c-di-GMP (3′-5′-cyclic diguanylic acid) inhibits Staphylococcus aureus cell-cell interactions and biofilm formation

被引:125
作者
Karaolis, DKR [1 ]
Rashid, MH
Chythanya, R
Luo, WS
Hyodo, M
Hayakawa, Y
机构
[1] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA
[3] Nagoya Univ, Grad Sch Informat Sci Human Informat, Nagoya, Aichi, Japan
[4] Nagoya Univ, CREST, JST, Nagoya, Aichi, Japan
关键词
D O I
10.1128/AAC.49.3.1029-1038.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Staphylococcus aureus is an important pathogen of humans and animals, and antibiotic resistance is a public health concern. Biofilm formation is essential in virulence and pathogenesis, and the ability to resist antibiotic treatment results in difficult-to-treat and persistent infections. As such, novel antimicrobial approaches are of great interest to the scientific, medical, and agriculture communities. We recently proposed that modulating levels of the cyclic dinucleotide signaling molecule, c-di-GMP (cyclic diguanylate [3',5'-cyclic diguanylic acid], cGpGp), has utility in regulating phenotypes of prokaryotes. We report that extracellular c-di-GMP shows activity against human clinical and bovine intramammary mastitis isolates of S. aureus, including methicillin-resistant S. aureus (MRSA) isolates. We show that chemically synthesized c-di-GMP is soluble and stable in water and physiological saline and stable following boiling and exposure to acid and alkali. Treatment of S. aureus with extracellular c-di-GMP inhibited cell-to-cell (intercellular) adhesive interactions in liquid medium and reduced (>50%) biofilm formation in human and bovine isolates compared to untreated controls. c-di-GMP inhibited the adherence of S. aureus to human epithelial HeLa cells. The cyclic nucleotide analogs cyclic GMP and cyclic AMP had a lesser inhibitory effect on biofilms, while 5'-GMP had no major effect. We propose that cyclic dinucleotides such as c-di-GMP, used either alone or in combination with other antimicrobial agents, represent a novel and attractive approach in the development of intervention strategies for the prevention of biofilms and the control and treatment of infection.
引用
收藏
页码:1029 / 1038
页数:10
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