STAMPs

As one of our lead technology platforms, Specifically-Targeted Antimicrobial Peptides (STAMPs), consist of three functionally-independent peptide regions within a single molecule. STAMPs have the ability to seek out and selectively kill specific microbial pathogens within biofilms while leaving the remainder of the microbial ecosystem undisturbed. This approach represents a quantum improvement over broad-spectrum antibiotics, the overuse/misuse of which has fueled the emergence of drug-resistant bacteria; the so-called "superbugs". We have successfully generated STAMPs targeting a number of human pathogens. Currently, we are focused on developing STAMPs against Streptococcus mutans, the causative agent of tooth decay, and the pathogenic yeast Candida albicans.

Anti-Cavity STAMPs

We have developed several lead STAMP molecules with specific and robust activity against S. mutans, a cavity-causing organism which adheres to the tooth surface and produces enamel-damaging acids after feeding on dietary sugars such as sucrose. Our STAMPs can eliminate S. mutans from within multi-species biofilms (also known as dental plaque) without affecting closely related non-cariogenic oral bacteria (Figs. 1 and 2). Healthy, S. mutans-free biofilms can inhibit future S. mutans colonization and subsequent acid production and cariogenesis. Current efforts are focused on formulation, oral availability, and incorporation of non-peptide STAMP components.

Figure 1. S. mutans, S. sanguinis, and S. gordonii planktonic cells were exposed to 25 µM of the STAMP C16G2 for 1 min.
Surviving CFU per milliliter were detected and compared. Data represent averages of the results of at least three independent experiments. [Copyright © American Society for Microbiology, Antimicrobial Agents and Chemotherapy, November 2006, p. 3651-3657, Vol. 50, No. 11]

We are actively developing STAMPs with specific activity against numerous pathogenic bacteria and fungi, including Pseudomonas aeruginosa, MRSA, VRE, Streptococcus pneumoniae, Clostridium difficile, Listeria monocytogenes, Candida albicans, and the emerging pathogen Acinetobacter baumannii. Preclinical data for one lead molecule indicates potent activity against P. aeruginosa biofilms, and displays synergistic activity with the antibiotic Tobramycin. Our unique rational design platform allows us to design a library of highly-active lead STAMPs against an established, or newly emerging pathogen, in as little as six months.

Figure 2. Binding of STAMP Sm6(L1)B33 to S. mutans biofilms.
Once bound by the STAMP, the S. mutans were effectively eliminated after a few minutes. The STAMP did not bind to biofilms grown from other oral bacteria. [Copyright © American Society for Microbiology, Antimicrobial Agents and Chemotherapy, May 2010, p. 2143-2151, Vol. 54, No. 5]

The pathogenic yeast C. albicans is a classic opportunistic pathogen, known for causing oral and genital thrush and invasive candidiasis. An intact normal flora can help prevent C. albicans infection and re-infection at mucosal surfaces, suggesting STAMPs may be well suited to selectively-eliminate these organisms. As shown in Figure 1, we have developed several pilot STAMP libraries with inhibitory activity against C. albicans, including against the invasive filamentous (hyphal) growth form. We are currently characterizing our lead molecules for safety and efficacy in vitro and in vivo.

Figure 3A

Figure.3—A) Selective binding of peptide 1 to C. albicans hyphae (labeled green). B) Specific killing of C. albicans hyphae which are associated with the pathogenic state of C. albicans (labeled red). C) Binding of peptide 2 to C. albicans biofilm (Labeled green).