Overcoming (X)-harboring tigecycline resistance: a study on the efficacy of tigecycline-apramycin combinations.

Introduction: The emergence of the wide variety of novel tigecycline resistance (X) variants, including (X3), (X4), (X5), and (X6), has raised a serious threat to global public health and posed a significant challenge to the clinical treatment of multidrug-resistant bacterial infections.

Methods: In this study, we evaluated the synergism of tigecycline combining with other antibiotics as a means of overcoming the (X)-mediated resistance in spp. Antibiotic synergistic efficacy was evaluated through chequerboard experiments, time-kill assays and dose-response curves.

Rutin Synergizes with Colistin to Eradicate Salmonellosis in Mice by Enhancing the Efficacy and Reducing the Toxicity.

The wide dissemination of multidrug-resistant (MDR) Gram-negative bacteria poses a significant global health and security concern. As developing new antibiotics is generally costly, fastidious, and time-consuming, there is an urgent need for alternative therapeutic strategies to address the gap in antibiotic discovery void. This study aimed to investigate the activity of colistin (CS) in combination with a natural product, rutin (RT), to combat against Typhimurium ( Tm) in vitro and in vivo.

Assessment of anti-MRSA activity of auranofin and florfenicol combination: a PK/PD analysis.

Aims: Methicillin-resistant Staphylococcus aureus (MRSA) is an important zoonotic pathogen with multidrug-resistant phenotypes increasingly prevalent in both human and veterinary clinics. This study evaluated the potential of auranofin (AF) as an antibiotic adjuvant to enhance the anti-MRSA activity of florfenicol (FFC) and established a pharmacokinetic/pharmacodynamic (PK/PD) model to compare the efficacy of FFC alone or in combination with AF against MRSA.

Methods And Results: We observed an increased susceptibility and significant synergistic effects of MRSA to FFC in the presence of AF.

Metabolic disruption exacerbates intestinal damage during sleep deprivation by abolishing HIF1α-mediated repair.

Sleep deprivation (SD) has been reported to induce intestinal damage by several mechanisms, yet its role in modulating epithelial repair remains unclear. In this study, we find that chronic SD leads to colonic damage through continuous hypoxia. However, HIF1α, which generally responds to hypoxia to modulate barrier integrity, was paradoxically dysregulated in the colon.

Evolution and maintenance of a large multidrug-resistant plasmid in a Typhimurium host under differing antibiotic selection pressures.

The dissemination of antibiotic resistance genes (ARGs) through plasmids is a major mechanism for the development of bacterial antimicrobial resistance. The adaptation and evolution mechanisms of multidrug-resistant (MDR) plasmids with their hosts are not fully understood. Herein, we conducted experimental evolution of a 244 kb MDR plasmid (pJXP9) under various conditions including no antibiotics and mono- or combinational drug treatments of colistin (CS), cefotaxime (CTX), and ciprofloxacin (CIP).

Metagenomic analysis unveiled the response of microbial community and antimicrobial resistome in natural water body to duck farm sewage.

Sewages from duck farms are often recognized as a major source of antimicrobial resistance and pathogenic bacteria discharged to natural water bodies, but few studies depicted the dynamic changes in resistome and microbial communities in the rivers under immense exposure of sewage discharge. In this study, we investigated the ecological and environmental risks of duck sewages to the rivers that geographically near to the duck farms with short-distance (<1 km) using 16S rRNA amplicon and metagenomic sequencing. The results showed that a total of 20 ARG types were identified with abundances ranged from 0.

Cinnamaldehyde targets SarA to enhance β-lactam antibiotic activity against methicillin-resistant .

Methicillin-resistant (MRSA) is a current global public health problem due to its increasing resistance to the most recent antibiotic therapies. One critical approach is to develop ways to revitalize existing antibiotics. Here, we show that the phytogenic compound cinnamaldehyde (CIN) and β-lactam antibiotic combinations can functionally synergize and resensitize clinical MRSA isolates to β-lactam therapy and inhibit MRSA biofilm formation.

