Antimicrobial peptides: mechanism of action, activity and clinical potential

Zhang, Qiyu; Ye, Zhibin; Meng, Yueming; Hong, Xiangyu; Shao, Gang; Ma, Junjie; Cheng, Xurui; Li, Jun; Kang, Jian; Fu, Caiyun

doi:10.1186/s40779-021-00343-2

Cited by 271 publications

(203 citation statements)

References 378 publications

(396 reference statements)

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“…However, three strains (A. ursingii KR1178, A. ursingii KR1181 and A. johnsonii KR1186) remained sensitive to serum even in the presence of OmCI. This suggests that other factors, such as antimicrobial peptides like LL-37 (52) or lysozyme, might be involved in the killing of Acinetobacter, as previously documented (35). To escape complement-mediated lysis pathogens bind complement inhibitors, mainly FH and C4BP.…”

Section: Discussionmentioning

confidence: 67%

Clinical Isolates of Acinetobacter spp. Are Highly Serum Resistant Despite Efficient Recognition by the Complement System

et al. 2022

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Gram-negative bacteria from the genus Acinetobacter are responsible for life-threating hospital-related infections such as pneumonia, septicemia, and meningitis, especially in immunocompromised patients. Worryingly, Acinetobacter have become multi- and extensively drug resistant (MDR/XDR) over the last few decades. The complement system is the first line of defense against microbes, thus it is highly important to increase our understanding of evasion mechanisms used by Acinetobacter spp. Here, we studied clinical isolates of Acinetobacter spp. (n=50), aiming to characterize their recognition by the complement system. Most isolates tested survived 1 h incubation in 30% serum, and only 8 isolates had a lower survival rate, yet none of those isolates were fully killed. Intriguingly, four isolates survived in human whole blood containing all cell component. Their survival was, however, significantly reduced. Flow cytometry analyses revealed that most of the isolates were detected by human IgG and IgM. Interestingly, we could not detect any significant concentration of deposited C1q, despite observing C4b deposition that was abolished in C1q-deficient serum, indicating transient binding of C1q to bacteria. Moreover, several isolates were recognized by MBL, with C4b deposition abolished in MBL-deficient serum. C3b was deposited on most isolates, but this was not, however, seen with respect to C5b and formation of the membrane attack complex (MAC), indicating that many isolates could avoid complement-mediated lysis. India ink staining showed that isolates were capsulated, and capsule thickness varied significantly between isolates. Studies performed on a wild-type strain and capsule mutant strains, demonstrated that the production of a capsular polysaccharide is one mechanism that mediates resistance to complement-mediated bactericidal activity by preventing MAC deposition and lysis. Our data showed that most clinical Acinetobacter spp. isolates are highly serum resistant despite being efficiently recognized by the complement system.

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Section: Discussionmentioning

confidence: 67%

Clinical Isolates of Acinetobacter spp. Are Highly Serum Resistant Despite Efficient Recognition by the Complement System

et al. 2022

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“…In this study, we designed a series of derivatives from RW-BP100 and screened out the ideal candidate RW-BP100-4D, which showed relatively low cytotoxicity and the best antimicrobial activity. Generally, the activity of AMP is infuenced by many factors, such as peptide length, net charge, hydrophobicity and secondary structure ( Zhang et al, 2021 ). Since single D -amino acid transformation does not alter the length and net charge of the parental peptide, the enhanced antimicrobial activity of RW-BP100-4D in this study may be largely due to the variation of peptide hydrophobicity or secondary structure, thus leading to a stronger binding affinity with the anionic components on the microbial membrane, such as LPS of Gram-negative bacteria, lipoteichoic acid of Gram-positive bacteria and mannan of fungi ( Zhang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

RW-BP100-4D, a Promising Antimicrobial Candidate With Broad-Spectrum Bactericidal Activity

Tong

Wei

et al. 2022

Front. Microbiol.

