Abstract
Infection of multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, brings public health issues and causes economic burden. Pathogenic bacteria develop several methods to resist antibiotic killing or inhibition, such as mutation of antibiotic function sites, activation of drug efflux pumps, and enzyme-mediated drug degradation. Antibiotic resistance components can be transferred between bacteria by mobile genetic elements including plasmids, transposons, and integrons, as well as bacteriophages. The development of antibiotic resistance limits the treatment options for bacterial infection, especially for MDR bacteria. Therefore, novel or alternative antibacterial agents are urgently needed. Antimicrobial peptides (AMPs) display multiple killing mechanisms against bacterial infections, including directly bactericidal activity and immunomodulatory function, as potential alternatives to antibiotics. In this review, the development of antibiotic resistance, the killing mechanisms of AMPs, and especially, the design, optimization, and delivery of AMPs are reviewed. Strategies such as structural change, amino acid substitution, conjugation with cell-penetration peptide, terminal acetylation and amidation, and encapsulation with nanoparticles will improve the antimicrobial efficacy, reduce toxicity, and accomplish local delivery of AMPs. In addition, clinical trials in AMP studies or applications of AMPs within the last five years were summarized. Overall, AMPs display diverse mechanisms of action against infection of pathogenic bacteria, and future research studies and clinical investigations will accelerate AMP application.
Highlights
According to the 2019 antibiotic resistance report by the Center for Disease Control and Prevention (CDC), more than 2.8 million cases of antibiotic-resistant infection occur in the United States, with 35,000 infection-caused deaths [1]
Research studies showed that DP7, an Antimicrobial peptides (AMPs) designed in silico, showed broad-spectrum antimicrobial activity against MDR bacteria, such as P. aeruginosa [102]
Overuse and misuse of antibiotics accelerate the development of antibiotic resistance
Summary
According to the 2019 antibiotic resistance report by the Center for Disease Control and Prevention (CDC), more than 2.8 million cases of antibiotic-resistant infection occur in the United States, with 35,000 infection-caused deaths [1]. Antibiotics are prescribed for viral infections, which may not be necessary. A meta-analysis study showed that initial inappropriate antibiotic therapy in hospitalized patients with Gram-negative bacterial infections can cause adverse outcomes including mortality, with an unadjusted summary odds ratio [OR] 2.66 and 95% confidence interval [CI] 2.12–3.35 [11]. A recent report showed that the COVID-19 pandemic caused a spread of MDR bacterial infections including MRSA, carbapenem-resistant Acinetobacter baumannii, and fungi. A review report with the analysis of 10 African countries showed that antibiotics such as amoxicillin and ampicillin were commonly prescribed antibiotics for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [13]. Antimicrobial peptides (AMPs) are expressed by most living organisms and play important roles in defending against bacterial, viral and fungal infections [16–18], as well as adaptive immunity during the development of cancers and autoimmune diseases [19,20]. Some clinical trials for the past five years and applications of AMPs are reviewed
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