Peptide-Like Nylon-3 Polymers with Activity against Phylogenetically Diverse, Intrinsically Drug-Resistant Pathogenic Fungi

Rank, Leslie A.; Walsh, Naomi M.; Lim, Fang Yun; Gellman, Samuel H.; Keller, Nancy P.; Hull, Christina M.

doi:10.1128/msphere.00223-18

Cited by 10 publications

(6 citation statements)

References 46 publications

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“…Nylon-3 copolymers or poly-β-peptides are a family of synthetic peptide-like polymers based on the structural moiety of AMPs and are made via anionic ring-opening polymerisation of β-lactams (Yang et al, 2011). The resulting polymers (MM-TM, DM-TM, and NM) display improved potency against a diverse range of fungal species including C. albicans, C. krusei, C. auris, C. neoformans, C. amylolentus and A. fumigatus with improved fungal selectivity over mammalian cells (Liu et al, 2013;Liu et al, 2014;Rank et al, 2018). The most effective nylon-3 polymer was found to be poly-βNM, composed of the cationic subunit βNM and the hydrophobic subunit CH in differing proportions.…”

Section: Synthetic Antimicrobial Peptide-like Polymers With Antifungal Activitymentioning

confidence: 99%

Antifungal Polymeric Materials and Nanocomposites

Ntow-Boahene

Cook²,

Good

2021

Front. Bioeng. Biotechnol.

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Rising global populations due to medicinal advancements increases the patient population susceptible to superficial and severe fungal infections. Fungi often implicated in these diseases includes the dermatophytes (Microsporum spp., Epidermophtyon spp., Trichophyton spp.) as well as species of the Candida spp., Aspergillosis spp. and Cryptococcus spp. genera. In addition, increasing global populations leads to increasing agricultural demands. Thus, fungal infections of preharvested crops and stored food by plant pathogens such as Magnaporthe oryzae and Fusarium oxysporum can have detrimental socioeconomic effects due to food insecurity. Current antifungal strategies are based mainly on small molecule antifungal drugs. However, these drugs are limited by poor solubility and bioavailability. Furthermore, antifungal resistance against these drugs are on the rise. Thus, antimicrobial polymers offer an alternative antifungal strategy. Antifungal polymers are characterised by cationic and hydrophobic regions where the cationic regions have been shown to interact with microbial phospholipids and membranes. These polymers can be synthetic or natural and demonstrate distinct antifungal mechanisms ranging from fungal cell membrane permeabilisation, cell membrane depolarisation or cell entry. Although the relative importance of such mechanisms is difficult to decipher. Due to the chemical properties of these polymers, they can be combined with other antimicrobial compounds including existing antifungal drugs, charcoals, lipids and metal ions to elicit synergistic effects. In some cases, antifungal polymers and nanocomposites show better antifungal effects or reduced toxicity compared to the widely used small molecule antifungal drugs. This review provides an overview of antimicrobial polymers and nanocomposites with antifungal activity and the current understanding of their antifungal mechanisms.

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Section: Synthetic Antimicrobial Peptide-like Polymers With Antifungal Activitymentioning

confidence: 99%

Antifungal Polymeric Materials and Nanocomposites

Ntow-Boahene

Cook²,

Good

2021

Front. Bioeng. Biotechnol.

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“…Nylon-3 polymers have been proven to have significant activity against pathogenic strains of C. albicans that are resistant to conventional medication. Particularly, nylon-3 polymers with β-amino residues (βNM) in their backbone structure attracted more interest due to their resemblance to proteins that induce biocompatibility [60][61][62][63]. Moreover, such nylon-3 polymers can be easily prepared, being promising as clinical antifungal agents [60].…”

Section: Polymeric Materialsmentioning

confidence: 99%

Biomaterials for the Prevention of Oral Candidiasis Development

et al. 2021

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Thousands of microorganisms coexist within the human microbiota. However, certain conditions can predispose the organism to the overgrowth of specific pathogens that further lead to opportunistic infections. One of the most common such imbalances in the normal oral flora is the excessive growth of Candida spp, which produces oral candidiasis. In immunocompromised individuals, this fungal infection can reach the systemic level and become life-threatening. Hence, prompt and efficient treatment must be administered. Traditional antifungal agents, such as polyenes, azoles, and echinocandins, may often result in severe adverse effects, regardless of the administration form. Therefore, novel treatments have to be developed and implemented in clinical practice. In this regard, the present paper focuses on the newest therapeutic options against oral Candida infections, reviewing compounds and biomaterials with inherent antifungal properties, improved materials for dental prostheses and denture adhesives, drug delivery systems, and combined approaches towards developing the optimum treatment.

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“…From these pioneering works, more studies emerged in which different nylon-3 derived copolymers were studied. On one of these studies, the evaluated nylon-3 derivative showed excellent antifungal activity against several organisms from the genera Candida and Cryptococcus, comparable to fluconazole and amphotericin B (AmB) (Rank et al, 2017(Rank et al, , 2018, even showing synergism when used along these antifungals. Unfortunately, these substrates were not effective against Aspergillus spp by themselves, but they were shown to enhance the effect of other azole antifungals such as posaconazole and itraconazole against these pathogens.…”

Section: A Final Series Of Examples Of Chitosan Modification Is the Workmentioning

confidence: 99%

“…Finally, for this work, the cytotoxicity of the compounds was evaluated and it was concluded that these compounds are still biocompatible up to doses much higher than the determined MICs (Rank et al, 2017). In a follow-up study, the same research group evaluated new derivatives of these compounds obtaining an extensive list of inhibition interactions within several genera of fungi (Rank et al, 2018).…”

Section: A Final Series Of Examples Of Chitosan Modification Is the Workmentioning

confidence: 99%

Antifungal polymers for medical applications

Velazco‐Medel¹,

Camacho‐Cruz²,

Lugo-González³

et al. 2020

Med Devices & Sens

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The application of polymers as medical devices has steadily increased in almost all medical fields because of the versatility of these materials. Thus, research has focused both on the development of more appropriate materials for specific situations and on the modification of already useful materials for the improvement of their intrinsic properties. Modifications on this kind of materials have increased their potential uses by adapting their mechanical properties to specific needs. Moreover, biocompatibility of the polymeric materials has been improved by the inclusion of certain functional groups, providing responses to physical and chemical stimuli present in physiological conditions.Until recently, one of the most worrying problems in hospitals has been infections derived from medical devices usage. Typically, this kind of infections was handled with the use of prophylactic and therapeutic treatments with 'classic' (low-molecular weight) antimicrobial agents. This strategy has been effective in most patients suffering from nosocomial infections. However, it has the disadvantage of substantially increasing the probability of antimicrobial-resistant pathogens appearance, which continue to be especially dangerous in hospital environments (Cohen et al., 2017; World Health Organization, n.d.;Zegers et al., 2017). Additionally, due to

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Peptide-Like Nylon-3 Polymers with Activity against Phylogenetically Diverse, Intrinsically Drug-Resistant Pathogenic Fungi

Cited by 10 publications

References 46 publications

Antifungal Polymeric Materials and Nanocomposites

Antifungal Polymeric Materials and Nanocomposites

Biomaterials for the Prevention of Oral Candidiasis Development

Antifungal polymers for medical applications

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