Novel antimicrobial peptides against MRSA

Antibiotic resistant bacterial strains represent a global health problem with a strong social and economic impact. As example, the human pathogen Staphylococcus aureus (S. aureus) is a major cause of a wide range of community- and hospital-acquired infections worldwide. Since the introduction of semisynthetic penicillins, such as methicillin or oxacillin the occurrence of methicillin-resistant S. aureus strains (MRSA) has steadily increased and represents now a serious threat to the health especially in hospitalized patients. The recent emergence and transmission of MRSA strains being resistant even to glycopeptides like vancomycin, the antibiotic of choice in the treatment of serious MRSA infections, emphasize the urgent development of novel antibiotic agents against these strains. Antimicrobial peptides (AMPs) are of major interest as a novel source for antibiotics against multiresistant bacterial strains. The main advantage of this class of substances, when considering bacterial resistance, is that they rapidly, within minutes, destroy bacteria in every growth phase. This poperty makes the development of bacterial resistances against AMPs less likely and should make AMPs superior to conventional antibiotics. The antimicrobial activity of most AMPs is due to their ability of perturbing the barrier function of cell membranes by interaction with the membrane matrix, the lipids. Major components of bacterial cell membranes are negatively charged lipids. In contrast, AMPs are cationic and therefore, interact specifically with bacterial cell membranes and not with uncharged mammalian cell membranes. This electrostatic interaction seems to be the initial step of the peptide`s membrane selectivity. In contrast to other bacteria, S. aureus contains an unusual positively charged membrane lipid, namely lysyl-phosphatidylglycerol (lysyl-PG), which seems to make it less sensitive to many AMPs. Concerning MRSA strains, no detailed information about the lipid composition is available to date, although lysyl- PG is known to be a major component of their cytoplasmic membrane. Therefore, we will design novel AMPs with inversed surface charge, which will bind to the positively charged lipids of the MRSA cytoplasmic membrane and in parallel, we will determine the lipid pattern of various MRSA strains to investigate possible changes in lipid pattern upon acquiring multi-drug resistances. This will enable us to design even more effective AMPs towards MRSA.

Antibiotic resistant bacterial strains represent a global health problem with a strong social and economic impact. As example, the human pathogen Staphylococcus aureus (S. aureus) is a major cause of a wide range of community- and hospital-acquired infections worldwide. Since the introduction of semisynthetic penicillins, such as methicillin or oxacillin the occurrence of methicillin-resistant S. aureus strains (MRSA) has steadily increased and represents now a serious threat to the health especially in hospitalized patients. The recent emergence and transmission of MRSA strains being resistant even to glycopeptides like vancomycin, the antibiotic of choice in the treatment of serious MRSA infections, emphasize the urgent development of novel antibiotic agents against these strains. Antimicrobial peptides (AMPs) are of major interest as a novel source for antibiotics against multiresistant bacterial strains. The main advantage of this class of substances, when considering bacterial resistance, is that they rapidly, within minutes, destroy bacteria in every growth phase. This poperty makes the development of bacterial resistances against AMPs less likely and should make AMPs superior to conventional antibiotics. The antimicrobial activity of most AMPs is due to their ability of perturbing the barrier function of cell membranes by interaction with the membrane matrix, the lipids. Major components of bacterial cell membranes are negatively charged lipids. In contrast, AMPs are cationic and therefore, interact specifically with bacterial cell membranes and not with uncharged mammalian cell membranes. This electrostatic interaction seems to be the initial step of the peptide`s membrane selectivity. In contrast to other bacteria, S. aureus contains an unusual positively charged membrane lipid, namely lysyl-phosphatidylglycerol (lysyl-PG), which seems to make it less sensitive to many AMPs. Concerning MRSA strains, no detailed information about the lipid composition is available to date, although lysyl- PG is known to be a major component of their cytoplasmic membrane. Therefore, we will design novel AMPs with inversed surface charge, which will bind to the positively charged lipids of the MRSA cytoplasmic membrane and in parallel, we will determine the lipid pattern of various MRSA strains to investigate possible changes in lipid pattern upon acquiring multi-drug resistances. This will enable us to design even more effective AMPs towards MRSA.