Advances on chemically modified antimicrobial peptides for generating peptide antibiotics

2021 ◽  
Author(s):  
Samilla Rezende ◽  
karen k.n. oshiro ◽  
Nelson Junior ◽  
Octavio L. Franco ◽  
Marlon Henrique Cardoso
Keyword(s):  
Clinical Trials ◽  
Antimicrobial Peptides ◽  
Bacterial Infections ◽  
Peptide Antibiotics ◽  
Antibiotic Resistant ◽  
Chemically Modified

Antimicrobial peptides (AMPs) are pinpointed as promising molecules against antibiotic-resistant bacterial infections. Nevertheless, there is a discrepancy between the AMP sequences generated and the tangible outcomes in clinical trials. AMPs’...

scholarly journals Antimicrobial peptides: mechanism of action, activity and clinical potential

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Qi-Yu Zhang ◽  
Zhi-Bin Yan ◽  
Yue-Ming Meng ◽  
Xiang-Yu Hong ◽  
Gang Shao ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Infections ◽  
Biological Activities ◽  
Structural Characteristics ◽  
Rapid Evolution ◽  
High Specificity ◽  
Mechanisms Of Action ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Clinical Potential

AbstractThe management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

scholarly journals Epithelial Antimicrobial Peptides: Review and Significance for Oral Applications

1998 ◽  
Vol 9 (4) ◽  
pp. 399-414 ◽  
Author(s):  
A. Weinberg ◽  
S. Krisanaprakornkit ◽  
B.A. Dale
Keyword(s):  
Antimicrobial Peptides ◽  
Oral Mucosa ◽  
Bacterial Infections ◽  
Periodontal Diseases ◽  
Mucosal Barrier ◽  
Human Neutrophils ◽  
Bacterial Invasion ◽  
Peptide Antibiotics ◽  
Natural Flora ◽  
Micro Organisms

Epithelial tissues provide the first line of defense between an organism and the environment. Disruption of this barrier leads to bacterial invasion and subsequent inflammation. This is precisely the situation existing in the human oral cavity, where tissues are constantly exposed to a variety of microbial challenges that can lead to bacterially induced periodontal diseases, and to infections of the oral mucosa by bacteria, fungi, and viruses. With the recent discoveries of host-derived peptide antibiotics in mammalian mucosal epithelium, a new line of investigation is emerging to test the hypothesis that one class of these peptides, called " β-defensins", functions to protect the host against microbial pathogenesis at these critical, confrontational sites. In that light, impairment of β-defensin activity has recently been implicated in chronic bacterial infections in cystic fibrosis patients. The first direct evidence of expression of defensin peptides in the oral mucosa was the identification of a novel epithelial β-defensin in mammalian tongue. It was shown to be upregulated in inflammation, suggesting that it participates in host defense. It is theorized that epithelial cell-derived antimicrobial peptides function to keep the natural flora of micro-organisms in a steady state in different niches such as the skin, the intestines, the airway, the endocervix, and the mouth. There is now evidence indicating that normal gingival epithelial cells and tissues express two β-defensins, hBD- I and the newly described hBD-2. In addition, a cathelin-class antimicrobial peptide, designated LL-37 and found in human neutrophils, is also expressed in skin and gingiva. It is highly likely that these and/or other epithelial antimicrobial peptides play an important role in determining the outcome of the host-pathogen interaction at the oral mucosal barrier, and that they may have important future applications in antibiotic treatment.

scholarly journals Different effects of transcriptional regulators MarA, SoxS and Rob on susceptibility of Escherichia coli to cationic antimicrobial peptides (CAMPs): Rob-dependent CAMP induction of the marRAB operon

Microbiology ◽  
2010 ◽  
Vol 156 (2) ◽  
pp. 570-578 ◽  
Author(s):  
Douglas M. Warner ◽  
Stuart B. Levy
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptides ◽  
Bacterial Infections ◽  
Transcriptional Regulators ◽  
Polymyxin B ◽  
Cationic Antimicrobial Peptides ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Camp Induction ◽  
Increased Susceptibility

Cationic antimicrobial peptides (CAMPs), a component of the mammalian immune system, protect the host from bacterial infections. The roles of the Escherichia coli transcriptional regulators MarA, SoxS and Rob in susceptibility to these peptides were examined. Overexpression of marA, either in an antibiotic-resistant marR mutant or from a plasmid, decreased bacterial susceptibility to CAMPs. Overexpression of the soxS gene from a plasmid, which decreased susceptibility to antibiotics, unexpectedly caused no decrease in CAMP susceptibility; instead it produced increased susceptibility to different CAMPs. Deletion or overexpression of rob had little effect on CAMP susceptibility. The marRAB operon was upregulated when E. coli was incubated in sublethal amounts of CAMPs polymyxin B, LL-37 or human β-defensin-1; however, this upregulation required Rob. Deletion of acrAB increased bacterial susceptibility to polymyxin B, LL-37 and human β-defensin-1 peptides. Deletion of tolC yielded an even greater increase in susceptibility to these peptides and also led to increased susceptibility to human α-defensin-2. Inhibition of cellular proton-motive force increased peptide susceptibility for wild-type and acrAB deletion strains; however, it decreased susceptibility of tolC mutants. These findings demonstrate that CAMPs are both inducers of marA-mediated drug resistance through interaction with Rob and also substrates for efflux in E. coli. The three related transcriptional regulators show different effects on bacterial cell susceptibility to CAMPs.

scholarly journals Antibiotic-Resistant Bacteria in Clams—A Study on Mussels in the River Rhine

