An Update on the Therapeutic Potential of Antimicrobial Peptides against Acinetobacter baumannii Infections

Abstract

The rise in antibiotic-resistant strains of clinically important pathogens is a major threat to global health. The World Health Organization (WHO) has recognized the urgent need to develop alternative treatments to address the growing list of priority pathogens. Antimicrobial peptides (AMPs) rank among the suggested options with proven activity and high potential to be developed into effective drugs. Many AMPs are naturally produced by living organisms protecting the host against pathogens as a part of their innate immunity. Mechanisms associated with AMP actions include cell membrane disruption, cell wall weakening, protein synthesis inhibition, and interference in nucleic acid dynamics, inducing apoptosis and necrosis. Acinetobacter baumannii is a critical pathogen, as severe clinical implications have developed from isolates resistant to current antibiotic treatments and conventional control procedures, such as UV light, disinfectants, and drying. Here, we review the natural AMPs representing primary candidates for new anti-A. baumannii drugs in post-antibiotic-era and present computational tools to develop the next generation of AMPs with greater microbicidal activity and reduced toxicity.

Keywords: AMP; Acinetobacter baumannii; mechanism of action; resistance.

Figure 1

Number of articles selected according to the year of publication.

Figure 2

Antimicrobial peptide (AMP) mechanisms on bacterial cells: (A) AMPs directly affect bacterial membrane and intracellular targets and disrupt lipid receptors and membrane-bound machinery. (B) AMPs indirectly trigger the activation and chemoattraction of immune cells.

Figure 3

AMP mechanisms of action on bacterial membranes: (A) In the barrel-staved model, the accumulation of AMPs inserted into the membrane bilayer forms a pore. (B) In the carpet model, AMPs accumulate on the surface until a critical concentration displays detergent behavior to form micelles. (C) Accumulated AMPs inserted in vertical and bent orientations form a pore in the toroidal pore model. (D) Positively charged AMPs interact with negatively charged cell membranes adsorbing, leading to electroporation. (E) AMP interaction can interfere with membrane thickening, making the membrane more fragile. (F) Non-lytic membrane depolarization. (G) AMP oxidizes membrane lipids, leading to reactive oxygen species and increased lysis and permeability. (H) AMP generation of the non-bilayer intermediate that interacts with the membrane.