Microorganisms
·
2023
·Vol. 11
·期 2
·533
·
IF 4.5
Aishwarya Murali,Franziska Maria Zickgraf,Philipp Ternes,Varun Giri,Hunter James Cameron,Saskia Sperber,Volker Haake,Peter Driemert,Hennicke Kamp,Dorothee Funk Weyer,Shana J. Sturla,Ivonne M. G. M. Rietjens,Bennard van Ravenzwaay
An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies.
研究领域:
微生物学
·
药理学
·
代谢组学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Fábio de Souza Barbosa,Leonardo Capra Pezzi,Fávero Reisdorfer Paula,Sarah Eller,Elfrides E.S. Schapoval,Tiago Franco de Oliveira,Andreas S.L. Mendez
In the present study, the stability of the antibiotic doripenem was evaluated with a focus on identifying the degradation products generated. For this, a method by LC-ESI-Q-TOF was developed and validated. Also, as an auxiliary tool in the identification of degradation products, Zeneth 7 software was used in the prediction of drug degradation in silico . Under stress conditions six degradation products were detected and based on the literature and MS 2 analyzes, their structures were proposed. Under hydrolytic conditions, in acid, neutral and alkaline media, the major degradation product was formed through the cleavage of the β -lactam ring. In neutral hydrolysis, the formation of two drug dimers was also observed. Oxidation of the drug using H 2 O 2 (3%) led to the formation of three degradation products, not yet reported in the literature, generated by oxidation of the thioether group and by decarboxylation reaction. The most probable elemental compositions for degradations products were obtained with a high degree of confidence, where the error between the masses observed and calculated was less than 5 ppm. The stability of doripenem after reconstitution was studied in conditions that simulate its clinical use. At room temperature, the drug demonstrated a similar degradation profile when prepared using 0.9% NaCl and 5% glucose for infusion, keeping its content > 90% for at least 8 h, and the LC-ESI-Q-TOF analyzes detected the formation of three degradation products, highlighting two different dimers. Finally, all the data generated helps to understand the degradation behavior of doripenem and its important antibiotic class.
研究领域:
药物化学
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分析化学
·
药物稳定性
✓ 已验证
DOI
高影响因子
Science Advances
·
2025
·Vol. 11
·期 43
·
IF 12.5
Hao Tang,Xiaomeng Zhao,Mengsi Sun,Jie Qi,Zhihao Huang,Yihang Zhu,Yingmin Zeng,Yong Xia,Zhi Luo,Xingyu Jiang
No clinically available antibiotic adjuvants can overcome metallo-β-lactamase (MBL) resistance in carbapenem-resistant Gram-negative ESKAPE pathogens. Divalent cations in MBL and quasicrystalline lipopolysaccharides (LPS) are key determinants of acquired and intrinsic resistance in these bacteria. Chemically depriving these cations would block multiple resistance pathways simultaneously and restore carbapenem susceptibility. Here, we chemically engineer a class of anionic adjuvants to tailor their interactions with MBL, enhancing the enzymatic inhibition by up to ~5885-fold compared to parent compounds. An orthogonal screen identifies the tiopronin-engineered anionic adjuvant (TINA), which achieves complete rescue of all tested carbapenems against diverse New Delhi metallo-β-lactamase-1–producing Gram-negative ESKAPE bacteria. TINA targets both MBL and LPS, depriving divalent cations to inactivate MBL and damage membrane collaboratively while also preventing resistance evolution. Moreover, TINA’s anionic nature minimizes serum adsorption, enabling safe and effective in vivo treatment of bacterial pneumonia. This work provides an innovative chemical biology strategy leveraging anionic materials to combat superbugs globally.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Xuan Ma,Yue Wang,Wenting Wang,Jake Heinlein,Lisa D. Pfefferle,Xuemeng Tian
In this study, a facile method has been developed to synthesize a novel type of porous magnetic molecularly imprinted polymers (Fe 3 O 4 -MER-MMIPs) for the selective adsorption and removal of meropenem. The Fe 3 O 4 -MER-MMIPs, with abundant functional groups and sufficient magnetism for easy separation, are prepared in aqueous solutions. The porous carriers reduce the overall mass of the MMIPs, greatly improving their adsorption capacity per unit mass and optimizing the overall value of the adsorbents. The green preparation conditions, adsorption performance, and physical and chemical properties of Fe 3 O 4 -MER-MMIPs have been carefully studied. The developed submicron materials exhibit a homogeneous morphology, satisfactory superparamagnetism (60 emu g −1 ), large adsorption capacity (11.49 mg g −1 ), quick adsorption kinetics (40 min), and good practical implementation in human serum and environmental water. Finally, the protocol developed in this work delivers a green and feasible method for synthesizing highly efficient adsorbents for the specific adsorption and removal of other antibiotics as well.
研究领域:
环境科学
·
材料科学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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