Abstract
Antimicrobial resistance is becoming one the most serious health threats worldwide, as it not only hampers effective treatment of infectious diseases using current antibiotics, but also increases the risks of medical procedures like surgery, transplantation, bone and dental implantation, chemotherapy, or chronic wound management. To date, there are no effective measures to tackle life-threatening nosocomial infections caused by multidrug resistant bacterial species, of which Gram-negative species within the so-called “ESKAPE” pathogens are the most worrisome. Many such bacteria are frequently isolated from severely infected skin lesions such as diabetic foot ulcers (DFU). In this connection, we are pursuing new peptide constructs encompassing antimicrobial and collagenesis-inducing motifs, to tackle skin and soft tissue infections by exerting a dual effect: antimicrobial protection and faster healing of the wound. This produced peptide 3.1-PP4 showed MIC values as low as 1.0 and 2.1 μM against Escherichia coli and Pseudomonas aeruginosa, respectively, and low toxicity to HFF-1 human fibroblasts. Remarkably, the peptide was also potent against multidrug-resistant isolates of Klebsiella pneumoniae, E. coli, and P. aeruginosa (MIC values between 0.5 and 4.1 μM), and hampered the formation of/disaggregated K. pneumoniae biofilms of resistant clinical isolates. Moreover, this notable hybrid peptide retained the collagenesis-inducing behavior of the reference cosmeceutical peptide C16-PP4 (“Matrixyl”). In conclusion, 3.1-PP4 is a highly promising lead toward development of a topical treatment for severely infected skin injuries.
Highlights
According to the World Health Organization (WHO), antimicrobial resistance is currently disseminated worldwide and can affect anyone, regardless of age, health and socio-economic status (WHO, 2014)
Since several antimicrobial peptides (AMPs) have been reported as efficient antibiofilm agents (Yasir et al, 2018; Haney et al, 2019), we have further investigated whether peptide 3.1-PP4 would display antibiofilm activity
The present disclosure of hybrid peptide constructs combining the wide spectrum antimicrobial peptide 3.1 and the collagenesisinducing peptide PP4 is unprecedented, and results reported demonstrate the potential that such hybrids enclose for the future development of new potent antibacterial agents that are collagenesis inducers
Summary
According to the World Health Organization (WHO), antimicrobial resistance is currently disseminated worldwide and can affect anyone, regardless of age, health and socio-economic status (WHO, 2014). CSSTI are a mounting burden to both patients and healthcare due to growth of life expectancy: for instance, according to the European Wound Management Association (EWMA, 2014), about 2% of the population in developed countries suffers from chronic wounds, being estimated that 25–50% of hospital beds are occupied by patients with such non-healing injuries, with average costs adding up to 2–4% of the total European budget for healthcare; in the US, the Center for Disease Control estimates that about 50–70% of the 2 million reported HAI are associated to implants or catheters, with mortality rates ranging from 25% for mechanical heart valves (VanEpps and Younger, 2016)
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