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Antimicrobial peptide polymers: no escape to ESKAPE pathogens-a review.

ABSTRACT: Antimicrobial resistance (AMR) is one of the significant clinical challenges and also an emerging area of concern arising from nosocomial infections of ESKAPE pathogens, which has been on the rise in both the developed and developing countries alike. These pathogens/superbugs can undergo rapid mutagenesis, which helps them to generate resistance against antimicrobials in addition to the patient's non-adherence to the antibiotic regimen. Sticking to the idea of a 'one-size-fits-all' approach has led to the inappropriate administration of antibiotics resulting in augmentation of antimicrobial resistance. Antimicrobial peptides (AMPs) are the natural host defense peptides that have gained attention in the field of AMR, and recently, synthetic AMPs are well studied to overcome the drawbacks of natural counterparts. This review deals with the novel techniques utilizing the bacteriolytic activity of natural AMPs. The effective localization of these peptides onto the negatively charged bacterial surface by using nanocarriers and structurally nanoengineered antimicrobial peptide polymers (SNAPPs) owing to its smaller size and better antimicrobial activity is also described here.

SUBMITTER: Mukhopadhyay S

PROVIDER: S-EPMC7395033 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Antimicrobial peptide polymers: no escape to ESKAPE pathogens-a review.

Mukhopadhyay Songhita S Bharath Prasad A S AS Mehta Chetan H CH Nayak Usha Y UY

World journal of microbiology & biotechnology 20200801 9

Antimicrobial resistance (AMR) is one of the significant clinical challenges and also an emerging area of concern arising from nosocomial infections of ESKAPE pathogens, which has been on the rise in both the developed and developing countries alike. These pathogens/superbugs can undergo rapid mutagenesis, which helps them to generate resistance against antimicrobials in addition to the patient's non-adherence to the antibiotic regimen. Sticking to the idea of a 'one-size-fits-all' approach has ...[more]

PMID: 32737599

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Project description:ESKAPE bacteria are a major cause of multidrug-resistant infections, and new drugs are urgently needed to combat these pathogens. Given the importance of iron in bacterial physiology and pathogenicity, iron uptake and metabolism have become attractive targets for the development of new antibacterial drugs. In this scenario, the FDA-approved iron mimetic metal Gallium [Ga(III)] has been successfully repurposed as an antimicrobial drug. Ga(III) disrupts ferric iron-dependent metabolic pathways, thereby inhibiting microbial growth. This work provides the first comparative assessment of the antibacterial activity of Ga(NO3)3 (GaN), Ga(III)-maltolate (GaM), and Ga(III)-protoporphyrin IX (GaPPIX), belonging to the first-, second- and third-generation of Ga(III) formulations, respectively, on ESKAPE species, including reference strains and multidrug-resistant (MDR) clinical isolates. In addition to the standard culture medium Mueller Hinton broth (MHB), iron-depleted MHB (DMHB) and RPMI-1640 supplemented with 10% human serum (HS) (RPMI-HS) were also included in Ga(III)-susceptibility tests, because of their different nutrient and iron contents. All ESKAPE species were resistant to all Ga(III) compounds in MHB and DMHB (MIC > 32 μM), except Staphylococcus aureus and Acinetobacter baumannii, which were susceptible to GaPPIX. Conversely, the antibacterial activity of GaN and GaM was very evident in RPMI-HS, in which the low iron content and the presence of HS better mimic the in vivo environment. In RPMI-HS about 50% of the strains were sensitive (MIC < 32) to GaN and GaM, both compounds showing a similar spectrum of activity, although GaM was more effective than GaN. In contrast, GaPPIX lost its antibacterial activity in RPMI-HS likely due to the presence of albumin, which binds GaPPIX and counteracts its inhibitory effect. We also demonstrated that the presence of multiple heme-uptake systems strongly influences GaPPIX susceptibility in A. baumannii. Interestingly, GaN and GaM showed only a bacteriostatic effect, whereas GaPPIX exerted a bactericidal activity on susceptible strains. Altogether, our findings raise hope for the future development of Ga(III)-based compounds in the treatment of infections caused by multidrug-resistant ESKAPE pathogens.

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Antimicrobial peptide polymers: no escape to ESKAPE pathogens-a review.

Publications

Antimicrobial peptide polymers: no escape to ESKAPE pathogens-a review.

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