Abstract
Antimicrobial peptide research remains active not only because of the growing antibiotic resistance problem but also our desire to understand the role of innate immune peptides in host defense. While numerous peptides are currently under active development for topical use, this article highlights peptides with systemic efficacy. The scaffolds of these peptides range from linear to cyclic forms. The neutropenic mouse model is well established to illustrate antimicrobial efficacy from direct killing. The majority of tests, however, are conducted using normal mice so that both direct antimicrobial and immune regulatory effects can be characterized. These systemic examples underscore the possibility of adding new candidates to the list of the existing peptide antibiotics to more effectively combat antibiotic-resistant bacteria, fungi, and parasites.
Highlights
D Keywords e Antibiotics; antimicrobial peptides; peptide design; MIC; PK; PD; systemic efficacy; toxicity; intravenous c injection van 1
Our current knowledge implies that basic amino acids are key to the inhibition and killing of Gram-negative bacteria, whereas hydrophobic amino acids are critical to lin eliminating Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) [14]
Concluding remarks and future directions le There is a clear need for systemic antimicrobials to treat bloodstream infections caused by antibioticresistant pathogens, such as bacteria, fungi, and parasites
Summary
After peptide optimization, it is necessary to test peptide antimicrobial robustness. We observed a significant decrease in bacterial burden (1-4 logs) in a variety of c murine organs, including the spleen, lung, kidney, and liver, when treated either intraperitoneally or n intravenously [27] These results document direct antimicrobial efficacy for AMPs. a Other laboratories have primarily used normal (non-neutropenic) mice to test peptide efficacy. Api137 (an apidaecin derived peptide) showed a dose-dependent protection of the CD-1 mice (67 % survival over 5 days) from E. coli ATCC 25922 infection when treated subcutaneously but not intravenously [42]. While the plasma level of D-horine remains above the MIC (4 μM) for about one hour, the L-form of horine is rapidly degraded The fact that both peptides demonstrate in vivo efficacy indicates rapid bacterial killing by horine, consistent with in vitro findings [27].
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