Antimicrobialpeptides for combating drug-resistant bacterial infections Antimicrobial peptides (AMPs) represent a crucial component of the innate immune response across diverse life forms, offering a promising avenue in the fight against increasingly prevalent antibiotic resistance作者：DI Andersson·2016·被引用次数：886—The main pathways resulting in transient high-level AMP resistance in bacteria are membrane modifications, increased efflux and proteolytic degradation.. While AMPs are generally considered less susceptible to resistance development compared to conventional antibiotics due to their multi-target action, understanding the mechanisms by which bacteria evolve resistance to these peptides is vital for their effective clinical application.Mechanism of Bacterial Resistance to Antimicrobial Peptides This article delves into the complexities of antimicrobial peptide resistance, exploring the strategies bacteria employ to evade their effects and the implications for future therapeutic approaches.
Bacteria have evolved a sophisticated array of mechanisms to counteract the action of AMPs. These strategies often involve modifications to the bacterial cell surface, which is the primary point of interaction for many AMPs.2025年8月5日—Bacteria differ in their inherent susceptibility and resistance mechanismsto these peptides when responding to the antimicrobial effects of ...
Modifications to Cell Surface Properties: A primary defense mechanism involves altering the electrostatic properties of the bacterial cell envelope. Many AMPs, particularly cationic ones, initially bind to negatively charged components on the bacterial surface, such as phospholipids and lipopolysaccharides作者：TW Cullen·2015·被引用次数：468—We have found that human gut microbes from all dominant phyla are resistant to high levels of inflammation-associatedantimicrobial peptides(AMPs).. Bacteria can counter this by reducing the overall negative charge of their membraneResistance Mechanisms to Antimicrobial Peptides in Gram .... This can be achieved through various means, including:
* Phospholipid Modification: Changes in the composition and arrangement of membrane phospholipids can reduce the affinity of AMPs for the bacterial surface.作者：M Abdi·2019·被引用次数：78—Bacterial cell envelope modification is the main cause of bacterial resistanceto Antimicrobial Peptides Many bacterial proteins degrade or ... For instance, alterations in phosphatidylglycerol (PG) or diphosphatidylglycerol (cardiolipin) content can play a role.
* Altered Cell Surface Charge: Upregulation of positively charged molecules or downregulation of negatively charged ones on the outer membrane can repel cationic AMPs.
Efflux Pumps and Proteolytic Degradation: Beyond surface modifications, bacteria can also employ active transport systems and enzymatic degradation to neutralize AMPs.
* Active Efflux: Bacteria can utilize efflux pumps to actively transport AMPs out of the cell, preventing them from reaching their intracellular targets. This mechanism is well-known for its role in antibiotic resistance and can also confer resistance to AMPs.Antimicrobial peptide resistance mechanisms of human ...
* Proteolytic Degradation: Some bacteria produce proteases that can cleave and inactivate AMPs. While AMPs are generally more resistant to proteases than traditional antibiotics, the presence of specific bacterial enzymes can significantly reduce their efficacy.
Intracellular Resistance Mechanisms: While less common than surface-based defenses, some bacteria may also develop intracellular mechanisms to resist AMPs, such as altering metabolic pathways that influence AMP susceptibility or resilience. Research into the intricate relationship between metabolic genes and AMP resistance is ongoing, highlighting the complex interplay between cellular processes and defense against these antimicrobial agents.
The development of resistance to AMPs is often a complex, multi-step evolutionary process. Unlike conventional antibiotics, which typically target a single specific pathway, AMPs often act on multiple targets. This multi-target action is believed to inherently reduce the likelihood of resistance evolution compared to antibioticsAntimicrobial Peptides in the Global Microbiome: Biosynthetic .... However, resistance can still emerge through various genetic mutations and adaptive strategies.
* Epistatic Interactions: The evolution of resistance can be shaped by epistatic interactions, where the effect of one gene mutation is dependent on the presence of other gene mutations. This can lead to synergistic effects, creating a more robust resistance phenotypeAntimicrobial Peptides: Features, Action, and Their ....
* Acquired Resistance: Similar to antibiotic resistance, resistance to AMPs can be acquired through mutations in chromosomal genes or horizontal gene transfer, allowing bacteria to adapt and survive in the presence of these peptides作者：B El Shazely·2020·被引用次数：112—Antimicrobial peptides(AMPs) have been proposed as a promising class of new antimicrobials partly because they are less susceptible to ....
While the potential for resistance development is a concern, AMPs remain a highly promising class of antimicrobials, particularly in addressing the global crisis of antibiotic resistanceAntimicrobial Peptides in the Global Microbiome: Biosynthetic .... Their broad-spectrum activity and unique mechanisms of action offer a potential solution where conventional drugs fail.
* Lower Risk of Resistance: The inherent multi-target nature of AMPs generally leads to a lower risk of resistance evolution compared to antibiotics. This characteristic makes them attractive candidates for new therapeutic strategies.Could the use of Antimicrobial Peptides create resistance to ...
* Addressing the Antibiotic Resistance Crisis: AMPs are viewed as a game-changer in the epic battle against antibiotic resistance, offering a potential alternative or adjunct therapy.
* Challenges and Opportunities: Despite their promise, challenges such as poor proteolytic resistance in clinical settings need to be addressed.2017年2月28日—Resistance to an AMP or AMP-like drugmay not only contribute to increasing multi-resistancebut also disarm the human immune system. This would ... Ongoing research focuses on designing AMPs with enhanced stability and efficacy, as well as understanding the complete spectrum of resistance mechanisms to optimize their therapeutic use.
In conclusion, while bacteria can and do develop resistance to antimicrobial peptides through various evolutionary strategies, the inherent properties of AMPs suggest a lower propensity for resistance compared to traditional antibiotics. Continued research into the mechanisms of AMP resistance, coupled with the development of more robust AMP-based therapies, holds significant potential for combating the growing threat of drug-resistant infections.
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