title: Oligomerization of RNAIII-Inhibiting Peptide Inhibits Adherence and Biofilm Formation of Methicillin-Resistant Staphylococcus aureus In Vitro and In Vivo.
abstract: Biofilm formation enhances bacterial resistance and complicates treatment. Therefore, an innovative strategy is urgently needed for the treatment of Staphylococcus aureus biofilm infectious diseases. RNAIII-inhibiting peptide (RIP), as a quorum-sensing inhibitor, inhibits S. aureus biofilm formation. However, RIP possesses poor antibiofilm activity when used alone or at a low dose in vivo. The activity and stability of RIP can be enhanced by designing its derivatives through amino acid substitution, terminal modification, or oligomerization. Among the derivatives, 16P-AC significantly decreased the biofilm formation and adherence of methicillin-resistant S. aureus (MRSA) on polystyrene material by inhibiting the expression level of four biofilm formation-related genes in vitro. Moreover, 16P-AC showed excellent protective effects by decreasing the bacterial titers in the urine, kidney, stent, and bladder, as well as by inhibiting intercellular adhesion on the implanted stent, in a rat urinary tract infection model induced by MRSA. This derivative also exhibited a relatively good stability in rat plasma. Therefore, 16P-AC is a potential drug candidate to treat biofilm-associated infections caused by MRSA. The present modification strategy is feasible to improve the metabolic stability and activity of RIP in vivo.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Ruzhou
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Han
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Di
authors.initials: D
authors.lastname: Qu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Mingkai
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Jingru
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University , Xi'an, China .
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D008297:Male; D008712:Methicillin / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D012329:RNA, Bacterial; C111711:RNAIII inhibiting peptide; C096035:RNAIII, Staphylococcus aureus; D008712:Methicillin