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 571
Author(s):  
Nicole Zacharias ◽  
Iris Löckener ◽  
Sarah M. Essert ◽  
Esther Sib ◽  
Gabriele Bierbaum ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Sewage Treatment ◽  
Sewage Treatment Plant ◽  
Treatment Plant ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
River Rhine ◽  
Antibiotic Resistant Bacteria ◽  
Surrounding Water ◽  
Antibiotic Resistant

Bacterial infections have been treated effectively by antibiotics since the discovery of penicillin in 1928. A worldwide increase in the use of antibiotics led to the emergence of antibiotic resistant strains in almost all bacterial pathogens, which complicates the treatment of infectious diseases. Antibiotic-resistant bacteria play an important role in increasing the risk associated with the usage of surface waters (e.g., irrigation, recreation) and the spread of the resistance genes. Many studies show that important pathogenic antibiotic-resistant bacteria can enter the environment by the discharge of sewage treatment plants and combined sewage overflow events. Mussels have successfully been used as bio-indicators of heavy metals, chemicals and parasites; they may also be efficient bio-indicators for viruses and bacteria. In this study an influence of the discharge of a sewage treatment plant could be shown in regard to the presence of E. coli in higher concentrations in the mussels downstream the treatment plant. Antibiotic-resistant bacteria, resistant against one or two classes of antibiotics and relevance for human health could be detected in the mussels at different sampling sites of the river Rhine. No multidrug-resistant bacteria could be isolated from the mussels, although they were found in samples of the surrounding water body.

scholarly journals The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 650
Author(s):  
Kylen E. Ridyard ◽  
Joerg Overhage
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Properties ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Peptide Antibiotic ◽  
Adaptive Responses ◽  
Antibiotic Resistant ◽  
Structural Modifications ◽  
Immobilization Techniques ◽  
Conventional Antibiotics

The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been considered as a potential alternative to conventional antibiotics as it displays broad spectrum antibacterial and anti-biofilm activities as well as immunomodulatory functions. While LL-37 has shown promising results, it has yet to receive regulatory approval as a peptide antibiotic. Despite the strong antimicrobial properties, LL-37 has several limitations including high cost, lower activity in physiological environments, susceptibility to proteolytic degradation, and high toxicity to human cells. This review will discuss the challenges associated with making LL-37 into a viable antibiotic treatment option, with a focus on antimicrobial resistance and cross-resistance as well as adaptive responses to sub-inhibitory concentrations of the peptide. The possible methods to overcome these challenges, including immobilization techniques, LL-37 delivery systems, the development of LL-37 derivatives, and synergistic combinations will also be considered. Herein, we describe how combination therapy and structural modifications to the sequence, helicity, hydrophobicity, charge, and configuration of LL-37 could optimize the antimicrobial and anti-biofilm activities of LL-37 for future clinical use.

scholarly journals Phage-Encoded Endolysins

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 124
Author(s):  
Fatma Abdelrahman ◽  
Maheswaran Easwaran ◽  
Oluwasegun I. Daramola ◽  
Samar Ragab ◽  
Stephanie Lynch ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Wall ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Therapeutic Strategies ◽  
Therapeutic Application ◽  
Significant Evidence ◽  
Crucial Information

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.

scholarly journals Susceptibility of Virulent Yersinia pestis Bacteria to Predator Bacteria in the Lungs of Mice

2018 ◽  
Vol 7 (1) ◽  
pp. 2 ◽  
Author(s):  
Riccardo Russo ◽  
Irina Kolesnikova ◽  
Thomas Kim ◽  
Shilpi Gupta ◽  
Androulla Pericleous ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Bacterial Infections ◽  
Treatment Modalities ◽  
The Novel ◽  
Global Public Health ◽  
Antibiotic Resistant ◽  
Colony Forming Units ◽  
Tier 1 ◽  
Predatory Bacteria ◽  
Lethal Doses

Multi-drug resistant bacterial infections are a serious threat to global public health. Changes in treatment modalities and prudent use of antibiotics can assist in reducing the threat, but new approaches are also required for untreatable cases. The use of predatory bacteria, such as Bdellovibrio bacteriovorus, is among the novel approaches being considered as possible therapeutics for antibiotic resistant and/or unidentified bacterial infections. Previous studies have examined the feasibility of using predatory bacteria to reduce colony-forming units (CFUs) in the lungs of rats exposed to lethal doses of Klebsiella pneumoniae; here we apply the approach to the Tier 1 select agent Yersinia pestis, and show that three doses of B. bacteriovorus introduced every six hours reduces the number of CFUs of Y. pestis in the lungs of inoculated mice by 86% after 24 h of infection. These experiments further demonstrate that predatory bacteria may serve to combat Gram negative bacterial infections, including those considered potential bioweapon agents, in the future.

scholarly journals Increase in Antibiotic-Resistant Gram-Negative Bacterial Infections in Febrile Neutropenic Children

2016 ◽  
Vol 48 (3) ◽  
pp. 181 ◽  
Author(s):  
Joon Hee Lee ◽  
Seul-Ki Kim ◽  
Seong Koo Kim ◽  
Seung Beom Han ◽  
Jae Wook Lee ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Antibiotic Resistant ◽  
Gram Negative

scholarly journals Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Author(s):  
Ayman El-Shibiny ◽  
Salma El-Sahhar
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Clinical Applications ◽  
Western World ◽  
Resistant Bacteria ◽  
Vaccine Production ◽  
Bacterial Populations ◽  
Antibiotic Resistant

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.

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