Concentration-resistance relationship and PK/PD evaluation of danofloxacin against emergence of resistant Pasteurella multocida in an in vitro dynamic model.

Aims: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis.

Methods And Results: Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model.

Daily occupational exposure in swine farm alters human skin microbiota and antibiotic resistome.

Antimicrobial resistance (AMR) is a major threat to global public health, and antibiotic resistance genes (ARGs) are widely distributed across humans, animals, and environment. Farming environments are emerging as a key research area for ARGs and antibiotic resistant bacteria (ARB). While the skin is an important reservoir of ARGs and ARB, transmission mechanisms between farming environments and human skin remain unclear.

Innovative Delivery System Combining CRISPR-Cas12f for Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Antimicrobial resistance poses a significant global challenge, demanding innovative approaches, such as the CRISPR-Cas-mediated resistance plasmid or gene-curing system, to effectively combat this urgent crisis. To enable successful curing of antimicrobial genes or plasmids through CRISPR-Cas technology, the development of an efficient broad-host-range delivery system is paramount. In this study, we have successfully designed and constructed a novel functional gene delivery plasmid, pQ-mini, utilizing the backbone of a broad-host-range Inc.

Tobramycin-resistant small colony variant mutant of serovar Typhimurium shows collateral sensitivity to nitrofurantoin.

The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the gene, which render .

Antimicrobial resistance and population genomics of emerging multidrug-resistant 4,[5],12:i:- in Guangdong, China.

4,[5],12:i:-, a monophasic variant of Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of 4,[5],12:i:- across Guangdong. 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages.

Pharmacokinetic/pharmacodynamic evaluation of gamithromycin against rabbit pasteurellosis.

Background: Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we sought to determine the pharmacokinetic profiles, antimicrobial activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with therapeutic effect of gamithromycin against Pasteurella multocida in rabbits.

Results: Gamithromycin showed favorable PK properties in rabbits, including high subcutaneous bioavailability (86.

Targeted inhibition of gut bacterial β-glucuronidases by octyl gallate alleviates mycophenolate mofetil-induced gastrointestinal toxicity.

Mycophenolate mofetil (MMF) is a viable therapeutic option against various immune disorders as a chemotherapeutic agent. Nevertheless, its application has been undermined by the gastrotoxic metabolites (mycophenolic acid glucuronide, MPAG) produced by microbiome-associated β-glucuronidase (βGUS). Therefore, controlling microbiota-produced βGUS underlines the potential strategy to improve MMF efficacy by overcoming the dosage limitation.

Molecular characteristic of mcr-1 gene in Escherichia coli from aquatic products in Guangdong, China.

Objectives: Aquatic ecosystems serve as a dissemination pathway and a reservoir of both antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). This study aimed to determine the prevalence of colistin-resistant mcr-like genes in Enterobacteriales in aquatic products, which may be contribute to the transfer of ARGs in water environments.

Methods: The mcr-1-positive Escherichia coli were recovered from 123 freshwater fish and 34 cultured crocodile cecum samples from 10 farmers' markets in Guangdong, China.

Increased Activity of β-Lactam Antibiotics in Combination with Carvacrol against MRSA Bacteremia and Catheter-Associated Biofilm Infections.

β-Lactam antibiotics are the mainstay for the treatment of staphylococcal infections, but their utility is greatly limited by the emergence and rapid dissemination of methicillin-resistant (MRSA). Herein, we evaluated the ability of the plant-derived monoterpene carvacrol to act as an antibiotic adjuvant, revitalizing the anti-MRSA activity of β-lactam antibiotics. Increased susceptibility of MRSA to β-lactam antibiotics and significant synergistic activities were observed with carvacrol-based combinations.

Dynamic human exposure to airborne bacteria-associated antibiotic resistomes revealed by longitudinal personal monitoring data.

Airborne antibiotic-resistant bacteria (ARB) can critically impact human health. We performed resistome profiling of 283 personal airborne exposure samples from 15 participants spanning 890 days and 66 locations. We found a greater diversity and abundance of airborne bacteria community and antibiotic resistomes in spring than in winter, and temperature contributed largely to the difference.