Antimicrobial and Antibiofilm Activity of UP-5, an Ultrashort Antimicrobial Peptide Designed Using Only Arginine and Biphenylalanine

Almaaytah, Ammar; Qaoud, Mohammed T; Mohammed, Gubran Khalil; Abualhaijaa, Ahmad; Knappe, Daniel; Hoffmann, Ralf; Al-Balas, Qosay

doi:10.3390/ph11010003

Cited by 40 publications

(36 citation statements)

References 71 publications

(80 reference statements)

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“…Many natural AMPs are in the range of 10 to 50 amino acids in length. The length of AMPs directly translates into production cost of AMPs in the development stage; hence, the discovery of ultrashort and/or truncated AMPs with less than five amino acids has been pursued . For instance, a synthetic tripeptide LTX‐109 ( 17 , Figure ) is derived from bovine lactoferricin, which corresponds to 17 to 31 lactoferrin fragment, FKCRRWQWRMKKLGA.…”

Section: Improvement Strategies Of Ampsmentioning

confidence: 99%

Antimicrobial peptides under clinical investigation

2019

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Overuse of conventional antibiotics as well as the slow pace of new antibiotic drug development leads to antimicrobial resistance (AMR). Because infections with multi‐drug resistant (MDR) pathogens have become a public health issue, the need for a novel class of antibiotics is urgent. Recently, antimicrobial peptides (AMPs) have emerged as a promising platform to fight against MDR bacteria ensuring broad‐spectrum antimicrobial activity and relatively low resistance emergence. Currently, a number of AMPs are undergoing clinical and preclinical trials against various infectious diseases. This review lists the 36 AMPs (27 clinical and 9 preclinical) with brief information about their origin, structure, mechanism, and development status. From the examples of AMPs under clinical investigation, we categorized several improvement strategies and highlighted directions for the future design of AMPs.

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Section: Improvement Strategies Of Ampsmentioning

confidence: 99%

Antimicrobial peptides under clinical investigation

2019

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“…Accordingly, there are many possible modifications ranging from the incorporation of unnatural amino acids (of which more than 700 are known [36]) and peptides with altered backbones, to entirely different chemical structures. These modifications and structural differences are often able to resolve stability and cytotoxicity issues [30,32,35]. Raman et al [30], for example, designed a β-peptide with anti-fungal and anti-biofilm activity against Candida albicans, which remained structurally stable and active in synthetic urine media.…”

Section: Design Of Anti-biofilm Peptidesmentioning

confidence: 99%

“…Raman et al [30], for example, designed a β-peptide with anti-fungal and anti-biofilm activity against Candida albicans, which remained structurally stable and active in synthetic urine media. A peptidomimetic of 5 residues containing only arginine and biphenylalanine also showed anti-biofilm activity against multiple Gram-negative and Gram-positive bacteria, and exhibited very low toxicity to human erythrocytes and Vero monkey kidney epithelial cells, purportedly due to its short size and low hydrophobicity [32]. Conversely one study showed that enantiomeric peptides with D amino acids tended to have potent activity while being protease resistant [16,17].…”

Section: Design Of Anti-biofilm Peptidesmentioning

confidence: 99%

“…Natural and synthetic anti-biofilm peptides are promising agents for the treatment of biofilm infections, with low-resistance profiles and broad spectrum activity against pre-formed biofilms [4,11]. These peptides can be designed to improve their anti-biofilm specificity and stability inside the host, while reducing cytotoxicity and aggregation [22,25,29,32,35]. Furthermore, peptide design has the potential to engineer peptide sequences and structures that can specifically target the regulatory mechanisms behind biofilm formation, such as ubiquitous secondary messengers that trigger adaptive responses to diverse disease-related niches [16,17,23].…”

Section: Future Perspectives For Discovery Design and Application Omentioning

confidence: 99%

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Design and Assessment of Anti-Biofilm Peptides: Steps Toward Clinical Application

Dostert¹,

Belanger²,

Hancock³

2018

J Innate Immun

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Highly antibiotic resistant, microbial communities, referred to as biofilms, cause various life-threatening infections in humans. At least two-thirds of all clinical infections are biofilm associated, and antibiotic therapy regularly fails to cure patients. Anti-biofilm peptides represent a promising approach to treat these infections by targeting biofilm-specific characteristics such as highly conserved regulatory mechanisms. They are being considered for clinical application and we discuss here key factors in discovery, design, and application, particularly the implementation of host-mimicking conditions, that are required to enable the successful advancement of potent anti-biofilm peptides from the bench to the clinic.

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“…Interpretation and assessment of the FIC indices were performed according to the broth microdilution checkerboard technique. 21 , 22 …”

Section: Methodsmentioning

confidence: 99%

Hybridization and antibiotic synergism as a tool for reducing the cytotoxicity of antimicrobial peptides

Almaaytah¹,

Qaoud²,

Abualhaijaa³

et al. 2018

IDR

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IntroductionAs the development of new antimicrobial agents faces a historical decline, the issue of bacterial drug resistance has become a serious dilemma that threatens the human population worldwide. Antimicrobial peptides (AMPs) represent an attractive and a promising class of antimicrobial agents.AimThe hybridization of AMPs aimed at merging two individual active fragments of native peptides to generate a new AMP with altered physicochemical properties that translate into an enhanced safety profile.Materials and methodsIn this study, we have rationally designed a new hybrid peptide via combining two individual α-helical fragments of both BMAP-27 and OP-145. The resultant peptide, was evaluated for its antimicrobial and antibiofilm activity against a range of microbial strains. The resultant peptide was also evaluated for its toxicity against mammalian cells using hemolytic and anti proliferative assays.ResultsThe antimicrobial activity of H4 revealed that the peptide is displaying a broad spectrum of activity against both Gram-positive and Gram-negative bacteria including standard and multidrug-resistant bacterial strains in the range of 2.5–25 μM. The new hybrid peptide displayed potent activity in eradicating biofilm-forming cells, and the reported minimum biofilm eradication concentrations were equal to the minimum inhibitory concentration values reported for planktonic cells. Additionally, H4 exhibited reduced toxicity profiles against eukaryotic cells. Combining H4 peptide with conventional antibiotics has led to a dramatic enhancement of the antimicrobial activity of both agents with synergistic or additive outcomes.ConclusionOverall, this study indicates the success of both the hybridization and synergism strategy in developing AMPs as potential antimicrobial therapeutics with reduced toxicity profiles that could be efficiently employed to eradicate resistant bacterial strains and enhance the selectivity and toxicity profiles of native AMPs.

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Antimicrobial and Antibiofilm Activity of UP-5, an Ultrashort Antimicrobial Peptide Designed Using Only Arginine and Biphenylalanine

Cited by 40 publications

References 71 publications

Antimicrobial peptides under clinical investigation

Antimicrobial peptides under clinical investigation

Design and Assessment of Anti-Biofilm Peptides: Steps Toward Clinical Application

Hybridization and antibiotic synergism as a tool for reducing the cytotoxicity of antimicrobial peptides

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