Simultaneous removal of ammonia nitrogen, sulfamethoxazole, and antibiotic resistance genes in self-corrosion microelectrolysis-enhanced counter-diffusion biofilm system

Article

Author: Zhang, Han ; Wang, Qingru ; Cheng, Yufei ; Han, Xiaohang ; Liang, Heng ; Zhao, Rui ; Bai, Langming ; Li, Guibai ; Xue, Ying ; Zhu, Junqin

A self-corrosion microelectrolysis (SME)-enhanced membrane-aerated biofilm reactor (eMABR) was developed for the removal of pollutants and reduction of antibiotic resistance genes (ARGs). Fe²⁺ and Fe³⁺ formed iron oxides on the biofilm, which enhanced the adsorption and redox process. SME can induce microorganisms to secrete more extracellular proteins and up-regulate the expression of ammonia monooxygenase (AMO) (0.92 log₂). AMO exposed extra binding sites (ASP-69) for antibiotics, weakening the competition between NH₄⁺-N and sulfamethoxazole (SMX). The NH₄⁺-N removal efficiency in the S-eMABR (adding SMX and IC) increased by 44.87 % compared to the S-MABR (adding SMX). SME increased the removal performance of SMX by approximately 1.45 times, down-regulated the expressions of sul1 (-1.69 log₂) and sul2 (-1.30 log₂) genes, and controlled their transfer within the genus. This study provides a novel strategy for synergistic reduction of antibiotics and ARGs, and elucidates the corresponding mechanism based on metatranscriptomic and molecular docking analyses.

04 Sep 2024·Biological and Pharmaceutical Bulletin

Salmon Milt Extract Suppresses Glucose Uptake by Downregulating SGLT1 and GLUT2 Expression in Caco-2 Cells

Article

Author: Okamoto, Keisuke ; Mori, Takao ; Furugen, Ayako ; Ishihara, Komei ; Narumi, Katsuya ; Taguchi, Rin ; Sato, Taichi ; Kobayashi, Masaki ; Satoh, Hiroshi

Salmon milt extract (SME) is rich in nucleotides, especially deoxyribonucleoside monophosphates (dNMPs), which has the potential to exert anti-obesity effects. Sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) are responsible for absorbing sugar from the small intestine. The purpose of this study was to examine the effects of SME on the functions of SGLT1 and GLUT2 and elucidate the mechanisms underlying the inhibition of glucose absorption by SME. We investigated the effect of SME on the expression and function of intestinal glucose transporters, using differentiated Caco-2 cells. SME treatment decreased the expression SGLT1 and GLUT2 mRNA and protein in Caco-2 cells. [¹⁴C]-Labelled methyl-α-D-glucopyranoside and [³H]-labelled 2-deoxy-D-glucose (DG) uptake into Caco-2 cells was significantly reduced by SME treatment. Similarly, the dNMP mixture containing the four mononucleotides 2'-deoxyadenosine 5'-monophosphate (dAMP), 2'-deoxyguanosine 5'-monophosphate (dGMP), 2'-deoxycytidine 5'-monophosphate (dCMP), and 2'-deoxythymidine 5'-monophosphate (dTMP) decreased SGLT1 and GLUT2 expression. dNMP mixture-induced reduction in the mRNA expression of these transporters was suppressed when exposed to the mixture without dTMP. Furthermore, dNMP mixture-induced alterations in the expression of hepatocyte nuclear factor (HNF)-1α and HNF1β, which have been characterized as modulators of both transporters also showed a similar trend. dTMP treatment alone decreased GLUT2 expression, resulting in reduced [³H] DG uptake by Caco-2 cells. SME decreased the expression of HNF1α, HNF1β, and its targets SGLT1 and GLUT2, resulting in reduced glucose uptake by Caco-2 cells. In addition, our results revealed that dTMP plays an important role in suppressing the expression of intestinal glucose transporters.

01 Sep 2024·Bioorganic Chemistry

Chemical sensors for the early diagnosis of bacterial resistance to β-lactam antibiotics

Review

Author: González-Bello, Concepción ; Canabal, Rafael

β-Lactamases are bacterial enzymes that inactivate β-lactam antibiotics and, as such, are the most prevalent cause of antibiotic resistance in Gram-negative bacteria. The ever-increasing production and worldwide dissemination of bacterial strains producing carbapenemases is currently a global health concern. These enzymes catalyze the hydrolysis of carbapenems - the β-lactam antibiotics with the broadest spectrum of activity that are often considered as drugs of last resort. The incidence of carbapenem-resistant pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and carbapenemase or extended spectrum beta-lactamase (ESBL)-producing Enterobacterales, which are frequent in clinical settings, is worrisome since, in some cases, no therapies are available. These include all metallo-β-lactamases (VIM, IMP, NDM, SMP, and L1), and serine-carbapenemases of classes A (KPC, SME, IMI, and GES), and of classes D (OXA-23, OXA-24/40, OXA-48 and OXA-58). Consequently, the early diagnosis of bacterial strains harboring carbapenemases is a pivotal task in clinical microbiology in order to track antibiotic bacterial resistance and to improve the worldwide management of infectious diseases. Recent research efforts on the development of chromogenic and fluorescent chemical sensors for the specific and sensitive detection and quantification of β-lactamase production in multidrug-resistant pathogens are summarized herein. Studies to circumvent the main limitations of the phenotypic and molecular methods are discussed. Recently reported chromogenic and fluorogenic cephalosporin- and carbapenem-based β-lactamase substrates will be reviewed as alternative options to the currently available nitrocefin and related compounds, a chromogenic cephalosporin-based reagent widely used in clinical microbiology laboratories. The scope of these new chemical sensors, along with the synthetic approaches to synthesize them, is also summarized.

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Indication	Highest Phase	Country/Location	Organization	Date
MRSA - Methicillin resistant Staphylococcus aureus infection	Preclinical	CN	Botanic Century (Beijing) Co. Ltd.	23 Aug 2022

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