The global rate of Amphotericin B (AmB) resistance in Candida auris has surpassed 12%. However, there is limited data on available clinical treatments and microevolutionary analyses concerning reduced AmB sensitivity. In this study, we collected 18 C. auris isolates from five patients between 2019 and 2022. We employed clinical data mining, genomic, and transcriptomic analyses to identify genetic evolutionary features linked to reduced AmB sensitivity in these isolates during clinical treatment. We identified six isolates with a minimum inhibitory concentration (MIC) of AmB below 0.5 µg/mL (AmB^0.5) and 12 isolates with an AmB-MIC of 1 µg/mL (AmB¹) or ≥ 2 µg/mL (AmB²). All five patients received 24-hour AmB (5 mg/L) bladder irrigation treatment. Evolutionary analyses revealed an ERG3 (c923t) mutation in AmB¹ C. auris. Additionally, AmB² C. auris was found to contain a t2831c mutation in the RAD2 gene. In the AmB¹ group, membrane lipid-related gene expression (ERG1, ERG2, ERG13, and ERG24) was upregulated, while in the AmB² group, expression of DNA-related genes (e.g. DNA2 and PRI1) was up-regulated. In a series of C.auris strains with reduced susceptibility to AmB, five key genes were identified: two upregulated (IFF9 and PGA6) and three downregulated (HGT7, HGT13,and PRI32). In this study, we demonstrate the microevolution of reduced AmB sensitivity in vivo and further elucidate the relationship between reduced AmB sensitivity and low-concentration AmB bladder irrigation. These findings offer new insights into potential antifungal drug targets and clinical markers for the "super fungus", C. auris.

2024-12-01·Biotechnology Letters

High-yield magnetosome production of Magnetospirillum magneticum strain AMB-1 in flask fermentation through simplified processing and optimized iron supplementation

Article

作者: Huang, Yandi ; Qin, Song ; Liu, Zhengyi ; Wang, Yu ; Li, Wenjun ; Cui, Hongli

OBJECTIVESDeveloping a simplified flask fermentation strategy utilizing magnetotactic bacterium AMB-1 and optimized iron supplementation for high-yield magnetosome production to address the challenges associated with magnetosome acquisition.RESULTSA reliable processing for the pure culture of AMB-1 was established using standard laboratory consumables and equipment. Subsequently, the medium and iron supplementation were optimized to enhance the yield of AMB-1 magnetosomes. The mSLM supported higher biomass accumulation in flask fermentation, reaching an OD₅₆₅ of ~ 0.7. The premixed solution of ferric quinate and EDTA-Fe (at a ratio of 0.5:0.5 and a concentration of 0.4 mmol/L) stabilized Fe³⁺ and significantly increased the reductase activity of AMB-1. Flask fermentations with an initial volume of 15 L were then conducted employing the optimized fermentation strategy. After two rounds of iron and nutrient supplementation, the magnetosome yield reached 185.7 ± 9.5 mg/batch (approximately 12 mg/L), representing the highest AMB-1 flask fermentation yield to our knowledge.CONCLUSIONA flask fermentation strategy for high-yield magnetsome production was developed, eliminating the need for bioreactors and greatly simplifying the process of magnetosome acquisition.

2024-05-28·ACS Omega

Magnetotactic Bacteria AMB-1 with Active Deep Tumor Penetrability for NIR-II Photothermal Tumor Therapy

Article

作者: Chen, Lihong ; Sun, Yutong ; Zhu, Guifen ; Chen, Liqun ; Chen, Wenwen ; Chen, Rong ; Lin, Ruipeng ; Huang, Guoming ; Hong, Dengke

The complex tumor structure and microenvironment such as abnormal tumor vasculature, dense tumor matrix, and elevated interstitial fluid pressure greatly hinder the penetration and retention of therapeutic agents in solid tumors. The development of an advanced method for robust penetration and retention of therapeutic agents in tumors is of great significance for efficient tumor treatments. In this work, we demonstrated that magnetotactic bacteria AMB-1 with hypoxic metabolism characteristics can actively penetrate the tumor to selectively colonize deep hypoxic regions, which emerge as a promising intelligent drug carrier. Furthermore, AMB-1 presents intrinsic second near-infrared (NIR-II) photothermal performance that can efficiently convert a 1064 nm laser into heat for tumor thermal ablation. We believe that our investigations not only develop a novel bacteria-based photothermal agent but also provide useful insights for the development of advanced tumor microbial therapies.

100 项与 AMB-001 相关的药物交易

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