Beta‐lactam resistance and the effectiveness of antimicrobial peptides against KPC‐producing bacteria

Abstract

Bacterial resistance is a problem that is giving serious cause for concern because bacterial strains such as Acinetobacter baumannii and Pseudomonas aeruginosa are difficult to treat and highly opportunistic. These bacteria easily acquire resistance genes even from other species, which confers greater persistence and tolerance towards conventional antibiotics. These bacteria have the highest death rate in hospitalized intensive care patients, so strong measures must be taken. In this review, we focus on the use of antimicrobial peptides (AMPs) as an alternative to traditional drugs, due to their rapid action and lower risk of generating resistance by microorganisms. We also present an overview of beta-lactams and explicitly explain the activity of AMPs against carbapenemase-producing bacteria as potential alternative agents for infection control.

Recent advances in the development of antimicrobial peptides against ESKAPE pathogens

“…Predominantly, infections and fatalities in healthcare settings are attributed to opportunistic bacteria, notably carbapenem-resistant A. baumannii and P. aeruginosa . Often, inadequate disinfection practices lead to the persistence of strains carrying resistance plasmids, exacerbating diseases and giving rise to frequently incurable co-infections [ 2 ].ESKAPE pathogens have been designated priority status by the World Health Organization, each presenting unique resistance profiles, thereby constituting a pivotal concern within the global health landscape [ 3 , 4 ]. These bacteria possess a range of characteristics that make them particularly difficult to combat, including their adeptness at forming biofilms, which enable them to adhere to surfaces and evade antimicrobial treatments effectively [ 1 ].…”

The Challenge of Overcoming Antibiotic Resistance in Carbapenem-Resistant Gram-Negative Bacteria: “Attack on Titan”

“…Their rapid bactericidal action, low resistance, and multifunctional mechanism of action make them one of the most promising alternatives to antibiotics [ 118 ]. The bactericidal action of AMPs involves the activation of two main different mechanisms: the depolarization and permeabilization of the bacterial membrane or the inhibition of essential intracellular functions without membrane rupture (e.g., by nucleic acid binding) [ 119 ]. A large number of antimicrobial peptides have been identified, each with a unique spectrum of activity and a different mechanism of action [ 119 ].…”

“…The bactericidal action of AMPs involves the activation of two main different mechanisms: the depolarization and permeabilization of the bacterial membrane or the inhibition of essential intracellular functions without membrane rupture (e.g., by nucleic acid binding) [ 119 ]. A large number of antimicrobial peptides have been identified, each with a unique spectrum of activity and a different mechanism of action [ 119 ]. Although many antimicrobial peptides have been identified, clinical use of AMPs remains limited due to their limited stability and high susceptibility to protease degradation.…”

Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo

“…Antimicrobial peptides (AMPs) protect the host from pathogens as part of innate immunity. 8 AMPs can eliminate multiple and pan-resistant bacteria, 9 and new peptide biotechnologies and targeted transport increase the antimicrobial activity of AMPs. 10 Most AMPs have less than 50 amino acids, and the current AMPs are against drug-resistant A. baumannii include cathepsins, defensins, 11 frog antimicrobial peptides, and insect antimicrobial peptides, 12 modified peptides based on tilapia antimicrobial 2, 13 and other natural or engineered small molecular proteins.…”