Nanoscale
·
2020
·Vol. 12
·期 26
·13948-13957
·
IF 6.895
Wenzhen Liu,Yuxiang Zhang,Wenwu You,Jianqiang Su,Shaohua Yu,Tao Dai,Yunmei Huang,Xueyuan Chen,Xiaorong Song,Zhuo Chen
Extensively drug-resistant Acinetobacter baumannii (XDR-AB) has raised considerable concerns due to its mortal damage to humans and its high transmission rate of infections in hospitals. However, current antibiotics not only show poor anti-infection effects in vivo but also frequently cause high nephrotoxicity and neurotoxicity. Herein, we report a near-infrared (NIR) light-initiated antimicrobial photodynamic therapy (aPDT) to effectively treat in vivo XDR-AB infections based on photosensitizer (PS) loaded upconversion nanoparticles (UCNPs, LiYF4:Yb/Er). Such nanoagents feature robust NIR triggered UC luminescence and high-efficiency energy transfer from UCNPs to the loaded PS, thereby allowing NIR-triggered generation of reactive oxygen species (ROS) for destroying the bacterial cell membrane. This strategy permits a high antibacterial activity against XDR-AB, resulting in a decline of 4.72 log10 in viability at a dose of 50 μg mL−1 UCNPs-PVP-RB with 980 nm laser irradiation (1 W cm−2). More significantly, we can achieve excellent therapeutic efficacy against deep-tissue (about 5 mm) XDR-AB infections without causing any side effects in the murine model. In brief, such NIR-activated aPDT may open up new avenues for treating various deep-tissue intractable infections.
研究领域:
纳米技术
·
光动力疗法
·
抗菌剂
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF MICROBIOLOGY
·
2021
·Vol. 204
·期 1
·1-16
·
IF 2.552
Haris Muhammad,Chen Changming,Wu Jing,Ramzan Muhammad Noman,Taj Ayaz,Sha Shanshan,Ullah Hayan,Ma Yufang
Tuberculosis (TB) causes millions of deaths each year across the globe. Multiple drug-resistant (MDR) and extensively drug-resistant (XDR) mycobacterial strains have made the treatment extremely difficult. To overcome this hurdle, the development of new drug targets and an effective treatment strategy are desperately needed. This can be achieved by deciphering the role of essential genes and enzymes which are involved in cell survival. One such enzyme is glyoxalase II. The glyoxalase system (glyoxalase I and glyoxalase II) has a pivotal role in cellular survival and detoxification by converting methylglyoxal (MG) into lactate. Otherwise, the increased concentration of MG then modifies DNA, proteins, and lipids, resulting in abnormalities and cell death. Interestingly, the function and physiological role of glyoxalase II have remained undetermined in mycobacteria. In this study, the functional activity of MSMEG_2975 (putative glyoxalase II) after heterologous cloning and expression was determined. And the knockdown strain Mycobacterium smegmatis KD for MSMEG_2975 was constructed with tetracycline-inducible vector pMIND. The inducible knockdown of MSMEG_2975 affected bacterial growth, biofilm formation, transcriptome, and enhanced the susceptibility to antibiotics. This work represents mycobacterial glyoxalase II as a potential drug target against mycobacterial pathogens and indicates the crucial regulatory role of glyoxalase II in mycobacteria.
研究领域:
微生物学
·
分子生物学
·
药理学
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Jianling Huang,Xiuwen Hong,Sixi Chen,Yucong He,Lixu Xie,Fenglin Gao,Chenghua Zhu,Xiao Jin,Haihao Yan,Yongxia Ye,Mingyue Shao,Xingran Du,Ganzhu Feng
Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC-MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic-nano-antimicrobial therapy against gram-negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI 29-41 ) modified hUC-MSCs membrane (MSCm), a sonosensitizer meso-tetra(4-car-boxyphenyl) porphine doped mesoporous organo-silica nanoparticle and an acidity-responsive metal–organic framework ZIF-8. This innovative formulation enables efficient loading of polymyxin B, reduces off-target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli . Taking advantage of the bacterial targeting ability of UBI 29-41 and the inflammatory chemotaxis of hUC-MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M 2 phenotype, and improves survival rates without introducing adverse events. Overall, this study offers promising strategies for treating deep-tissue XDR bacterial infections, and guides the design and optimization of biomimetic nanomedicine.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
传染病学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）