Hyaluronic acid conjugation facilitates clearance of intracellular bacterial infections by streptomycin with neglectable nephrotoxicity

被引：18

作者：

Qiu, Yuanhao ^{[1
]}

Hou, Yilin ^{[1
]}

Sun, Feifei ^{[1
]}

Chen, Peng ^{[1
]}

Wang, Dongdong ^{[1
]}

Mu, Haibo ^{[1
]}

Zhang, Xiaoli ^{[1
]}

Ding, Kan ^{[2
]}

Duan, Jinyou ^{[1
]}

机构：

[1] Northwest A&F Univ, Coll Chem & Pharm, Shaanxi Key Lab Nat Prod & Chem Biol, Yangling 712100, Shaanxi, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China

来源：

GLYCOBIOLOGY | 2017年 / 27卷 / 09期

基金：

中国国家自然科学基金;

关键词：

CD44; hyaluronic acid; intracellular bacterial infections; streptomycin; N-DEACETYLATION; DRUG-DELIVERY; ANTIBIOTICS; EXPRESSION; AMINOGLYCOSIDES; NANOPARTICLES; CAPACITY; DISEASES; WATER;

D O I：

10.1093/glycob/cwx061

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Antibiotics such as beta-lactams and aminoglycosides are often subtherapeutic to intracellular infections due to their high hydrophilicity, resulting in low effectiveness against intracellular pathogens and the emergence of antibiotic resistance. Here we reported that an endogenous aminoglycan, hyaluronic acid could be an effective carbohydrate carrier of the aminoglycoside antibiotic, streptomycin against intracellular pathogens. This conjugation could enhance phagocytic activity, and facilitated the entry of streptomycin into host cells via a CD44-mediated pathway. It appeared that this conjugate could clear intracellular bacteria in phagocytic or nonphagocytic cells in a short-term therapy (4 h) at a lower effective dose. In addition, this conjugate was more efficient in reducing bacteria burden in an in vivo acute infection model than streptomycin did. Interestingly, subcutaneous injection of this conjugate at an excess amount had undetectable side effects such as nephrotoxicity. These results suggested that hyaluronic acid might be an efficient Trojan horse for the delivery of hydrophilic antibiotics to deal with intracellular infections.

引用

页码：861 / 867

页数：7

共 29 条

[1] PEGylation of the peptide Bac7(1-35) reduces renal clearance while retaining antibacterial activity and bacterial cell penetration capacity [J].