The characteristics and roles of antimicrobial peptides as potential treatment for antibiotic-resistant pathogens: a review

Abstract

The emergence of antibiotic-resistant bacteria has become a significant and ever-increasing threat to global public health, increasing both morbidity and mortality rates, and the financial burden on health services. Infection by drug-resistant bacteria is anticipated to contribute to the demise of almost 10 million people by the year 2050 unless a competent and effective response is devised to engage with this issue. The emergence and spread of resistance are commonly caused by the excessive or inappropriate use of antibiotics and substandard pharmaceuticals. It arises when pathogens adapt to different conditions and develop self-defence mechanisms. Currently, novel antimicrobial peptides (AMPs) have been reported to be the sole cure for some clinical cases of infectious diseases such as sepsis and skin infections, although these agents may, on occasion, require administration together with an adjunctive low-dose antibiotic. Although AMPs are a promising alternative form of anti-microbial therapy and easily applied in the medical sector, they still have limitations that should not be taken lightly. Hence, this review explores the characteristics, advantages and disadvantages of AMPs for their potential in treating antibiotic-resistant pathogens.

Antimicrobial Peptides—Mechanisms of Action, Antimicrobial Effects and Clinical Applications

“…The critical interaction points between the peptide and the bacterial membrane are electrostatic forces between the cationic AMPs and the negatively charged bacterial surface [ 28 , 29 , 30 ]. The cytoplasmic membranes of Gram-positive and Gram-negative bacteria are rich in phospholipids, phosphatidylglycerol, and cardiolipin, which have negatively charged major groups which strongly attract positively charged AMPs [ 1 , 31 ]. The cationic amphipathic α-helix is one of the most common types of AMP [ 25 ].…”

10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities

“…As global public health faces a looming crisis due to the emergence, evolution, and worldwide spread of antibiotic-resistant bacteria, alternative antibiotic agents with different mechanisms are urgently needed. At this conjuncture, antimicrobial peptides (AMPs), which selectively disrupt the bacterial cell’s membrane, captured attention as highly promising agents for combating drug-resistant bacteria [ 1 , 2 ]. In practice, the administration of AMPs, together with an adjunctive antibiotic, was the sole cure for some cases of infectious diseases, such as sepsis and skin infections [ 1 ].…”

“…At this conjuncture, antimicrobial peptides (AMPs), which selectively disrupt the bacterial cell’s membrane, captured attention as highly promising agents for combating drug-resistant bacteria [ 1 , 2 ]. In practice, the administration of AMPs, together with an adjunctive antibiotic, was the sole cure for some cases of infectious diseases, such as sepsis and skin infections [ 1 ]. Natural AMPs, which are characterized as genetically encoded endogenous antibiotic peptides, have been identified in all domains of life and protect the host from invading pathogens [ 3 , 4 , 5 ].…”

Repurposing HDAC inhibitors to enhance ribonuclease 4 and 7 expression and reduce urinary tract infection

“…Gram-negative bacteria employ several mechanisms to resist killing by AMPs. They express efflux pumps, produce capsule polysaccharides that shield their cell surface, covalently modify their lipopolysaccharide to reduce AMP binding, produce proteases to cleave AMPs, or downregulate AMP expression by host cells ( 21 – 23 ). If RNase 4 or RNase 7 expression is downregulated or silenced in vitro, UPEC attachment to and invasion of bladder urothelial cells increases.…”