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JOURNAL OF BACTERIOLOGY · 2022 · IF 3.476

Genetic Signatures from Adaptation of Bacteria to Lytic Phage Identify Potential Agents to Aid Phage-Killing of Multidrug-Resistant Acinetobacter baumannii

Greater Kayode Oyejobi,Dongyan Xiong,Mengjuan Shi,Xiaoxu Zhang,Hang Yang,Heng Xue,Faith Ogolla,Hongping Wei

With the increasing morbidity and mortality rates associated with multidrug-resistant bacteria, interest in bacteriophage therapy has been revived. However, bacterial resistance to phage infection threatens the usefulness of phage therapy, especially its inclusion in modern medicine. Multidrug-resistant Acinetobacter baumannii is a top-priority pathogen requiring urgent intervention and new therapeutic approaches, such as phage therapy. Here, we experimentally adapted A. baumannii WHG40004 to its lytic phage P21 and thereafter isolated a phage-resistant bacterial mutant, named Ev5-WHG. We then aimed to identify potential agents to aid phage killing of Ev5-WHG by analyzing its genome and that of the wild-type strain. The enriched Gene Ontology (GO) analysis based on genetic alterations in minor alleles and mutations showed that pathways such as zinc ion transport and cell membrane synthesis could play certain roles in phage resistance. Remarkably, the combination of zinc acetate and P21 showed increased bactericidal effect on Ev5-WHG. Significantly also, we showed that P21 completely prevented the growth of wild-type WHG40004 in the presence of antibiotics (meropenem and imipenem). The results from this study indicate that the analysis of phage resistance signatures during adaptation of bacteria to a lytic phage can inform the choice of agents to work cooperatively with phage to limit and/or reverse resistance. This approach could be important for guiding future successful phage therapy.IMPORTANCE Bacteriophages have proven very useful as alternative therapeutic agents in combating multidrug-resistant bacterial infections; however, bacterial resistance to phages threatens their use. In this study, we showed a new strategy of leveraging genetic signatures that accompany phage resistance in bacteria to predict agents that can be used with lytic phages to combat multidrug-resistant Acinetobacter baumannii. Significantly, this approach was helpful in suggesting the use of zinc acetate to reduce resistance in phage-resistant bacteria, as well as the use of phage with antibiotics meropenem and imipenem to prevent resistance in a wild-type strain of multidrug-resistant A. baumannii. The approach of this study will be helpful for improving the outcome of phage therapy and in overcoming antimicrobial resistance.

CAS / MDL: 119478-56-7
研究领域: 微生物学 · 基因组学 · 抗菌素耐药性 · 噬菌体疗法 · 细菌遗传学
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CHEMICAL ENGINEERING JOURNAL · 2019 · IF 8.355

Oxidative degradation of chloroxylenol in aqueous solution by thermally activated persulfate: Kinetics, mechanisms and toxicities

Yujiao Sun,Juanjuan Zhao,Bo-Tao Zhang,Jie Li,Yongbin Shi,Yang Zhang

Chloroxylenol (PCMX) degradation by thermally activated persulfate (TAP) in aqueous solution and the toxicity changes of the system were investigated. PCMX oxidative degradation followed a pseudo-first-order kinetic model. The apparent activation energy of PCMX degradation was calculated to be 130.0 kJ·mol −1 , according to the Arrhenius equation, over the range of 30–60 °C. The PCMX degradation efficiency was significantly increased with the reaction temperature and initial persulfate concentration, while it was not influenced by the initial solution pH or water matrices. The hydroxyl radicals and sulfate radicals (SRs) in the TAP system were proved by electron paramagnetic resonance (EPR) spectroscopy. SRs were the predominant radical species at neutral pH, as verified by radical scavenging tests. The possible degradation pathways, including electron transfer, dechlorination, aromatic ring oxidation, side-chain oxidation and a subsequently opening aromatic ring, were proposed based on intermediate detection. The acute toxicity and genotoxicity of the PCMX degradation solution were estimated by the Escherichia coli and Acinetobacter baylyi ADP1_recA_lux bioreporter, respectively. The results suggested that TAP was a feasible and environmentally friendly technology for PCMX-contaminated water remediation.

CAS / MDL: 64-17-5 75-65-0
研究领域: 环境科学 · 化学工程 · 水处理 · 毒理学 · 环境化学
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FOOD CHEMISTRY · 2023 · IF 8.8

A SERS bioassay based on vancomycin-modified PEI-interlayered nanocomposite and aptamer-functionalized SERS tags for synchronous detection of Acinetobacter baumannii and Klebsiella pneumoniae

Clement Yaw Effah,Lihua Ding,Longlong Tan,Sitian He,Xiang Li,Huijie Yuan,Yi Li,Shaohua Liu,Tongwen Sun,Yongjun Wu

Klebsiella pneumoniae ( KP ) and Acinetobacter baumannii ( AB ) are two important gram-negative bacteria that cause pneumonia and have been recently known to be associated with food. The rapid detection of these pathogens in food is important to minimize their colonization of the gut and stop new threats of the disease from spreading across the food chain. Herein, a double-edged sword aptasensor was developed for the synchronous detection of KP and AB in food and clinical samples. A highly sensitive, selective, specific, and synchronous detection of the target bacteria was achieved, and the limit of detection (LOD) was 10 cells/mL with a liner range of 50 to 10 5 cells/mL. The total assay time was 1.5 h. This study does not only provide a new tool for the detection of the target bacteria, but also serves as a promising tool for food safety and pneumonia diagnosis.

研究领域: 分析化学 · 生物传感器 · 食品安全 · 微生物学 · 医学诊断
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Biomed Research International · 2022 · IF 3.246

In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β-Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo-β-lactamase-1 (NDM-1)

Aparna Vasudevan,Dinesh Kumar Kesavan,Liang Wu,Zhaoliang Su,Shengjun Wang,Mohan Kumar Ramasamy,Waheeta Hopper,Huaxi Xu

Antibiotic resistance is one of the significant problems globally; there is an increase in resistance with introducing every new class of antibiotics. Further, this has become one of the reasons for arising of new resistance mechanisms in Acinetobacter baumannii. In this study, we have screened natural compounds as a possible inhibitor against the NDM-1 β-lactamase enzyme from A. baumannii using a combination of in silico methods and in vitro evaluation. The database of natural compounds was screened against NDM-1 protein, using Glide docking, followed by QM-polarised ligand docking (QPLD). When the screened hits were validated in vitro, withaferin A and mangiferin had good IC50 values in reducing the activity of NDM-1 enzymes, and their fractional inhibitory concentration index (FICI) was ascertained in combination with imipenem. The withaferin A and mangiferin-NDM-1 docking complexes were analyzed for structural stability by molecular dynamic simulation analysis using GROMACS for 100 ns. The molecular properties of the natural compounds were then calculated using density functional theory (DFT). Withaferin A and mangiferin showed promising inhibitory activity and can be a natural compound candidate inhibitor synergistically used along with carbapenems against NDM-1 producing A. baumannii.

CAS / MDL: 6381-92-6 41906-86-9
研究领域: 微生物学 · 药物化学 · 计算生物学
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