The antibacterial activity of peptide dendrimers and polymyxin B increases sharply above pH 7.4

Area of Science:

• Microbiology
• Biochemistry
• Materials Science

Background:

• Antimicrobial resistance is a growing global health threat.
• Polycationic antimicrobials, including antimicrobial peptide dendrimers (AMPDs), show promise in combating resistant bacteria.
• The efficacy of AMPDs can be influenced by environmental factors such as pH.

Purpose of the Study:

• To investigate the effect of pH on the antimicrobial activity of AMPDs.
• To elucidate the mechanism behind pH-dependent activity of AMPDs against specific bacterial pathogens.
• To determine if this pH-dependent activity is a general property of polycationic antimicrobials.

Main Methods:

• pH-activity profiling was employed to assess AMPD efficacy.
• Klebsiella pneumoniae and Methicillin-resistant Staphylococcus aureus (MRSA) were used as model pathogens.
• Electrostatic binding interactions between AMPDs and bacterial cells were analyzed at different pH values.

Main Results:

• AMPDs demonstrated significant antimicrobial activity against Klebsiella pneumoniae and MRSA at pH 8.0.
• AMPDs were inactive against these bacteria at pH 7.4.
• Stronger electrostatic binding of AMPDs to bacterial cells was observed at pH 8.0 compared to pH 7.4.

Conclusions:

• The antimicrobial activity of AMPDs is pH-dependent, with enhanced efficacy at higher pH.
• Increased electrostatic binding at higher pH is the primary mechanism for improved AMPD activity.
• This pH-dependent activity may be a general characteristic of polycationic antimicrobials, including polymyxin B.