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With the rapid emergence and dissemination of antimicrobial resistance (AMR) genes in bacteria from animal, animal-derived food and human clinic, it is of great significance to develop new approaches to combat the multidrug-resistant bacteria. This study presented a short linear antimicrobial peptide RW-BP100-4D, which was derived from RW-BP100 (RRLFRRILRWL-NH2) by transforming the N-terminal 4th amino acid from L- to D-enantiomer. This modification remarkably reduced the peptide cytotoxicity to mammalian cells, as indicated by hemolytic and cytotoxicity assays. Meanwhile, the antimicrobial activity of RW-BP100-4D was improved against a more variety of Gram-positive and Gram-negative bacteria (sensitive and resistant) as well as fungi. Also, RW-BP100-4D showed strong in vitro anti-biofilm activity in a concentration-dependent manner, including inhibition of the biofilm-formation and dispersion of the mature biofilms of Staphylococcus aureus. RW-BP100-4D could be efficiently uptaken by bovine mammary epithelial cells (MAC-T) cells to eliminate the intracellular S. aureus ATCC29213 and Salmonella enterica ATCC13076. Moreover, RW-BP100-4D was highly effective in food disinfection of multiple bacterial contamination (including S. aureus, Listeria monocytogenesis, Escherichia coli O157: H7, Campylobacter jejuni, S. enterica, and Shewanella putrefaction, 3.61 ± 0.063 log reduction) on chicken meat, and could kill 99.99% of the methicillin-resistant Staphylococcus aureus (MRSA) strain in the mouse skin infection model. In summary, RW-BP100-4D is a promising antimicrobial candidate for application on food disinfection and local infection treatment. However, the protease-sensitivity of RW-BP100-4D and toxic effect at higher doses reduced the therapeutic effect of the candidate peptide in vivo and should be improved in the future studies.

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“…AMPs are small effector molecules produced naturally or synthetically ( Tan et al, 2021 ), such as cathelicidins, defensins, and hepcidin ( Alcayaga-Miranda et al, 2017 ). They exhibit direct bactericidal properties by physically destroying microbial lipid bilayers to release cell contents ( Zhang et al, 2021a ). Antimicrobial NPs (metal NPs, semi-conductive NPs, and organic NPs) are promising antimicrobial agents, the underlying basic mechanism of which is related to reactive oxygen species-induced interruption of bacteria membranes ( Reshma et al, 2017 ; Calabrese et al, 2022 ).…”

Section: Microbial Disease Therapeuticsmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosome Therapy of Microbial Diseases: From Bench to Bed

Wu¹,

Jin²,

Ding³

et al. 2022

Front. Microbiol.

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Microbial diseases are a global health threat, leading to tremendous casualties and economic losses. The strategy to treat microbial diseases falls into two broad categories: pathogen-directed therapy (PDT) and host-directed therapy (HDT). As the typical PDT, antibiotics or antiviral drugs directly attack bacteria or viruses through discerning specific molecules. However, drug abuse could result in antimicrobial resistance and increase infectious disease morbidity. Recently, the exosome therapy, as a HDT, has attracted extensive attentions for its potential in limiting infectious complications and targeted drug delivery. Mesenchymal stem cell-derived exosomes (MSC-Exos) are the most broadly investigated. In this review, we mainly focus on the development and recent advances of the application of MSC-Exos on microbial diseases. The review starts with the difficulties and current strategies in antimicrobial treatments, followed by a comprehensive overview of exosomes in aspect of isolation, identification, contents, and applications. Then, the underlying mechanisms of the MSC-Exo therapy in microbial diseases are discussed in depth, mainly including immunomodulation, repression of excessive inflammation, and promotion of tissue regeneration. In addition, we highlight the latest progress in the clinical translation of the MSC-Exo therapy, by summarizing related clinical trials, routes of administration, and exosome modifications. This review will provide fundamental insights and future perspectives on MSC-Exo therapy in microbial diseases from bench to bedside.

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Antimicrobial peptides: mechanism of action, activity and clinical potential

Cited by 271 publications

References 378 publications

Clinical Isolates of Acinetobacter spp. Are Highly Serum Resistant Despite Efficient Recognition by the Complement System

Clinical Isolates of Acinetobacter spp. Are Highly Serum Resistant Despite Efficient Recognition by the Complement System

RW-BP100-4D, a Promising Antimicrobial Candidate With Broad-Spectrum Bactericidal Activity

Mesenchymal Stem Cell-Derived Exosome Therapy of Microbial Diseases: From Bench to Bed

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