Disclosed are antimicrobial peptides with useful or superior properties such as antimicrobial activity, desirable levels of hemolysis, and advantageous therapeutic index against various microorganisms, especially Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus. Also provided are methods of to control microbial growth and pharmaceutical compositions to treat or prevent microbial infections. Certain peptides are disclosed utilizing a structure-based rational modification of antimicrobial peptide D1, with single D-/L-amino acid substitutions or charged residue substitutions in or near the center of the peptide on the nonpolar or polar face, or peptides with one or more amino acids in the D configuration, and peptides with all amino acids in the D configuration. Modified peptide analogs herein can demonstrate one or more properties such as improved antimicrobial activity, specificity, and resistance to degradation. Compositions disclosed herein are useful as antibiotics, including as broad spectrum antibiotics.
