Development of Bactericidal Peptides against Multidrug-Resistant Acinetobacter baumannii with Enhanced Stability and Low Toxicity

Abstract

Pathogenic superbugs are the root cause of untreatable complex infections with limited or no treatment options. These infections are becoming more common as clinical antibiotics have lost their effectiveness over time. Therefore, the development of novel antibacterial agents is urgently needed to counter these microbes. Antimicrobial peptides (AMPs) are a viable treatment option due to their bactericidal potency against multiple microbial classes. AMPs are naturally selected physiological microbicidal agents that are found in all forms of organisms. In the present study, we developed two tilapia piscidin 2 (TP2)-based AMPs for antimicrobial application. Unlike the parent peptide, the redesigned peptides showed significant antimicrobial activity against multidrug-resistant bacterial species. These peptides also showed minimal cytotoxicity. In addition, they were significantly active in the presence of physiological salts, 50% human serum and elevated temperature. The designed peptides also showed synergistic activity when combined with clinical antibiotics. The current approach demonstrates a fruitful strategy for developing potential AMPs for antimicrobial application. Such AMPs have potential for progression to further trials and drug development investigations.

Investigations on the Wound Healing Potential of Tilapia Piscidin (TP)2-5 and TP2-6

“…The activation of dermal fibroblasts plays an important role in the skin reparative process [ 24 ]. TP2-5- and TP2-6-treated skin fibroblasts (CCD-966SK cells) caused significant LDH release at 31.25 and 125 μg/mL, respectively [ 20 ]. However, low concentrations of TP2-5 and TP2-6, ranging from 1.95 to 7.81 μg/mL, significantly promoted cell proliferation after 72 h incubation ( Figure 3 A).…”

“…Antimicrobial peptides (AMPs) are natural antibiotics recognized for their potent antibacterial and wound healing properties [ 13 , 30 ]. Recently, we developed two novel piscidin-like peptides, TP2-5 and TP2-6, which possess antibacterial and anti-biofilm activities against broad-spectrum bacteria [ 20 ]. In this study, we demonstrate that TP2-5 and TP2-6 promote wound healing processes in various types of skin cells, including keratinocytes, fibroblasts, and endothelial cells, along with low cytotoxic effects.…”

“…It has been found that collagen deposition is impaired in diabetic wounds due to decreased fibroblast proliferation and migration [ 45 , 46 ]. Here, we observed that TP2-5 and TP2-6 not only promote cell proliferation and migration, but they also stimulate the expression of collagen I and III in fibroblasts [ 20 ] ( Figure 3 ). Furthermore, previous studies have reported a double paracrine network in which the KGF secreted from fibroblasts promotes keratinocyte proliferation and migration, and stimulates the keratinocyte secretion of TGF-β1 [ 25 ].…”

“…Our previous report showed that TP2-5 and TP2-6 exert effective antimicrobial and antibiofilm activities against Acinetobacter baumannii ( A. baumannii ), even multidrug-resistant strains [ 20 ]. A. baumannii is a major cause of wound infections in patients who are critically ill, and its presence delays wound healing and promotes the development of sepsis [ 57 , 58 ].…”

“…To overcome such issues, we recently developed two peptides derived from the sequence of TP2, called TP2-5 and 2-6. The redesigned peptides exhibit effective antimicrobial and anti-biofilm activities with improved hemolytic activity and cytotoxic profiles [ 20 ]. These features suggest that TP2-5 and TP2-6 could be suitable for development as antimicrobial agents.…”