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Increasing antimicrobial resistance and the development of multi-drug resistant (MDR) Pseudomonas aeruginosa is dependent on the expression of efflux pumps. This study aimed to investigate the role of overexpression of MexCD-OprJ and MexEF-OprN efflux pumps in reduced susceptibility to antimicrobial agents among P. aeruginosa strains. Totally, 100 clinical isolates of P. aeruginosa were collected from patients and the strains were identified by standard diagnostic tests. The MDR isolates were detected using the disk agar diffusion method. The expression levels of MexCD-OprJ and MexEF-OprN efflux pumps were evaluated by the real-time PCR. Forty-one isolates showed MDR phenotype, while piperacillin-tazobactam and levofloxacin were the most- and least-effective antibiotics, respectively. Also, all 41 MDR isolates showed a more than tenfold increase in the expression of mexD and mexF genes. In this study, a significant relationship was observed between the rate of antibiotic resistance, the emergence of MDR strains, and increasing the expression levels of MexEF-OprN and MexCD-OprJ efflux pumps (P < 0.05). Efflux systems mediated resistance was a noteworthy mechanism causative to multidrug resistance in P. aeruginosa clinical isolates. The study results demonstrated mexE and mexF overexpression as the primary mechanism conferring in the emergence of MDR phenotypes among P. aeruginosa strains. In addition, we also show that piperacillin/tazobactam exhibited a stronger ability in the management of infections caused by MDR P. aeruginosa in this area.
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http://dx.doi.org/10.1007/s00284-023-03330-z | DOI Listing |
J Biol Chem
September 2025
Research Unit in Biology of Microorganisms (URBM), Department of Biology, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium.
Metals like copper (Cu), zinc, and nickel exhibit dual nature, necessitating a tight regulation of their cellular homeostasis to meet physiological demands while preventing toxicity. In bacteria, metal homeostasis involves inner membrane (IM) P-type ATPases and ABC transporters, envelope-spanning tripartite efflux pumps, and outer membrane (OM) pore-forming proteins. Four decades ago, the OM β-barrel protein PcoB was shown to provide an additional layer of Cu resistance in an Escherichia coli strain isolated from the gut of swine fed with Cu supplements.
View Article and Find Full Text PDFBiochemistry
September 2025
Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
The recent discovery that the model multidrug efflux pump from , EmrE, can perform multiple types of transport suggests that this may be a compelling target for therapeutic intervention. Initial studies have identified several small-molecule substrates capable of inducing transporter-dependent susceptibility rather than the well-known antibiotic resistance phenotype. However, many questions regarding the underlying mechanism and regulation of this transporter still remain.
View Article and Find Full Text PDFInfect Drug Resist
August 2025
School of Medicine, Huzhou University, Huzhou, 313000, China.
Background: Milk powder is a key food source, especially for infants and vulnerable groups. However, Bacillus contamination during production, storage, or handling can cause spoilage, quality issues, or health risks. This study identified and isolated from commercially available Chinese milk powder.
View Article and Find Full Text PDFFront Cell Infect Microbiol
September 2025
Department of Respiratory Diseases, The Eighth Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
Objective: To identify genes related to eravacycline resistance in () and to provide a theoretical basis for the study of eravacycline resistance mechanisms in and the development of new antibiotics.
Methods: The study employed an integrated omics approach: (1) antimicrobial susceptibility profiling via broth microdilution to determine baseline MICs for eravacycline and comparator drugs; (2) Induction of resistance in clinical isolates (WJ_4, WJ_14, WJ_18) with low eravacycline MICs through serial passage in escalating drug concentrations; (3) Transcriptome sequencing (RNA-seq) and whole-genome sequencing (WGS) of -induced resistant strains (WJ_4a, WJ_14a, WJ_18a) and a clinical high-MIC isolate (WJ_97); (4) Bioinformatics analyses, including differential gene expression screening (with |log2(fold change)| > 2 and FDR-adjusted p < 0.05), SNP detection via GATK, and copy number variation (CNV) quantification using CCNE-acc to identify and compare resistance-related genetic alterations.
Antibiotic resistance is among the greatest threats of the modern era. Multidrug efflux pumps expel antibiotics from bacterial cells and present a particular challenge by conferring resistance to a broad range of antibiotic classes; however, there is currently a lack of potent and selective inhibitors. Here, we report the discovery of , a drug-like chemical probe for the multidrug efflux pump NorA that delivers low-nanomolar potentiation of ciprofloxacin activity and activity in an infection model.
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