Systematic comparison of activity and mechanism of antimicrobial peptides against nosocomial pathogens

Lin, Bruce; Hung, Andrew; Li, Rong; Barlow, Anders J.; Singleton, William; Matthyssen, Tamara; Sani, Marc‐Antoine; Hossain, Mohammed Akhter; Wade, John D.; O'Brien-Simpson, Neil M; Li, Wenyi

doi:10.1016/j.ejmech.2022.114135

Cited by 28 publications

(32 citation statements)

References 50 publications

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“…It is also likely that T. pallidum encounters pathogenic / uropathogenic strains of E. coli during infection. Although these strains were not tested in our antimicrobial susceptibility assays, previous studies have shown that AMPs from other organisms exhibit similar levels of antimicrobial activity against both non-pathogenic and pathogenic / uropathogenic E. coli strains ( Fedders et al, 2010 ; Aghazadeh et al, 2019 ; Mardirossian et al, 2019 ; Moazzezy et al, 2020 ; Li et al, 2022 ; Lin et al, 2022 ). Tp0749_C also exhibited antimicrobial activity against the Gram-negative bacterium, P. aeruginosa .…”

Section: Discussionmentioning

confidence: 99%

Identification and Functional Characterization of Peptides With Antimicrobial Activity From the Syphilis Spirochete, Treponema pallidum

et al. 2022

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The etiological agent of syphilis, Treponema pallidum ssp. pallidum, is a highly invasive “stealth” pathogen that can evade the host immune response and persist within the host for decades. This obligate human pathogen is adept at establishing infection and surviving at sites within the host that have a multitude of competing microbes, sometimes including pathogens. One survival strategy employed by bacteria found at polymicrobial sites is elimination of competing microorganisms by production of antimicrobial peptides (AMPs). Antimicrobial peptides are low molecular weight proteins (miniproteins) that function directly via inhibition and killing of microbes and/or indirectly via modulation of the host immune response, which can facilitate immune evasion. In the current study, we used bioinformatics to show that approximately 7% of the T. pallidum proteome is comprised of miniproteins of 150 amino acids or less with unknown functions. To investigate the possibility that AMP production is an unrecognized defense strategy used by T. pallidum during infection, we developed a bioinformatics pipeline to analyze the complement of T. pallidum miniproteins of unknown function for the identification of potential AMPs. This analysis identified 45 T. pallidum AMP candidates; of these, Tp0451a and Tp0749 were subjected to further bioinformatic analyses to identify AMP critical core regions (AMPCCRs). Four potential AMPCCRs from the two predicted AMPs were identified and peptides corresponding to these AMPCCRs were experimentally confirmed to exhibit bacteriostatic and bactericidal activity against a panel of biologically relevant Gram-positive and Gram-negative bacteria. Immunomodulation assays performed under inflammatory conditions demonstrated that one of the AMPCCRs was also capable of differentially regulating expression of two pro-inflammatory chemokines [monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8)]. These findings demonstrate proof-of-concept for our developed AMP identification pipeline and are consistent with the novel concept that T. pallidum expresses AMPs to defend against competing microbes and modulate the host immune response.

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Section: Discussionmentioning

confidence: 99%

Identification and Functional Characterization of Peptides With Antimicrobial Activity From the Syphilis Spirochete, Treponema pallidum

et al. 2022

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“…The mechanisms of action of Pardaxin (1-22), MSI-78 (4-20), DMPC (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and Cecropin B (1-21), very promising AMPs against the most threatening MDR nosocomial bacterial pathogens, have been investigated recently [46]. The study showed that the first two peptides are the most active against the bacteria tested; they act mainly through the membrane damage and destruction.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Lights and Shadows on the Therapeutic Use of Antimicrobial Peptides

