Enhanced biofilm prevention activity of a SPLUNC1-derived antimicrobial peptide against Staphylococcus aureus

Yu, Zhongjie; Deslouches, Berthony; Walton, William G.; Redinbo, Matthew R.; Di, Y. Peter

doi:10.1371/journal.pone.0203621

Cited by 8 publications

(9 citation statements)

References 47 publications

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“…Furthermore, some of the AMPs have the potential to work as anti-biofilm agents with high clinical value. 52 , 54 , 55 In general, AMPs have a promising prospect in the treatment of chronic wound infection.…”

Section: Therapeutic Strategies Of Chronic Wound Infectionmentioning

confidence: 99%

Therapeutic strategies for chronic wound infection

Liu¹,

Ni²,

Huang³

et al. 2022

Chinese Journal of Traumatology

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s Chronic wounds have always been a tough fight in clinical practice, which can not only make patients suffer from pain physically and mentally but also impose a heavy burden on the society. More than one factor is relevant to each step of the development of chronic wounds. Along with the in-depth research, we have realized that figuring out the pathophysiological mechanism of chronic wounds is the foundation of treatment, while wound infection is the key point concerned. The cause of infection should be identified and prevented promptly once diagnosed. This paper mainly describes the mechanism, diagnosis and therapeutic strategies of chronic wound infection, and will put an emphasis on the principle of debridement.

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Section: Therapeutic Strategies Of Chronic Wound Infectionmentioning

confidence: 99%

Therapeutic strategies for chronic wound infection

Liu¹,

Ni²,

Huang³

et al. 2022

Chinese Journal of Traumatology

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“…We previously demonstrated the antibiofilm activity of α4 and α4-M1 (both 30 residues long) against S. aureus, and these two AMPs displayed no toxicity to red blood cells (RBC) and white blood cells (WBC) (22). In this study, the goal was to determine whether these peptides (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Our group has been focusing on addressing this limitation, as demonstrated by the efficacy of engineered AMPs such as WLBU2 and natural AMPs, including frog skin-derived esculentin systemically and via direct delivery in the mouse airway (12, 23, 24, 31, 57, 58). Nevertheless, the increased host toxicity resulting from these optimization studies led us to adopt a natural template alternative, which facilitates the successful optimization of α4-short without the cytotoxicity observed in highly optimized de novo -engineered AMPs (22). The enhanced in vivo efficacy appears to be based on structural optimization of AMPs partly using Trp content.…”

Section: Discussionmentioning

confidence: 99%

“…One particular motif of the SPLUNC1 secondary structure that is 30 residues long, α4 (13), displays a helical structure (13, 18). We previously showed that the synthetic α4 region displayed modest antibiofilm property (22), which could be enhanced by optimization of the cationic amphipathic structure reminiscent of that of well-known natural AMPs (23–26). In this study, we sought to explore the potential of α4-derived antimicrobial peptides (α4-AMPs) to display broad-spectrum bactericidal and antibiofilm activities against the most common MDR pathogens.…”

Section: Introductionmentioning

confidence: 99%

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Antibacterial Properties and Efficacy of a Novel SPLUNC1-Derived Antimicrobial Peptide, α4-Short, in a Murine Model of Respiratory Infection

Jiang

Deslouches

Chen

et al. 2019

mBio

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Multidrug resistance (MDR) by bacterial pathogens constitutes a global health crisis, and resistance to treatment displayed by biofilm-associated infections (e.g., cystic fibrosis, surgical sites, and medical implants) only exacerbates a problem that is already difficult to overcome. Antimicrobial peptides (AMPs) are a promising class of therapeutics that may be useful in the battle against antibiotic resistance, although certain limitations have hindered their clinical development. The goal of this study was to examine the therapeutic potential of novel AMPs derived from the multifunctional respiratory host defense protein SPLUNC1. Using standard growth inhibition and antibiofilm assays, we demonstrated that a novel structurally optimized AMP, α4-short, was highly effective against the most common group of MDR bacteria while showing broad-spectrum bactericidal and antibiofilm activities. With negligible hemolysis and toxicity to white blood cells, the new peptide also demonstrated in vivo efficacy when delivered directly into the airway in a murine model of Pseudomonas aeruginosa-induced respiratory infection. The data warrant further exploration of SPLUNC1-derived AMPs with optimized structures to assess the potential application to difficult-to-cure biofilm-associated infections. IMPORTANCE The rise of superbugs underscores the urgent need for novel antimicrobial agents. Antimicrobial peptides (AMPs) have the ability to kill superbugs regardless of resistance to traditional antibiotics. However, AMPs often display a lack of efficacy in vivo. Sequence optimization and engineering are promising but may result in increased host toxicity. We report here the optimization of a novel AMP (α4-short) derived from the multifunctional respiratory protein SPLUNC1. The AMP α4-short demonstrated broad-spectrum activity against superbugs as well as in vivo efficacy in the P. aeruginosa pneumonia model. Further exploration for clinical development is warranted.

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“…A microtiter plate assay was performed, as previously described. − Briefly, log-phase bacteria were diluted in Dulbecco’s modified Eagle’s medium (DMEM, instead of rich broth to facilitate biofilm growth) to 10 8 CFU/mL based on predetermined bacterial numbers that correlate with optical density (OD), using a spectrophotometer. A 50 μL volume of control or UBM (in PBS), at different concentrations, was added to 50 μL of bacterial suspension in a sterile 96-well polystyrene plate (Fisher Scientific, Pittsburgh, PA).…”

Section: Methodsmentioning

confidence: 99%

Treatment with a Urinary Bladder Matrix Alters the Innate Host Response to Pneumonia Induced by Escherichia coli

Lin

Zhu

Yang

et al. 2021

ACS Biomater. Sci. Eng.

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Escherichia coli has become the prominent cause of nosocomial pneumonia in recent years. In the meantime, some strains of E. coli have developed resistance to commonly used antibacterial drugs. The urinary bladder matrix (UBM) is a biologically derived scaffold material that has been used to promote site-appropriate tissue remodeling in a variety of body systems, partially through the modulation of the innate immune response. In this study, we seek to determine UBM efficacy in preventing bacterial pneumonia in mouse lungs using the Gram-negative bacterial strain E. coli. Our results show that the UBM prevented bacterial biofilm formation in both abiotic and biotic conditions through experimentation on polystyrene plates and culture on the apical surface of differentiated airway epithelial cells. Intratracheal treatment with UBM led to host protection from E. coli-induced respiratory infection in a murine pneumonia model. Transcriptomic analysis revealed the involvement of the enhanced host immune response in UBM-treated mice. Additionally, UBM-treated macrophages had an increased iNOS expression and enhanced phagocytosis activity. Therefore, the protection against E. coli-induced infection and the antibacterial function observed by UBM is potentially through both the anti-biofilm activity and enhanced host immunity following UBM treatment. Taken together, our results support further investigation of UBM as an alternative treatment to attenuate bacterial-induced respiratory infection.

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Enhanced biofilm prevention activity of a SPLUNC1-derived antimicrobial peptide against Staphylococcus aureus

Cited by 8 publications

References 47 publications

Therapeutic strategies for chronic wound infection

Therapeutic strategies for chronic wound infection

Antibacterial Properties and Efficacy of a Novel SPLUNC1-Derived Antimicrobial Peptide, α4-Short, in a Murine Model of Respiratory Infection

Treatment with a Urinary Bladder Matrix Alters the Innate Host Response to Pneumonia Induced by Escherichia coli

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