CHEMICAL ENGINEERING JOURNAL
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2022
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IF 16.744
Shuang Tian,Linzhu Su,Yingli An,Henny C. van der Mei,Yijin Ren,Henk J. Busscher,Linqi Shi
DNase can break down the extracellular matrix that keeps infectious bacterial biofilm together through cleavage of eDNA. Herewith, biofilm bacteria can become dispersed to assist antibiotic eradication but this has hitherto remained an in vitro possibility. In vivo DNase is rapidly broken down in blood, impeding blood-injection of DNase combined with antibiotics to cure bacterial infections. Herein, we report the synthesis of pH-responsive, self-targeting micelles self-assembled from a solution of poly(ethylene glycol)- block -poly(ε-caprolactone) (PEG- b -PCL) and poly(ε-caprolactone)- block -poly(amino ester) (PCL- b -PAE) with DNase conjugated to PAE-blocks. At physiological pH, this conjugation protected DNase inside the micellar shell, while PEG prevented adsorption of blood-borne proteins to the micelles. PAE became positively-charged below pH 6.4 facilitating self-targeting to an infectious biofilm. Simultaneously, PAE became hydrophilic and stretched to expose DNase upon accumulation in an infectious S. aureus biofilm where it degraded the biofilm matrix. PEG/PAE-DNase micelles internally core-loaded with ciprofloxacin significantly better eradicated murine pneumonia after blood-injection than ciprofloxacin-loaded PEG/PAE micelles without conjugated DNase or ciprofloxacin free in solution. Considering that DNase is clinically approved for use in cystic fibrosis patients, this paves the way for clinical translation of ciprofloxacin-loaded, PEG/PAE-DNase micelles for the treatment of pneumonia and other infections that can be reached through self-targeting after blood-injection.
研究领域:
药学
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生物医学工程
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微生物学
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药物递送系统
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DOI
高影响因子
Annals of Clinical Microbiology and Antimicrobials
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2025
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IF 3.6
Ai Guo,Dianbao Zuo,Li Shi,Ming Guo,Jinquan Li,Caili Li,Puqing Wang,Xiaodong Sun,Ming Sang
Background The emergence of MDR K. pneumoniae poses a critical challenge in treating respiratory-associated pneumonia. Bacteriophages are promising antibiotic alternatives with unique features. This study aimed to isolate new bacteriophages from the hospital environment and investigate their therapeutic potential and mechanisms. Methods We employed plaque assays, transmission electron microscopy, and whole-genome sequencing to systematically characterize the biological properties, morphology, and genomic profiles of the phages in parallel. The bacteriostatic curve, biofilm staining quantification, and biofilm inhibition rate assay were employed to evaluate the in vitro lytic efficacy of the phage. More importantly, we established the murine pneumonia infection models through nasal instillation, assessed the therapeutic potential of the phage in vivo by observing pathological morphology via HE staining, detecting pro-inflammatory cytokine levels via qPCR and ELISA, and monitoring bacterial load changes in lung tissue through PCR analysis. Results Phages vB_KpnP_XY3 and vB_KpnP_XY4, taxonomically classified as Siphoviridae , demonstrated broad temperature (4–60 °C), pH (4–11) tolerance, chloroform resistance, latent periods of 40/35 min, and burst sizes of 340/126 PFU/cell. Both genomes contained circular dsDNA genomes (47,466 bp/50,036 bp) without virulence or antibiotic resistance genes. The bacterial concentration markedly decreased at 2 h post-treatment, reaching its biological nadir by 6 h. Concurrent biofilm assays demonstrated 80% biofilm inhibition and rapid bacterial clearance. In murine pneumonia models, both phage monotherapy and phage-antibiotic combinations significantly reduced bacterial loads compared with antibiotics alone ( P < 0.05), concurrently attenuating inflammation (IL-1β/IL-6/TNF-a. P < 0.0001) and restoring alveolar architecture with reduced necrosis. Conclusion The phages vB_KpnP_XY3 and vB_KpnP_XY4 demonstrated robust environmental adaptability. Its antibacterial effect is related to its specific biofilm dissolution performance in vivo and in vitro. These findings provide strong evidence for the precise phage treatment of MDR K. pneumoniae infections. Supplementary Information The online version contains supplementary material available at 10.1186/s12941-025-00812-9.