Bellotti

Remelli

2022

Molecules

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The emergence of antimicrobial-resistant infections is still a major concern for public health worldwide. The number of pathogenic microorganisms capable of resisting common therapeutic treatments are constantly increasing, highlighting the need of innovative and more effective drugs. This phenomenon is strictly connected to the rapid metabolism of microorganisms: due to the huge number of mutations that can occur in a relatively short time, a colony can “adapt” to the pharmacological treatment with the evolution of new resistant species. However, the shortage of available antimicrobial drugs in clinical use is also caused by the high costs involved in developing and marketing new drugs without an adequate guarantee of an economic return; therefore, the pharmaceutical companies have reduced their investments in this area. The use of antimicrobial peptides (AMPs) represents a promising strategy for the design of new therapeutic agents. AMPs act as immune defense mediators of the host organism and show a poor ability to induce antimicrobial resistance, coupled with other advantages such as a broad spectrum of activity, not excessive synthetic costs and low toxicity of both the peptide itself and its own metabolites. It is also important to underline that many antimicrobial peptides, due to their inclination to attack cell membranes, have additional biological activities, such as, for example, as anti-cancer drugs. Unfortunately, they usually undergo rapid degradation by proteolytic enzymes and are characterized by poor bioavailability, preventing their extensive clinical use and landing on the pharmaceutical market. This review is focused on the strength and weak points of antimicrobial peptides as therapeutic agents. We give an overview on the AMPs already employed in clinical practice, which are examples of successful strategies aimed at overcoming the main drawbacks of peptide-based drugs. The review deepens the most promising strategies to design modified antimicrobial peptides with higher proteolytic stability with the purpose of giving a comprehensive summary of the commonly employed approaches to evaluate and optimize the peptide potentialities.

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“…Action mechanism of AMPs is primarily membrane destabilization and disruption (Lin et al, 2022). The integrity of the bacterial membrane was examined in this study.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…Because the target of AMPs is bacterial cell membrane, which is different from the antibacterial mechanism of traditional antibiotics, they are expected to become the most promising new antibiotics in the post antibiotic era (Brogden, 2005;Mahlapuu et al, 2020;Li et al, 2021;Liu et al, 2021). AMPs primarily operated through membrane destabilization and disruption mechanisms, and different AMPs had the different effects on membrane integrity and phospholipid membrane interactions (Lin et al, 2022). Cell-penetrating peptides (CPPs) are commonly small cationic peptides that interact with membrane and frequently have amphiphilic properties (Ramsey et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Florfenicol-Polyarginine Conjugates Exhibit Promising Antibacterial Activity Against Resistant Strains

Yang

Qin

et al. 2022

Front. Chem.

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Florfenicol was widely used as antibiotic in the livestock and poultry breeding industry, resulting in a serious problem of drug resistance. In order to solve the resistance of florfenicol, this study designed and synthesized a new series of florfenicol-polyarginine conjugates and tested for antimicrobial activities. Drug-sensitive bacteria, gram-negative bacteria Escherichia coli (E. coli) and gram-positive Staphylococcus aureus (S. aureus), were sensitive to several of the compounds tested. These conjugates also showed excellent activity against drug-resistant strains such as methicillin-resistant S. aureus (MRSA) and florfenicol resistant Escherichia coli strains (2017XJ30, 2019XJ20), one of which as E6 had a minimum inhibitory concentration of 12.5 μmol/L. These conjugates did not allow bacteria to develop resistance and also decreased bacterial growth by membrane depolarization and disruption. Additionally, florfenicol succinate (C1) showed certain activity after coupling with arginine. This suggested that conjugating arginine to florfenicol succinate effectively modulated the properties of prodrugs. These new conjugates may provide useful insights for expanding the pool of antibiotics.

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Systematic comparison of activity and mechanism of antimicrobial peptides against nosocomial pathogens

Cited by 28 publications

References 50 publications

Identification and Functional Characterization of Peptides With Antimicrobial Activity From the Syphilis Spirochete, Treponema pallidum

Identification and Functional Characterization of Peptides With Antimicrobial Activity From the Syphilis Spirochete, Treponema pallidum

Lights and Shadows on the Therapeutic Use of Antimicrobial Peptides

Florfenicol-Polyarginine Conjugates Exhibit Promising Antibacterial Activity Against Resistant Strains

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