P-113D

P-113D has demonstrated activity against CF patient clinical isolates of bacteria that are resistant to traditional antibiotics. The compound is stable and maintains activity in sputum of CF patients. P-113D was determined to be the smallest histatin fragment which retained antimicrobial activity equivalent to that of the parent compound. Interestingly, synthesizing P113 with D-amino acids gave rise P-113D, a compound that was impervious to enzymatic degradation and maintained the antimicrobial activity of the parent compound. P-113D also has very potent in vitro activity against a variety of Gram negative and positive bacteria including <i>P. aeruginosa</i>, <i>S. aureus</i>, <i>H. influenzae</i>, <i>S. typhimurium</i>, <i>E. coli</i>, <i>S. epidermidis</i>, <i>S. mutans</i> and <i>S. sobrinus</i>. In the case of <i>P. aeruginosa</i> and <i>S. aureus</i>, antibacterial activity has been demonstrated against a variety of CF patient clinical isolates which are resistant to traditional antibiotics. <i>P. aeruginosa</i> isolates that produce thick alginate secretions (mucoid phenotype) are also susceptible to killing by P-113D.

For both bacteria and fungi such as <i>Candida albicans</i>, P-113D has been shown to kill cells as opposed to simply inhibiting their growth. It has been demonstrated that P-113D acts by binding to the cell surface and increasing the permeability of both the outer and inner membranes of the cells of Gram negative bacteria, killing them within seconds.