Overcoming Planktonic and Intracellular Staphylococcus aureus-Associated Infection with a Cell-Penetrating Peptide-Conjugated Antimicrobial Peptide.

Abstract

Staphylococcus aureus is a primary pathogen responsible for causing postoperative infections as it survives and persists in host cells, including osteoblasts and macrophages. These cells then serve as reservoirs resulting in chronic infections. Most traditional antibiotics have poor effects on intracellular S. aureus because they cannot enter the cell. Herein, a cell-penetrating peptide TAT-KR-12 was derived from the trans-activating transcription (TAT) peptide and KR-12 (residues 18-29 of human cathelicidin LL-37). The TAT acts as a "trojan horse" to deliver KR-12 peptide into the cells to kill S. aureus. Moreover, effective antibacterial properties and biocompatibility were observed in vitro, demonstrating that TAT-KR-12 is effective not only in eliminating planktonic S. aureus, but also in eliminating intracellular S. aureus cells in vitro. TAT-KR-12, as with LL-37, also elicits strong anti-inflammatory activities in LPS-stimulated macrophages, as demonstrated by significant inhibition of NO, TNF-α, and IL-1β expression and secretion from LPS-stimulated RAW264.7 cells. In the subcutaneous infection mouse model of planktonic and intracellular infections, the growth of S. aureusin vivo is evidently inhibited without cytotoxicity. These results suggest that the novel antimicrobial TAT-KR-12 may prove to be an effective treatment option to overcome antibiotic resistance caused by intracellular bacterial infections.

• Authors: Shicheng Huo, Chi Chen, Zhuocheng Lyu, Shutao Zhang, You Wang, Bin'en Nie, Bing Yue
• Journal: ACS infectious diseases (ACS Infect Dis) Vol. 6 Issue 12 Pg. 3147-3162 (12 11 2020) ISSN: 2373-8227 [Electronic] United States
• PMID: 33236626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell-Penetrating Peptides
• Pore Forming Cytotoxic Proteins

Topics

• Cell-Penetrating Peptides
• Plankton
• Pore Forming Cytotoxic Proteins
• Staphylococcal Infections (drug therapy)
• Staphylococcus aureus (pathogenicity)