Article
Multidisciplinary Sciences
Jian Ji, Shang Wu, Lina Sheng, Jiadi Sun, Yongli Ye, Yiyun Zhang, Yinzhi Zhang, Yajun Gong, Jianzhong Zhou, Xiulan Sun
Summary: The study utilized the LC-MS/MS metabolomics platform to analyze the metabolic profiles of 138 strains of Salmonella, and found that these profiles were related to the serotypes, sources, processing stages, and antibiotic resistance patterns of the bacteria. Specifically, Salmonella Derby with drug resistance to ceftriaxone exhibited a different metabolic status with changes in glutathione biosynthesis. Exogenous glutathione oxidized or citrulline, but not glutathione reduced, restored the susceptibility of multidrug-resistant Salmonella Derby to ceftriaxone. This study establishes a strategy based on functional metabolomics to manage the survival of antibiotic-resistant bacteria.
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
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
Microbiology
Dennis Nurjadi, Kaan Kocer, Quan Chanthalangsy, Sabrina Klein, Klaus Heeg, Sebastien Boutin
Summary: This study found that the emergence of resistance to Cefiderocol in metallo-beta-lactamase-producing bacteria is facilitated by mutations in the CirA siderophore receptor, which are induced by the New Delhi metallo-beta-lactamase. However, inhibiting the metallo-beta-lactamase activity using dipicolinic acid can successfully prevent the development of Cefiderocol-resistant mutants. Therefore, caution should be taken when using Cefiderocol to treat infections caused by metallo-beta-lactamase-producing bacteria.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Jia-Qi Li, Le-Yun Sun, Zhihui Jiang, Cheng Chen, Han Gao, Jia-Zhu Chigan, Huan-Huan Ding, Ke-Wu Yang
Summary: A new scaffold was constructed for inhibiting NDM-1, showing promising results in combating bacterial infections and providing important insights for the development of anti-NDM-1 drugs.
BIOORGANIC CHEMISTRY
(2021)
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
Biotechnology & Applied Microbiology
Namrata Baruah, Nadim Ahamad, Prolay Halder, Hemanta Koley, Dhirendra S. S. Katti
Summary: The development of biomimetic nanovaccines can provide significant cross-protection against drug-resistant Shigella and protect infants, while also offering a non-invasive route for vaccination.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jia-Zhu Chigan, Zhenxin Hu, Lu Liu, Yin-Sui Xu, Huan-Huan Ding, Ke-Wu Yang
Summary: The superbug infection caused by metallo-beta-lactamases (M beta Ls) has become an urgent health threat. In this study, compounds were synthesized and tested for their inhibitory effect on M beta L NDM-1. Among them, 1e and 1f showed the strongest inhibition, with an IC50 value of 0.02 mu M against NDM-1. This study provides potential lead compounds for further development of clinically useful inhibitors targeting NDM-1.
BIOORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Bing Zhao, Xinhui Zhang, Tingting Yu, Ying Liu, Xiaoling Zhang, Yongfang Yao, Xuejian Feng, Hongmin Liu, Dequan Yu, Liying Ma, Shangshang Qin
Summary: New Delhi metallo-beta-lactamase-1 (NDM-1) poses a threat to public health as it can hydrolyze nearly all beta-lactam antibiotics. In this study, thiosemicarbazone derivatives were evaluated for their potential to treat NDM-1 positive superbugs, with compounds 19bg and 19bh showing promising activity. Molecular docking suggested these compounds may inhibit NDM-1 in an allosteric pocket, potentially offering new treatment options for NDM-1 producing strains.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Biotechnology & Applied Microbiology
Ying Ge, Peng-Wei Kang, Jia-Qi Li, Han Gao, Le Zhai, Le-Yun Sun, Cheng Chen, Ke-Wu Yang
Summary: The study demonstrated that thiosemicarbazones are valuable scaffolds for developing inhibitors of NDM-1 and drug-resistant bacteria carrying NDM-1, and they also exhibit synergistic antimicrobial effects with other antibiotics, showing strong activity against bacteria harboring NDM-1.
JOURNAL OF ANTIBIOTICS
(2021)
Article
Infectious Diseases
Ongwae H. Zachariah, Mwamburi A. Lizzy, Kakai Rose, Mutuku M. Angela
Summary: This study found that approximately 33.1% of faecal samples from children under five years old presenting with diarrhoea at Kapsabet County Referral Hospital in Kenya tested positive for enteric pathogens. Shigella spp. and Campylobacter jejuni exhibited resistance to various antibiotics, highlighting the need for further investigation and development of effective therapeutic alternatives.
BMC INFECTIOUS DISEASES
(2021)
Article
Microbiology
Carola Venturini, Bethany Bowring, Alicia Fajardo-Lubian, Carol Devine, Jonathan Iredell
Summary: The study found that different antibiotics have a significant impact on the gut microbiota of mice, with third-generation cephalosporins causing more severe dysbiosis. Even after the antibiotics are stopped, the gut of mice remains highly susceptible to colonization by antibiotic-resistant enterobacterial pathogens. Co-habitation of untreated mice with treated mice can mitigate the dysbiosis caused by treatment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Alexandra V. Krivitskaya, Maria G. Khrenova
Summary: Penicillin-binding proteins 2 (PBP2) are important enzymes in bacterial cell wall formation and their inhibition is used in treating various diseases. Resistance to the drug ceftriaxone, used for gonorrhea treatment, has increased in PBP2, posing a threat. The study uncovers the inhibition mechanism of ceftriaxone on PBP2 from wild-type and mutant strains of Neisseria Gonorrhoeae. The findings reveal differences in the reaction steps and dynamics, as well as the impact on drug binding affinity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Infectious Diseases
Vivek Kumar Ranjan, Shriparna Mukherjee, Subarna Thakur, Krutika Gupta, Ranadhir Chakraborty
Summary: The study found that the pandrug-resistant strain Pseudomonas sp. MR 02 is able to consume ampicillin for growth, which has significant implications for bioremediation of beta-lactam residues in the environment.
CLINICAL MICROBIOLOGY AND INFECTION
(2021)
Article
Immunology
Radhika Gharpure, Cindy R. Friedman, Veronica Fialkowski, Jennifer P. Collins, Jonathan Strysko, Zachary A. Marsh, Jessica C. Chen, Elizabeth H. Meservey, Azizat A. Adediran, Morgan N. Schroeder, Ashutosh Wadhwa, Kathleen E. Fullerton, Louise Francois Watkins
Summary: A study investigated a multi-drug resistant Shigella outbreak where 4 patients were treated with azithromycin, all of whom experienced treatment failure, with 2 also showing microbiologic failure; 2 patients who received ciprofloxacin treatment also failed. The findings underscore the importance of identifying alternative treatment options for resistant strains.
CLINICAL INFECTIOUS DISEASES
(2022)