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.
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Virginia Commonwealth Univ, Med Coll Virginia, Dept Med, Div Infect Dis, Richmond, VA 23298 USAVirginia Commonwealth Univ, Med Coll Virginia, Dept Med, Div Infect Dis, Richmond, VA 23298 USA
机构:
Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, IsraelTel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel
Balaban, N
Gov, Y
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机构:Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel
Gov, Y
Bitler, A
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机构:Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel
Bitler, A
Boelaert, JR
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机构:Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel
机构:
Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USAUniv Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA
Beenken, KE
Blevins, JS
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Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USAUniv Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA
Blevins, JS
Smeltzer, MS
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Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USAUniv Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA
机构:
Virginia Commonwealth Univ, Med Coll Virginia, Dept Med, Div Infect Dis, Richmond, VA 23298 USAVirginia Commonwealth Univ, Med Coll Virginia, Dept Med, Div Infect Dis, Richmond, VA 23298 USA
机构:
Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, IsraelTel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel
Balaban, N
Gov, Y
论文数: 0引用数: 0
h-index: 0
机构:Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel
Gov, Y
Bitler, A
论文数: 0引用数: 0
h-index: 0
机构:Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel
Bitler, A
Boelaert, JR
论文数: 0引用数: 0
h-index: 0
机构:Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel
机构:
Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USAUniv Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA
Beenken, KE
Blevins, JS
论文数: 0引用数: 0
h-index: 0
机构:
Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USAUniv Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA
Blevins, JS
Smeltzer, MS
论文数: 0引用数: 0
h-index: 0
机构:
Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USAUniv Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA