Article
Infectious Diseases
Hongyu Chen, Huirong Mai, Bruno Lopes, Feiqiu Wen, Sandip Patil
Summary: This study identified carbapenem- and colistin-resistant multi-drug resistant Pseudomonas aeruginosa in paediatric patients with leukaemia in Shenzhen, China. It highlights the need for continuous surveillance of high-risk clones of multi-drug resistant P. aeruginosa. Prudent use of antibiotics based on local antimicrobial susceptibility and clinical characteristics can help in reducing mortality in immunocompromised patients.
INFECTION AND DRUG RESISTANCE
(2022)
Review
Biochemistry & Molecular Biology
Yongqiang Yang, Yu-Hang Yan, Christopher J. Schofield, Alan McNally, Zhiyong Zong, Guo-Bo Li
Summary: Resistance to beta-lactam antibiotics is a growing concern due to the spread of serine-beta-lactamases (SBLs) and metallo-beta-lactamases (MBLs), which efficiently break down beta-lactam antibiotics. While inhibitors for SBLs have been successful in clinical use, there are currently no inhibitors for MBLs. MBLs are particularly worrisome as they can break down most beta-lactam antibiotics and are rapidly disseminating across bacterial species worldwide.
TRENDS IN MICROBIOLOGY
(2023)
Article
Infectious Diseases
Yue Li, Yiwei Zhu, Wanqing Zhou, Zhongju Chen, Robert A. Moran, Huanhuan Ke, Yu Feng, Willem van Schaik, Han Shen, Jingshu Ji, Zhi Ruan, Xiaoting Hua, Yunsong Yu
Summary: This study characterized AFM-2 and AFM-3 metallo-beta-lactamase from clinical Pseudomonas aeruginosa isolates. The results showed that these enzymes exhibited beta-lactamase activity comparable to NDM-1, and the co-carriage of bla(AFM) and bla(KPC) genes rendered P. aeruginosa resistant to antipseudomonal beta-lactams. Furthermore, the association of bla(AFM) genes with translocatable genetic elements and plasmids highlighted their potential for dissemination.
CLINICAL MICROBIOLOGY AND INFECTION
(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
Infectious Diseases
Melise Chaves Silveira, Rodolpho Mattos Albano, Claudio Marcos Rocha-de-Souza, Robson Souza Leao, Elizabeth Andrade Marques, Renata Cristina Picao, Gabriela Bergiante Kraychete, Ivson Cassiano de Oliveira Santos, Thamirys Rachel Tavares e Oliveira, Camila Bastos Tavares-Teixeira, Ana Paula D' Alincourt Carvalho-Assef
Summary: The high rates of carbapenem resistance among Brazilian Pseudomonas aeruginosa isolates are mainly associated with the clone ST277 producing the carbapenemase SPM-1. The complete genetic composition of a IncP plasmid harboring blaKPC-2 in isolates of this endemic clone carrying chromosomal blaSPM-1 was described using whole genome sequencing. These results confirm the association of these two carbapenemases in ST277 and also describe the genetic composition of a novel blaKPC-2-plasmid. Considering the fact that this association occurs in a high-risk clone, monitoring the dissemination of this plasmid should be a public health concern.
INFECTION GENETICS AND EVOLUTION
(2022)
Article
Pharmacology & Pharmacy
Yan Guo, Hongtao Liu, Mengge Yang, Rui Ding, Yawen Gao, Xiaodi Niu, Xuming Deng, Jianfeng Wang, Haihua Feng, Jiazhang Qiu
Summary: The study identified dexrazoxane, embelin, candesartan cilexetil, and nordihydroguaiaretic acid as promising carbapenem adjuvants against metallo-β-lactamase-producing carbapenem-resistant bacterial pathogens. These drugs inhibit the activity of metallo-β-lactamases and show in vitro synergistic bactericidal effect with meropenem.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Microbiology
Melina M. B. Martinez, Robert A. Bonomo, Alejandro J. Vila, Paulo C. Maffia, Lisandro J. Gonzalez
Summary: The emergence and dissemination of carbapenemase-producing Gram-negative bacteria pose a major public health threat worldwide. NDM-1, a potent carbapenem-hydrolyzing enzyme, is rapidly spreading and evolving with the ability to be secreted into outer membrane vesicles (OMVs). These OMVs act as vehicles for local dissemination, protecting susceptible bacteria against meropenem. The protective effect correlates with the amount of NDM-1 secreted into vesicles, suggesting a role in bacterial community establishment and antibiotic resistance dissemination.