研究领域:
微生物学
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病毒学
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传染病学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
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2025
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IF 9.1
Lijuan Huang,Bing Du,Xiaohu Cui,Meiqi Liu,Zhoufei Li,Xiaoyun Cui,Ziying Xu,Zihui Yu,Shuo Zhao,Yanling Feng,Hanqing Zhao,Jianhai Long,Jing Yuan
Klebsiella pneumoniae (Kpn) is a common opportunistic pathogen, with hypervirulent strains (hvKpn) posing significant risks even to healthy individuals. Traditional clinical diagnostics often use real-time quantitative polymerase chain reaction (PCR) with TaqMan probes, which are costly and unstable due to their reliance on fluorophore and quencher molecules. This study introduces a novel probe using silicon-doped carbon quantum dots (Si-QDs) and single-layer graphene oxides (GOs), forming the Si-QD-probe-GO. This new probe offers excellent selectivity, sensitivity, stability, low photobleaching, and cost-effectiveness. A sensor array targeting khe, peg-344, and iucA genes is developed to detect Kpn and differentiate between classical Kpn (cKpn) and hvKpn. Using a partial least-squares discriminant analysis (PLS-DA) model, the system achieves 100% accuracy in distinguishing hvKpn from cKpn. The study also employs droplet digital PCR (ddPCR) with microfluidic technology to enhance sensitivity and quantification, achieving a detection limit of 5 CFU/mL. In a mouse pneumonia model, the PLS-DA model accurately identifies hvKpn in lung samples. The ddPCR quantification using Si-QD-probe-GO shows strong correlation with traditional culture methods. This research presents a promising ddPCR system for precise detection and virulence identification of Kpn, offering a new direction for clinical diagnostics.
研究领域:
微生物学
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分子诊断
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纳米技术
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生物医学工程
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传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
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2024
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IF 3.9
Yujia Chen,Wei Li,Li Wang,Bingmei Wang,Jian Suo
In confronting the significant challenge posed by multidrug-resistant (MDR) pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), the development of innovative anti-infective strategies is essential. Our research focuses on sortase A (SrtA), a vital enzyme for anchoring surface proteins in S. aureus. We discovered that plantamajoside (PMS), a phenylpropanoid glycoside extracted from Plantago asiatica L. (Plantaginaceae), acts as an effective and reversible inhibitor of SrtA, with a notable IC50 value of 22.93 µg/mL. This breakthrough provides a novel approach to combat both resistance and virulence in MRSA. PMS significantly inhibits S. aureus adhesion to fibrinogen, reducing biofilm formation and hindering the anchoring of staphylococcal protein A to the cell wall. Live-dead cell assays demonstrated increased survival rates in PMS-treated MRSA-infected A549 cells. Fluorescence quenching experiments revealed a robust interaction between PMS and SrtA, with mechanistic analyses pinpointing the critical R197 amino acid residue as the target site. In vivo, PMS was highly effective in a Galleria mellonella infection model, reducing mortality rates in MRSA-infected larvae. Additionally, PMS demonstrated therapeutic efficacy in a mouse pneumonia model, improved survival rates, reduced the bacterial load in pulmonary tissues, and mitigated lung damage. These results validate PMS as a promising compound to mitigate MRSA virulence and thwart resistance by targeting SrtA. This study highlights PMS as a leading candidate for controlling MRSA infections, showing the potential of targeting specific bacterial mechanisms in the fight against MDR infections.
研究领域:
微生物学
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药理学
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传染病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2021
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IF 9.776
Xingyue Yang,Qian Qiu,Gengqi Liu,He Ren,Xiaojie Wang,Jonathan F. Lovell,Yumiao Zhang
Effective delivery of antimicrobial agents to intracellular pathogens represents a major bottleneck for a wide variety of infectious diseases. To address this, we developed SIR-micelles(+), as a new delivery vehicle comprising antibiotic-loaded micelles with rapid self-immolation within cells for targeted delivery to macrophages, where most intracellular bacterial reside. After phagocytosis, SIR-micelles(+) rapidly release the pristine antibiotic after the cleavage of the disulfide bonds by intracellular reducing agents such as glutathione (GSH). Colistin , a hydrophilic and potent “last-resort” antibiotic used for the treatment of drug-resistant bacterial infection, was encapsulated in SIR-micelles with 40% yield and good short-term storage stability. Hydrophobic moieties and mannose ligands in SIR-micelles(+) enhanced the delivery of colistin into macrophages. The traceless and thiol-responsive release of colistin effectively eliminated intracellular Escherichia coli within twenty minutes. In a murine pneumonia model, SIR-micelles(+) significantly reduced bacterial lung burden of multidrug-resistant Klebsiella pneumoniae . Furthermore, SIR-micelles(+) improved the survival rate and reduced the bacterial burden of organs infected by intracellular bacteria transferred from donor mice. Using this formulation approach, the nephrotoxicity and neurotoxicity induced by antibiotic were reduced by about 5– 15 fold. Thus, SIR-micelles(+) represent a new class of material that can be used for targeting treatment of intracellular and drug-resistant pathogens.
研究领域:
药学
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感染性疾病
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纳米技术
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
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