotypic, and transmission characteristics of carbapenem-resistant strains were elucidated, and the molecular signatures responsible for the increased prevalence of CRPA infections in China were identified. These findings may provide new insight into the development of effective strategies for worldwide control of CRPA and minimize the occurrence of untreatable infections in clinical settings.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Applied
Ping Zeng, Pengfei Zhang, Lanhua Yi, Kwok-Yin Wong, Sheng Chen, Kin-Fai Chan, Sharon Shui Yee Leung
Summary: Researchers have developed a new antibacterial peptide (zp80r) by modifying the structure of a reported peptide. This peptide has shown promise in reducing the quantity of pathogenic bacteria on the surface of pork products, making it a potential candidate for controlling foodborne pathogens during storage.
Article
Microbiology
Zhiwei Zheng, Lizhang Liu, Lianwei Ye, Yating Xu, Sheng Chen
Summary: A nationwide survey in China identified seven blaIMP-4-carrying CRKP isolates, which exhibited MDR and were linked to different regions. Genetic analysis revealed significant variation among these CRKP strains and identified multiple resistance factors. This highlights the need for expanded surveillance and control measures to prevent dissemination of CRKP strains and improve antibiotic stewardship and infection control.
MICROBIOLOGICAL RESEARCH
(2023)
Article
Microbiology
Yating Xu, Zhiwei Zheng, Lianwei Ye, Edward Wai-Chi Chan, Sheng Chen
Summary: A new quinolone resistance gene, qnrS, was found in foodborne Vibrio spp., which could mediate resistance to ciprofloxacin and cephalosporins. The qnrS2 gene could be found on both the chromosome and plasmids, with the pAQU-type qnrS2-bearing conjugative plasmids able to mediate resistance to both ciprofloxacin and cephalosporins. Transmission of this plasmid among Vibrio spp. may lead to the emergence of multidrug-resistant pathogens.
MICROBIOLOGY SPECTRUM
(2023)
Letter
Biochemistry & Molecular Biology
Qi Xu, Miaomiao Xie, Xiaoxuan Liu, Heng Heng, Han Wang, Chen Yang, Edward Wai-Chi Chan, Rong Zhang, Guan Yang, Sheng Chen
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)