Article
Microbiology
Xiaoxia Gu, Mengzhu Zheng, Lixia Chen, Hua Li
Summary: This article summarizes NDM-1 inhibitors developed since 2018, classifies these compounds by chemical scaffolds, and points out inconsistencies and notable problems in these studies, which are expected to benefit future research.
MICROBIOLOGICAL RESEARCH
(2022)
Review
Microbiology
Pabllo Antonny Silva Dos Santos, Marcos Jesse Abrahao Silva, Maria Isabel Montoril Gouveia, Luana Nepomuceno Gondim Costa Lima, Ana Judith Pires Garcia Quaresma, Patricia Danielle Lima De Lima, Danielle Murici Brasiliense, Karla Valeria Batista Lima, Yan Correa Rodrigues
Summary: The purpose of this study was to describe the prevalence of M beta L-producing Pseudomonas aeruginosa (PA) isolates and the frequency of bla(SPM-1) in M beta L-PA-producing isolates in Brazil. The findings showed that M beta L-PA and SPM-1 isolates were relatively common among individuals in Brazil. Further research is needed to identify risk factors, reservoirs, transmission pathways, and the origin of infection.
Article
Microbiology
Qian Wang, Kai Peng, Yuan Liu, Xia Xiao, Zhiqiang Wang, Ruichao Li
Summary: The emergence and transmission of novel antimicrobial resistance genes, such as the plasmid-encoded RND efflux pump TMexCD1-TOprJ1, pose a great threat to global public health by reducing the sensitivity of multiple antimicrobials. This study identified a pandrug-resistant Proteus mirabilis isolate harboring a novel tmexCD3-toprJ3 gene cluster located on SXT/R391 ICE, expanding current knowledge on the transfer mechanisms of tmexCD1-toprJ1-like gene clusters among P. mirabilis isolates. Further genomic epidemiology investigations are warranted.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Heng Cai, Yiwei Zhu, Dandan Hu, Yue Li, Sebastian Leptihn, Belinda Loh, Xiaoting Hua, Yunsong Yu
Summary: Multiple carbapenem-resistant strains of Pseudomonas aeruginosa were isolated from the same patient in a hospital in China, one of which carried a non-transferable plasmid with a novel resistance gene segment. Additionally, a study on the chromosomes of P. aeruginosa strains with the same sequence type identified an integrative and conjugative element adjacent to a prophage, mediating resistance to multiple antibiotics. This study sheds light on the acquisition of antibiotic resistance in P. aeruginosa facilitated by mobile genetic elements.
FRONTIERS IN MICROBIOLOGY
(2021)
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
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, Medicinal
Kalyan C. Nagulapalli Venkata, Morgan Ellebrecht, Siddharth K. Tripathi
Summary: Antimicrobial stewardship is crucial in treating bacterial infections; NDM-1 is an enzyme that enables bacterial resistance; extensive research has been invested in search of NDM-1 inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Changrui Qian, Hongmao Liu, Jiawei Cao, Yongan Ji, Wei Lu, Junwan Lu, Aifang Li, Xinyi Zhu, Kai Shen, Haili Xu, Qianqian Chen, Wangxiao Zhou, Hongyun Lu, Hailong Lin, Xueya Zhang, Qiaoling Li, Xi Lin, Kewei Li, Teng Xu, Mei Zhu, Qiyu Bao, Hailin Zhang
Summary: The study found different types of floR genes in Pseudomonas aeruginosa, with floR-T1 being the most prevalent. A novel floR variant, floR-T2, showed lower identity with other FloR proteins and could be induced by florfenicol or chloramphenicol. These floR variants play an important role in host resistance and spread, potentially related to the Tn4371 family ICE.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
