The Membranotropic Peptide gH625 to Combat Mixed Candida albicans/Klebsiella pneumoniae Biofilm: Correlation between In Vitro Anti-Biofilm Activity and In Vivo Antimicrobial Protection

Maione, Angela; Alteriis, Elisabetta de; Carraturo, Federica; Galdiero, Stefania; Falanga, Annarita; Guida, Marco; Cosmo, Anna Di; Maselli, Valeria; Galdiero, Emilia

doi:10.3390/jof7010026

Cited by 29 publications

(17 citation statements)

References 31 publications

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“…mellonella larvae were selected to be absent of dark spots and similar in size (approximately 250-300 mg each). Each group containing 20 randomly chosen larvae was used for every treatment as previously reported [42]. Larvae were cleaned by an alcohol swab before injection.…”

Section: Determination Of In Vivo Antifungal Effects Using the G Mell...mentioning

confidence: 99%

WMR Peptide as Antifungal and Antibiofilm against Albicans and Non-Albicans Candida Species: Shreds of Evidence on the Mechanism of Action

Maione

Bellavita

Alteriis

et al. 2022

IJMS

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Candida species are the most common fungal pathogens infecting humans and can cause severe illnesses in immunocompromised individuals. The increased resistance of Candida to traditional antifungal drugs represents a great challenge in clinical settings. Therefore, novel approaches to overcome antifungal resistance are desired. Here, we investigated the use of an antimicrobial peptide WMR against Candida albicans and non-albicans Candida species in vitro and in vivo. Results showed a WMR antifungal activity on all Candida planktonic cells at concentrations between 25 μM to >50 μM and exhibited activity at sub-MIC concentrations to inhibit biofilm formation and eradicate mature biofilm. Furthermore, in vitro antifungal effects of WMR were confirmed in vivo as demonstrated by a prolonged survival rate of larvae infected by Candida species when the peptide was administered before or after infection. Additional experiments to unravel the antifungal mechanism were performed on C. albicans and C. parapsilosis. The time-killing curves showed their antifungal activity, which was further confirmed by the induced intracellular and mitochondrial reactive oxygen species accumulation; WMR significantly suppressed drug efflux, down-regulating the drug transporter encoding genes CDR1. Moreover, the ability of WMR to penetrate within the cells was demonstrated by confocal laser scanning microscopy. These findings provide novel insights for the antifungal mechanism of WMR against Candida albicans and non-albicans, providing fascinating scenarios for the identification of new potential antifungal targets.

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Section: Determination Of In Vivo Antifungal Effects Using the G Mell...mentioning

confidence: 99%

WMR Peptide as Antifungal and Antibiofilm against Albicans and Non-Albicans Candida Species: Shreds of Evidence on the Mechanism of Action

Maione

Bellavita

Alteriis

et al. 2022

IJMS

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“…The antimicrobial activity of natural peptides can be enhanced by various modifications to form synthetic peptides. Three such synthetic peptides have recently been demonstrated to be effective against C. albicans-S. aureus and C. albicans-K. pneumoniae biofilms in vitro and in mice and G. mellonella infections (Gupta et al, 2019;Galdiero et al, 2021a;Maione et al, 2021). Peptoids are peptide-mimics with increased resistance to proteases and therefore better stability in vivo (Luo et al, 2017).…”

Section: In Search Of Novel Therapeutic Solutions To Polymicrobial Bi...mentioning

confidence: 99%

Recent Advances and Opportunities in the Study of Candida albicans Polymicrobial Biofilms

Pohl

2022

Front. Cell. Infect. Microbiol.

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It is well known that the opportunistic pathogenic yeast, Candida albicans, can form polymicrobial biofilms with a variety of bacteria, both in vitro and in vivo, and that these polymicrobial biofilms can impact the course and management of disease. Although specific interactions are often described as either synergistic or antagonistic, this may be an oversimplification. Polymicrobial biofilms are complex two-way interacting communities, regulated by inter-domain (inter-kingdom) signaling and various molecular mechanisms. This review article will highlight advances over the last six years (2016-2021) regarding the unique biology of polymicrobial biofilms formed by C. albicans and bacteria, including regulation of their formation. In addition, some of the consequences of these interactions, such as the influence of co-existence on antimicrobial susceptibility and virulence, will be discussed. Since the aim of this knowledge is to inform possible alternative treatment options, recent studies on the discovery of novel anti-biofilm compounds will also be included. Throughout, an attempt will be made to identify ongoing challenges in this area.

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“…The G. mellonella microorganism infection model was used to evaluate the antimicrobial effect of WMR-4 in vivo, and a survival assay was performed as described previously [ 76 , 77 ]. Briefly, to test toxicity of WMR-4, larvae were treated with different concentrations (5, 10, 15, and 20 µM) of peptide, and survival was monitored every 24 h for a duration of 4 days.…”

Section: Methodsmentioning

confidence: 99%

Myxinidin-Derived Peptide against Biofilms Caused by Cystic Fibrosis Emerging Pathogens

Bellavita

Maione

Braccia

et al. 2023

IJMS

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Chronic lung infections in cystic fibrosis (CF) patients are triggered by multidrug-resistant bacteria such as Pseudomonas aeruginosa, Achromobacter xylosoxidans, and Stenotrophomonas maltophilia. The CF airways are considered ideal sites for the colonization and growth of bacteria and fungi that favor the formation of mixed biofilms that are difficult to treat. The inefficacy of traditional antibiotics reinforces the need to find novel molecules able to fight these chronic infections. Antimicrobial peptides (AMPs) represent a promising alternative for their antimicrobial, anti-inflammatory, and immunomodulatory activities. We developed a more serum-stable version of the peptide WMR (WMR-4) and investigated its ability to inhibit and eradicate C. albicans, S. maltophilia, and A. xylosoxidans biofilms in both in vitro and in vivo studies. Our results suggest that the peptide is able better to inhibit than to eradicate both mono and dual-species biofilms, which is further confirmed by the downregulation of some genes involved in biofilm formation or in quorum-sensing signaling. Biophysical data help to elucidate its mode of action, showing a strong interaction of WMR-4 with lipopolysaccharide (LPS) and its insertion in liposomes mimicking Gram-negative and Candida membranes. Our results support the promising therapeutic application of AMPs in the treatment of mono- and dual-species biofilms during chronic infections in CF patients.

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The Membranotropic Peptide gH625 to Combat Mixed Candida albicans/Klebsiella pneumoniae Biofilm: Correlation between In Vitro Anti-Biofilm Activity and In Vivo Antimicrobial Protection

Cited by 29 publications

References 31 publications

WMR Peptide as Antifungal and Antibiofilm against Albicans and Non-Albicans Candida Species: Shreds of Evidence on the Mechanism of Action

WMR Peptide as Antifungal and Antibiofilm against Albicans and Non-Albicans Candida Species: Shreds of Evidence on the Mechanism of Action

Recent Advances and Opportunities in the Study of Candida albicans Polymicrobial Biofilms

Myxinidin-Derived Peptide against Biofilms Caused by Cystic Fibrosis Emerging Pathogens

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