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Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI. Cite this article: 2022;104-B(5):575-580.
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http://dx.doi.org/10.1302/0301-620X.104B5.BJJ-2021-1759.R1 | DOI Listing |
Org Lett
September 2025
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
Halogenated phenazines hold promise as antimicrobial and antibiofilm agents, yet are mainly accessed via chemical synthesis. Herein, we report PezW, a novel single-component flavin-dependent halogenase (FDH) that halogenates phenazine scaffolds, notably enabling enzymatic synthesis of bioactive 2-bromo-1-hydroxyphenazine () and 2,4-bromo-1-hydroxyphenazine (). Structural modeling and mutagenesis revealed key residues critical for substrate binding and catalysis.
View Article and Find Full Text PDFTrends Pharmacol Sci
September 2025
Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, Innsbruck, Austria.
The escalating threat of antimicrobial resistance demands innovative therapeutic strategies beyond classical targets. Recent insights into the mechanisms of bacterial iron acquisition - ranging from siderophores and heme uptake to ferrous iron transport - have enabled new approaches to impair pathogen growth and virulence. These pathways are increasingly being harnessed for therapeutic gain.
View Article and Find Full Text PDFFish Shellfish Immunol
September 2025
Laboratory of Applied Immunology in Aquaculture, Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, 88035-972 Florianópolis, SC, Brazil. Electronic address:
Environmental and nutritional factors are critical in modulating the immune system of Penaeus vannamei, particularly under viral threats such as white spot syndrome virus (WSSV). This study evaluated the effects of two Amazonian plant-based feed additives, buriti (Mauritia flexuosa) and pracaxi (Pentaclethra macroloba) brans, on shrimp immunocompetence, oxidative balance, and resistance to WSSV. Shrimp were fed diets supplemented with 4% or 8% of each ingredient.
View Article and Find Full Text PDFToxicol Appl Pharmacol
September 2025
Department of Pharmacological & Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX 77204, United States; Department of Pharmacy Practice & Translational Research, University of Houston College of Pharmacy, Houston, TX 77204, United States. Electronic address:
Vancomycin is one of the most commonly used parenteral antibiotics for treating drug-resistant bacterial infections, however, it is hindered by nephrotoxicity. We previously demonstrated that zileuton could delay the onset of vancomycin-associated nephrotoxicity in rats. Here, we sought to understand the mechanism(s) of zileuton renal protection.
View Article and Find Full Text PDFJ Control Release
September 2025
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China. Electronic address:
The tumor microenvironment (TME) is a complex and dynamic ecosystem that significantly influences tumor progression, immune modulation, and therapeutic response. A key component of the TME is the tumor-associated microbiota, which has emerged as an important player in cancer biology, affecting tumor metastasis, immune evasion, and resistance to treatments. The recent advent of high-throughput sequencing technologies has revolutionized our understanding of the microbiome, revealing distinct microbial communities across various tumor types.
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