Nanorods overcome tigecycline resistance of Klebsiella pneumonia

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    Nanorods overcome tigecycline resistance of Klebsiella pneumonia
    Schematic depiction of the fabrication of the nanorods and the mechanism of overcoming the tigecycline resistance of TRKP. TIG: tigecycline; Ts-TPGS/Cap/TIG: tigecycline-loaded TPGS and S-thanatin functionalized calcium phosphate nanorods; TRKP: tigecycline-resistant Klebsiella pneumonia. LPS: lipopolysaccharide. Credit score: Zhejiang College College of Drugs

    Lengthy-term and extreme use of antibiotics has prompted the unfold of antibiotic resistance. The time- and cost-consuming course of of latest antibiotic growth ends in the a lot slower emergence of latest antibacterial medication than that of bacterial resistance. The emergence of superbugs has been rising to grow to be a dominant problem in human well being. Tigecycline is thought to be the final line of protection to fight multidrug-resistant Klebsiella pneumoniae. Nevertheless, growing utilization has led to rising drug resistance and remedy failure. Tigecycline resistance of Klebsiella pneumoniae stays a worldwide drawback that urgently must be solved.

    On June 29, 2022, Prof. Du Yongzhong from Faculty of Pharmaceutical Sciences, Zhejiang College, Prof. Lu Xiaoyang and Jiang Saiping from The First Affiliated Hospital, Zhejiang College College of Drugs co-published an article entitled “TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia” within the journal Nature Communications. Their analysis demonstrates that D-alpha tocopheryl polyethylene glycol succinate(TPGS)-modified and S-thanatin peptide (Ts)-functionalized nanorods based mostly on calcium phosphate nanoparticles can overcome tigecycline resistance of Klebsiella pneumonia.

    First, the researchers ready the tigecycline-loaded TPGS-modified and S-thanatin peptide-functionalized nanorods, Ts-TPGS/Cap/TIG (TTCT), and characterised the properties of TTCT. They discovered that the ready Ts-TPGS/Cap nanorods might successfully encapsulate TIG and obtain sustained drug launch. The TTCT with of ~25 nm wouldn’t disassemble in circulation and displayed wonderful stability at room temperature.

    Subsequent, the researchers evaluated the antibacterial exercise of TTCT and explored the underlying mechanisms of overcoming resistance. They discovered that Ts-TPGS/Cap exhibited concentrating on and enhanced accumulation in each Klebsiella pneumonia (KPN) and TRKP by way of the binding between Ts and LPS. TPGS might exert its inhibitory capability on the exercise of efflux pumps and the expression of acrA, acrB and ramA in TRKP. On this approach, the TIG focus inside micro organism was considerably larger within the TTCT group than different teams. The synergistic antibacterial capability between Ts and TIG additional enhanced the antibacterial exercise TTCT, thus overcoming the drug resistance of TRKP.

    In mice with pneumonia, Ts-TPGS/Cap particularly accrued within the lungs. TTCT administration might considerably scale back the and neutrophil counts in , and reduce the entire cell and C reactive protein (CRP) ranges in bronchoalveolar lavage fluid (BALF). Furthermore, TTCT was able to ameliorating neutrophil infiltration within the lungs and decreasing bacterial colonies from BALF, thus apparently growing the survival charges of mice with pneumonia brought on by TRKP.

    General, a TPGS-based and Ts-modified nanodrug supply system was designed. The ready nanorods can improve tigecycline accumulation in micro organism by way of the on efflux pumps exerted by TPGS and the concentrating on capability of S-thanatin to micro organism. The synergistic antibacterial capability between S-thanatin and tigecycline additional enhances the antibacterial exercise, thus overcoming the tigecycline resistance of TRKP. The findings present a therapeutic technique for infections illnesses brought on by MDR gram-negative micro organism.


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    Extra info:
    Xiaojuan Wang et al, TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia, Nature Communications (2022). DOI: 10.1038/s41467-022-31500-3

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    Zhejiang College College of Drugs

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    Nanorods overcome tigecycline resistance of Klebsiella pneumonia (2022, August 19)
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