Bacterial infection diseases severely threaten human health at all times. Sepsis is a systemic inflammatory response syndrome following bacterial infection with a high mortality rate and limited therapeutic options. Current treatment of sepsis is based on controlling infection, hemodynamic support, modulating immune response, and supportive care. However, it is becoming less effective owing to the emergence of many antibiotic-resistant bacteria worldwide. Three classes of antibiotic-resistant pathogens are emerging as major threats to public health: 1) methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA); 2) multidrug-resistant (MDR) and pandrug-resistant Gram-negative bacteria; and 3) MDR and extensively drug-resistant strains of Mycobacterium tuberculosis. Thus, there is a vital need for new effective therapeutics to conquer infections caused by drug-resistant bacteria. Cationic antimicrobial peptides (AMPs), are a class of small cationic peptide with potent antimicrobial activity, and have been isolated from various organisms, including microorganisms, plants, invertebrates, and vertebrates. In addition to its direct antimicrobial activity, AMPs have a variety of other functions, such as neutrolizition of LPS, chemoattraction of immune cells, release of histamine from mast cells, modulation of inflammation, and induction of angiogenesis. Due to their unique mechanism of action, AMPs have become important potential candidates for therapeutic agents and have been considered as viable alternatives to conventional antibiotics against antibiotic-resistant pathogens. However, their comparatively high toxicity toward eukaryotic cells and poor efficacy in vivo hamper their clinical application. OH-CATH30, a novel cathelicidin peptide deduced from the king cobra, possesses potent bactericidal activity and low hemolysis in vitro. The objective of this study is to evaluate the direct antibacterial activity and immunomoddulatory properties of OH-CATH30. We fist investigated the direct antibacterial activity of OH-CATH30 and its analogs against drug-resistant bacteria in vitro and in vivo. The minimal inhibitory concentrations (MICs) of OH-CATH30 and OH-CM6 ranged from 1.56 to 12.5 μg/ml against drug-resistant clinical isolates of several pathogenic species, including Escherichia coli, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. The MICs of OH-CATH30 and OH-CM6 were slightly altered in the presence of 25% human serum.
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