The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms

Area of Science:

• Microbiology
• Infectious Diseases
• Drug Discovery

Background:

• Multidrug-resistant (MDR) and persistent bacteria pose a significant global health threat.
• Novel antimicrobial agents are urgently needed to combat resistant pathogens.
• The human antimicrobial peptide LL-37 serves as a basis for developing enhanced analogs.

Purpose of the Study:

• To develop synthetic antimicrobial and antibiofilm peptides (SAAPs) with improved efficacy over LL-37.
• To evaluate the antimicrobial and antibiofilm activity of SAAP-148 against MDR pathogens.
• To assess the therapeutic potential of SAAP-148 in treating bacterial infections in vivo.

Main Methods:

• Design and synthesis of a panel of SAAPs.
• In vitro evaluation of antimicrobial activity against MDR pathogens under physiological conditions.
• Assessment of antibiofilm activity, including prevention and eradication of established biofilms.
• In vivo efficacy testing of SAAP-148 in a hypromellose ointment formulation on ex vivo human skin and in vivo murine skin models.

Main Results:

• SAAP-148 demonstrated superior in vitro killing of bacteria compared to LL-37 and other known antimicrobial peptides.
• SAAP-148 effectively killed MDR pathogens without evidence of induced resistance.
• The peptide prevented biofilm formation and eradicated established biofilms and persister cells.
• A single treatment with SAAP-148 ointment eradicated acute and established infections caused by MRSA and MDR A. baumannii in skin models.

Conclusions:

• SAAP-148 is a potent synthetic antimicrobial peptide with broad-spectrum activity against MDR bacteria.
• SAAP-148 exhibits significant antibiofilm properties and efficacy against persister cells.
• SAAP-148 demonstrates therapeutic potential for treating challenging bacterial infections, including those associated with biofilms.
• SAAP-148 represents a promising drug candidate for combating antibiotic-resistant bacterial infections.