Objectives: The NorA efflux pump in Staphylococcus aureus mediates resistance to many fluoroquinolone (FQ) antibiotics. Three norA alleles with high sequence similarity are found in various S. aureus strains exhibiting different FQ resistance profiles. This study aimed to elucidate the underlying molecular basis for the varying efflux activity of these three allelic variations.
Methods: The norA genotypes of 20 S. aureus isolates were analysed. Multiple alignments and conservative analyses were conducted to explore the evolutionary variations. After heterologous expression in Escherichia coli, seven mutants were constructed for MIC tests, efflux activity and conformational change measurements.
Results: Three NorA alleles were identified that displayed different FQ MICs and varying efflux activity for ethidium bromide, with the NorAII protein showing the strongest activity. A total of 29 single amino acid polymorphisms were identified by conservative analysis within three allelic peptides, with seven sites densely distributed in the 277-297 region. Mutations of these seven residues in NorAII all significantly impaired drug resistance and efflux activity, and three key mutants showed conformational changes in fluorescence resonance energy transfer (FRET) analysis.
Conclusions: Evolutionary variations of the 277-297 region could be a major explanation for the functional difference of three norA alleles and serve as a potential target for the development of novel NorA inhibitors.
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http://dx.doi.org/10.1093/jac/dkab066 | DOI Listing |
Arch Microbiol
January 2025
Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Jalan, UMS, 88400, Kota Kinabalu, Sabah, Malaysia.
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View Article and Find Full Text PDFVet Med Sci
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Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
A major risk to the poultry industry is antimicrobial resistance (AMR), specifically with regard to Mycoplasma gallisepticum (MG) infections. The sensitivity patterns of 100 MG isolates to biocides and antibiotics were examined in this study to clarify the interactions between antimicrobial agents and resistance mechanisms. The antimicrobial activity against MG was assessed using broth microdilution, and the results are shown as the minimum inhibitory concentration (MIC) for each strain, the MIC distribution (range), the MIC, and/or the MIC.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:
Cynanchum wallichii (CW) is a traditional Chinese medicine which is widely used for treating arthrophlogosis, traumatic injury, and other conditions. Herein, we investigate the effects and mechanisms of CW and its bioactive constituent CW1 in reversing docetaxel (DTX) resistance in prostate cancer (PCa) cells. We investigated the reversal effects of CW and its bioactive constituent CW1 on 22Rv1/DTX cells in vitro and in vivo.
View Article and Find Full Text PDFWater Res
January 2025
School of Civil and Environmental Engineering, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address:
Chlorine, the most widely utilized disinfectant for drinking water globally, has recently been implicated in facilitating the spread of antibiotic resistance genes (ARGs), raising concerns about its underestimated environmental and ecological risks. However, given the current fragmented research focus and results, a comprehensive understanding of the potential mechanisms and influencing factors behind chlorination-promoted ARGs transmission in drinking water systems is crucial. This work is the first to systematically review the variations in abundance, transmission mechanisms, influencing factors, and mitigation strategies related to ARGs during the chlorination process.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Shaanxi Normal University, Xi'an 710119, P. R. China.
High expression of drug efflux pump makes antibiotics ineffective against bacteria, leading to drug-resistant strains and even the emergence of "superbugs". Herein, we design and synthesize a dual functional o-nitrobenzene (NB)-modified conjugated oligo-polyfluorene vinylene (OPFV) photosensitizer, OPFV-NB, which can depress efflux pump activity and also possesses photodynamic therapy (PDT) for synergistically overcoming drug-resistant bacteria. Upon light irradiation, the OPFV-NB can produce aldehyde active groups to covalently bind outer membrane proteins, such as tolerant colicin (TolC), blocking drug efflux of bacteria.
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