Hybrid Antimicrobial Peptide Targeting Staphylococcus aureus and Displaying Anti-infective Activity in a Murine Model

Abstract

Broad-spectrum antimicrobial peptides (AMPs) kill bacteria indiscriminately, increasing the possibility of an ecological imbalance in the microbiota. To solve this problem, new types of AMPs, which kill pathogenic bacteria without breaking the micro-ecological balance of the body, were proposed. Here, we successfully designed a targeting AMP, S2, which is a fusion peptide composed of a species-specific targeting domain and broad-spectrum AMP domain. In the current study, S2 showed specific killing activity against Staphylococcus aureus, and almost no resistance induced compared to penicillin. Mechanism studies indicated that S2 killed S. aureus by destroying the bacterial membrane. Meanwhile, S2 possessed excellent salt-tolerance properties and biocompatibility. Importantly, S2 exhibited perfect treatment efficacy against an S. aureus subcutaneous infection model and remained nontoxic. In conclusion, this study provides a promising strategy for designing specific AMPs against growing bacterial infections.

Rational Designed Hybrid Peptides Show up to a 6-fold Increase in Antimicrobial Activity and Demonstrate Different Ultrastructural Changes as the Parental Peptides measured by BioSAXS

“…Based on the success of the hybridization strategy reported by others, for example (Fox et al, 2012;Shang et al, 2020;Wade et al, 2018Wade et al, , 2019Xu et al, 2014), we hypothesized that hybrid molecules from two different classes of AMPs, which we have identified in the past as potential antimicrobial drug candidates, may lead to a further improvement of antimicrobial activity. Thus we combined the excellent activity of proline-rich and arginine-isoleucine-rich AMPs.…”

“…The peptide optP7 was used as a lead and selected for studying lipidation, glycosylation, cyclisation, and grafting into a cyclotide (Grimsey et al, 2020;Koehbach et al, 2021). Hybridization of different AMPs has been investigated to further improve their performance (Shang et al, 2020;Wade et al, 2018Wade et al, , 2019. Here we report the creation of different hybrid molecules using peptides optP1 (KIILRIRWR) and optP7 (KRRVWIIW) in combination with the Bac5(1-17) variant 291 (RWRRPIRRRPIRPPFWR-CONH2) and a consensus sequence from proline-rich antimicrobial peptides, called consP1 (VRKPPYLPRPRPRPL-CONH2).…”

The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

“…than the amount of Trp residues occurring in the sequence (Chan et al, 2006;Shang et al, 2020). Therefore, the Trp residue was selected as the basic components for de novo design of AMPs in this study because of its superiority to bioactivity of peptide.…”

“…This insertion of Trp-rich peptides was mainly dependent on the hydrogen bonds formed by aromatic side chain and the bilayer surface, which were equipped with a dipole moment of about 2.1D. Meanwhile, bacterial insertion activity of Trp-rich peptides mainly relied on the position of Trp residues rather than the amount of Trp residues occurring in the sequence ( Chan et al, 2006 ; Shang et al, 2020 ). Therefore, the Trp residue was selected as the basic components for de novo design of AMPs in this study because of its superiority to bioactivity of peptide.…”

In Silico MLST, SCCmec and SPA Typing OF Human MRSA Strains and Determination of Antimicrobial Resistance Genes

“…Methicillin-resistant Staphylococcus aureus (MRSA) is an important health problem worldwide due to its multi-drug resistance ability (1). MRSA has been one of the leading pathogens since it was identified in 1960 and is recognized as one of the primary pathogens of nosocomial and community-associated infections globally (2,3). Staphylococcus aureus strains carrying the mecA gene are defined as MRSA.…”