Synthesis of β-lactam-zidovudine pronucleosides as potential selective narrow-spectrum antibacterial agents.

Since the discovery of penicillin, the forerunner of the most widely used class of antibiotics ( β-lactams), natural compounds and their derivatives represented a major source of antibacterial therapeutic products whose availability enabled modern medical practices (invasive surgery, organ transplant, .). However, the relentless emergence of resistant bacteria is challenging the long-term efficacy of antibiotics, also decreasing their economic attractiveness for big pharma, leading to a significant decay in antibacterial development in the 21 century and an increased use of last-resort drugs such as carbapenems or colistin.

Can a regulatory control network be used for a territorial monitoring of antimicrobial resistance in water intended for human consumption?

Antimicrobial resistance genes and resistant bacteria could be found in water intended for human consumption (WIHC). In France, although the microbiological quality of WIHC is strictly monitored, antimicrobial resistance is not. The aim of this study is to test the concept of the use of the regulatory surveillance of WIHC to monitor antimicrobial resistance in a French area.

Discovering NDM-1 inhibitors using molecular substructure embeddings representations.

NDM-1 (New-Delhi-Metallo-β-lactamase-1) is an enzyme developed by bacteria that is implicated in bacteria resistance to almost all known antibiotics. In this study, we deliver a new, curated NDM-1 bioactivities database, along with a set of unifying rules for managing different activity properties and inconsistencies. We define the activity classification problem in terms of Multiple Instance Learning, employing embeddings corresponding to molecular substructures and present an ensemble ranking and classification framework, relaying on a k-fold Cross Validation method employing a per fold hyper-parameter optimization procedure, showing promising generalization ability.

Zidovudine-β-Lactam Pronucleoside Strategy for Selective Delivery into Gram-Negative Bacteria Triggered by β-Lactamases.

Addressing antibacterial resistance is a major concern of the modern world. The development of new approaches to meet this deadly threat is a critical priority. In this article, we investigate a new approach to negate bacterial resistance: exploit the β-lactam bond cleavage by β-lactamases to selectively trigger antibacterial prodrugs into the bacterial periplasm.

Optimization of 1,2,4-Triazole-3-thiones toward Broad-Spectrum Metallo-β-lactamase Inhibitors Showing Potent Synergistic Activity on VIM- and NDM-1-Producing Clinical Isolates.

Metallo-β-lactamases (MBLs) contribute to the resistance of Gram-negative bacteria to carbapenems, last-resort antibiotics at hospital, and MBL inhibitors are urgently needed to preserve these important antibacterial drugs. Here, we describe a series of 1,2,4-triazole-3-thione-based inhibitors displaying an α-amino acid substituent, which amine was mono- or disubstituted by (hetero)aryl groups. Compounds disubstituted by certain nitrogen-containing heterocycles showed submicromolar activities against VIM-type enzymes and strong NDM-1 inhibition ( = 10-30 nM).

1,2,4-Triazole-3-thione analogues with an arylakyl group at position 4 as metallo-β-lactamase inhibitors.

Metallo-β-lactamases (MBLs) represent an increasingly serious threat to public health because of their increased prevalence worldwide in relevant opportunistic Gram-negative pathogens. MBLs efficiently inactivate widely used and most valuable β-lactam antibiotics, such as oxyiminocephalosporins (ceftriaxone, ceftazidime) and the last-resort carbapenems. To date, no MBL inhibitor has been approved for therapeutic applications.

Persistence and Dissemination Capacities of a -Harboring IncX-3 Plasmid in Isolated from an Urban River in Montpellier, France.

To investigate the capacities of persistence and dissemination of within and in aquatic environment, we characterized (sequence type 636) strains B26 and B28 isolated one month apart from the same urban river in Montpellier, France. The two isolates carried a pTsB26 plasmid, which sized 45,495 Kb, harbored gene and belonged to IncX-3 incompatibility group. pTsB26 was conjugative in vitro at high frequency, it was highly stable after 400 generations and it exerted no fitness cost on its host.

1,2,4-Triazole-3-Thione Analogues with a 2-Ethylbenzoic Acid at Position 4 as VIM-type Metallo-β-Lactamase Inhibitors.

Metallo-β-lactamases (MBLs) are increasingly involved as a major mechanism of resistance to carbapenems in relevant opportunistic Gram-negative pathogens. Unfortunately, clinically efficient MBL inhibitors still represent an unmet medical need. We previously reported several series of compounds based on the 1,2,4-triazole-3-thione scaffold.

Monitoring Urban Beach Quality on a Summer Day: Determination of the Origin of Fecal Indicator Bacteria and Antimicrobial Resistance at Prophète Beach, Marseille (France).

A highly frequented beach in Marseille, France, was monitored on an hourly basis during a summer day in July 2018, to determine possible water and sand fecal pollution, in parallel with influx of beach users from 8 a.m. to 8 p.

[Facing pandemics from past to present].

An outbreak means a sudden rise of the incidence of a disease, generally infectious, at a certain place over an extended period of time. The term pandemic is used when an outbreak is spreading on a global scale. By the past, Human has been able to face several pandemics by developing preventive and therapeutic strategies.

The Hydric Environment: A Hub for Clinically Relevant Carbapenemase Encoding Genes.

Carbapenems are β-lactams antimicrobials presenting a broad activity spectrum and are considered as last-resort antibiotic. Since the 2000s, carbapenemase producing (CPE) have emerged and are been quickly globally spreading. The global dissemination of carbapenemase encoding genes (CEG) within clinical relevant bacteria is attributed in part to its location onto mobile genetic elements.

Tailoring the Physicochemical Properties of Antimicrobial Peptides onto a Thiazole-Based γ-Peptide Foldamer.

Antimicrobial peptides (AMPs) are amphipathic molecules displaying broad-spectrum bactericidal activity, providing opportunities to develop a new generation of antibiotics. However, their use is limited either by poor metabolic stability or by high hemolytic activity. We herein addressed the potential of thiazole-based γ-peptide oligomers named ATCs as tunable scaffolds to design polycationic AMP mimetics.

Antibiotic resistance in urban runoff.

Aquatic ecosystems subjected to anthropogenic pressures are places of rapid evolution of microbial communities and likely hotspots for selection and emergence of antibiotic resistant bacteria. In urban settings, water quality and the risk of infection are generally assessed in sewers and in effluents of wastewater treatment plants. Physical and chemical parameters as well as the presence of antibiotics, antibiotic-resistant bacteria and genes of resistance are driven by urban activities, with adverse effects on aquatic ecosystems.

Transmission of IMI-2 carbapenemase-producing Enterobacteriaceae from river water to human.

Objectives: Carbapenemase-producing Enterobacteriaceae (CPE) are increasing worldwide in human infections. The role of rivers as reservoirs is highlighted, but transmission from the environment to humans is not documented. A human case of bacteraemia caused by IMI-2 carbapenemase-producing Enterobacter asburiae following massive river water exposure underwent microbiological investigations with the aim of deciphering the origin and mechanism of infection.

Simple and Specific Grafting of Antibacterial Peptides on Silicone Catheters.

To fight against nosocomial infection initiated by colonization of medical devices, a strategy enabling the direct and fast functionalization of silicone surfaces is proposed. This strategy proceeds in a site-specific way using original hybrid silylated antibacterial peptides. This safe and up-scalable method guarantees a covalent and robust immobilization with the correct orientation of the bioactive moiety.