Antimicrobial peptidesfor combating drug-resistant bacterial infections Antimicrobial peptides (AMPs) represent a promising frontier in the fight against the escalating global health threat of antimicrobial resistance. Unlike traditional antibiotics, AMPs possess unique multi-target mechanisms that theoretically reduce the likelihood of resistance development.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. However, as research progresses, it has become clear that bacteria are not entirely defenseless against these novel agents, and understanding the nuances of antimicrobial peptides resistance is crucial for their effective clinical application.We hypothesise that the membrane properties play a central role in the development ofresistanceto the action of AMPs and that, understanding how phospholipid ... This is particularly important given the context of increasing antibiotic resistance, where AMPs are increasingly viewed as a vital component of future therapeutic strategies.
Bacteria have evolved a diverse array of strategies to evade or neutralize the effects of AMPs. These mechanisms can broadly be categorized into alterations at the bacterial surface, intracellular modifications, and enzymatic degradation.
One primary line of defense involves altering the physico-chemical properties of the bacterial surface. Many AMPs exert their action through electrostatic attraction to the negatively charged bacterial membraneAntimicrobial Peptides: The Game-Changer in the Epic .... Bacteria can counteract this by modifying their surface charge, for instance, by increasing the abundance of positively charged molecules or altering the lipid composition of their membranes, such as through phospholipid modification2018年6月29日—Phospholipid modification is the main mechanism ofresistanceto AMPs at this stage. PG and diphosphatidylglycerol (also called cardiolipin) as the most abundant phospholipids in bacterial membranes have anionic head groups that electrostatically attract AMPs. As aresistancemechanism, S.. This can limit the initial interaction of AMPs with their target.
Another significant resistance mechanism is the modification or degradation of AMPs themselves2018年6月29日—Phospholipid modification is the main mechanism ofresistanceto AMPs at this stage. PG and diphosphatidylglycerol (also called cardiolipin) as the most abundant phospholipids in bacterial membranes have anionic head groups that electrostatically attract AMPs. As aresistancemechanism, S.. Some bacteria secrete proteases capable of cleaving and inactivating AMPs, thus rendering them ineffective. Additionally, efflux pumps, which are cellular machinery designed to expel foreign substances, can also contribute to resistance by actively transporting AMPs out of the bacterial cell before they can reach their intracellular targets or disrupt the membrane.
The emergence of resistance to AMPs is not merely a passive biological process but also an evolutionary one2018年6月29日—Phospholipid modification is the main mechanism ofresistanceto AMPs at this stage. PG and diphosphatidylglycerol (also called cardiolipin) as the most abundant phospholipids in bacterial membranes have anionic head groups that electrostatically attract AMPs. As aresistancemechanism, S.. Bacteria can develop resistance through genetic mutations in chromosomal genes or through horizontal gene transfer, acquiring resistance genes from other bacteria.Antimicrobial peptides: Application informed by evolution While AMPs are generally considered to have a slower rate of resistance development compared to conventional antibiotics due to their multi-target action, the potential for resistance evolution remains a significant concern. Studies exploring the evolutionary constraints on AMP resistance highlight that even subtle genetic variations can dramatically alter a bacterium's susceptibility. Understanding these evolutionary dynamics is key to designing AMPs that are less prone to resistance, or to developing strategies that inhibit resistance developmentThe antimicrobial peptide LI14 combats multidrug-resistant ....
Despite the challenges posed by antimicrobial peptides resistance, AMPs continue to hold immense promise in combating the broader crisis of antimicrobial resistance (AMR). Their broad-spectrum activity and novel mechanisms of action make them valuable candidates for treating infections caused by drug-resistant pathogens. Researchers are actively exploring various avenues to harness the full potential of AMPs, including their use in combination therapies, their modification to enhance stability and reduce susceptibility to degradation, and the discovery of new AMPs with superior efficacy and reduced resistance potential. The inherent advantages of AMPs over traditional antibiotics, such as their rapid killing rates and the perceived slower development of resistance, underscore their role as a potential game-changer in the ongoing battle against microbial resistance作者：HS Joo·2016·被引用次数：421—Mechanisms of resistance to AMPs are widespread in bacteria. Many of those are based on changes in the physico-chemical properties of surface ....
While AMPs offer a compelling alternative to conventional antibiotics, their widespread clinical application faces hurdles. These include issues related to stability, selectivity (ensuring they target bacteria without harming host cells), and the very real possibility of resistance development.Antimicrobial Peptides: Mechanisms of Action and Resistance Addressing poor proteolytic resistance is an urgent problem that needs to be solved for successful clinical use. Future research will likely focus on optimizing AMP design, developing delivery systems that protect AMPs from degradation, and implementing strategies to mitigate resistance evolution.Molecular Mechanisms of Bacterial Resistance to ... By understanding the intricate mechanisms of AMP resistance and the evolutionary pathways bacteria employ, scientists can work towards developing next-generation antimicrobial peptides that effectively combat infections and preserve their therapeutic utility in the face of evolving microbial threats.
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