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.

/pdf/antimicrobial-peptides-from-design-to-clinical-application-13szirhd.pdf

Antimicrobial Peptides: From Design to Clinical Application

Strategies for improving antimicrobial peptide production.

Enterococcus faecalis, Enterococcus faecium and Staphylococcus aureus are both common commensals and major opportunistic human pathogens. In recent decades, these bacteria have acquired broad resistance to several major classes of antibiotics, including commonly employed glycopeptides. Exemplified by resistance to vancomycin, glycopeptide resistance is mediated through intrinsic gene mutations, and/or transferrable van resistance gene cassette-carrying mobile genetic elements. Here, this review will discuss the epidemiology of vancomycin-resistant Enterococcus and S. aureus in healthcare, community, and agricultural settings, explore vancomycin resistance in the context of van and non-van mediated resistance development and provide insights into alternative therapeutic approaches aimed at treating drug-resistant Enterococcus and S. aureus infections.

/pdf/vancomycin-resistance-in-enterococcus-and-staphylococcus-3slivawo.pdf

Vancomycin Resistance in Enterococcus and Staphylococcus aureus

Osteomyelitis is a destructive disease of bone tissue caused by infection with pathogenic microorganisms. Because of the complex and long‐term abnormal conditions, osteomyelitis is one of the refractory diseases in orthopedics. Currently, anti‐infective therapy is the primary modality for osteomyelitis therapy in addition to thorough surgical debridement. However, bacterial resistance has gradually reduced the benefits of traditional antibiotics, and the development of advanced antibacterial agents has received growing attention. This review introduces the main targets of antibacterial agents for treating osteomyelitis, including bacterial cell wall, cell membrane, intracellular macromolecules, and bacterial energy metabolism, focuses on their mechanisms, and predicts prospects for clinical applications.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202206154

Flourishing Antibacterial Strategies for Osteomyelitis Therapy

Abstract Gram-positive (G + ) bacterial infection is a great burden to both healthcare and community medical resources. As a result of the increasing prevalence of multidrug-resistant G + bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), novel antimicrobial agents must urgently be developed for the treatment of infections caused by G + bacteria. Endolysins are bacteriophage (phage)-encoded enzymes that can specifically hydrolyze the bacterial cell wall and quickly kill bacteria. Bacterial resistance to endolysins is low. Therefore, endolysins are considered promising alternatives for solving the mounting resistance problem. In this review, endolysins derived from phages targeting G + bacteria were classified based on their structural characteristics. The active mechanisms, efficacy, and advantages of endolysins as antibacterial drug candidates were summarized. Moreover, the remarkable potential of phage endolysins in the treatment of G + bacterial infections was described. In addition, the safety of endolysins, challenges, and possible solutions were addressed. Notwithstanding the limitations of endolysins, the trends in development indicate that endolysin-based drugs will be approved in the near future. Overall, this review presents crucial information of the current progress involving endolysins as potential therapeutic agents, and it provides a guideline for biomaterial researchers who are devoting themselves to fighting against bacterial infections. 

/pdf/therapeutic-potential-of-bacteriophage-endolysins-for-1vqx1gmd.pdf

Therapeutic potential of bacteriophage endolysins for infections caused by Gram-positive bacteria

Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), are important effector immune defense molecules in multicellular organisms. AMPs exert their antimicrobial activities through several mechanisms; thus far, induction of drug resistance through AMPs has been regarded as unlikely. Therefore, they have great potential as new generation antimicrobial agents. To date, more than 30 AMP‐related drugs are in the clinical trial phase. In recent years, studies show that some AMPs and conventional antibiotics have synergistic effects. The combined use of AMPs and antibiotics can kill drug‐resistant pathogens, prevent drug resistance, and significantly improve the therapeutic effects of antibiotics. In this review, we discuss the progress in synergistic studies on AMPs and conventional antibiotics. An overview of the current understanding of the functional scope of AMPs, ongoing clinical trials, and challenges in the development processes are also presented.

Antimicrobial peptides, conventional antibiotics, and their synergistic utility for the treatment of drug‐resistant infections

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Antimicrobial peptides, conventional antibiotics, and their synergistic utility for the treatment of drug‐resistant infections