A novel chemosynthetic peptide with ß-sheet motif efficiently kills Klebsiella pneumoniae in a mouse model

Abstract

Klebsiella pneumoniae ( Kp ) is one of the most common pathogens in nosocomial infections and is increasingly becoming multiple drug resistant. However, the molecular pathogenesis of Kp in causing tissue injury and dysregulated host defense remains elusive, further dampening the development of novel therapeutic measures. We have previously screened a series of synthetic antimicrobial beta-sheet forming peptides and identified a peptide (IRIKIRIK; ie, IK8L) with a broad range of bactericidal activity and low cytotoxicity in vitro. Here, employing an animal model, we investigated the antibacterial effects of IK8L in acute infection and demonstrated that peritoneal injection of IK8L to mice down-regulated inflammatory cytokines, alleviated lung injury, and importantly, decreased mortality compared to sham-injected controls. In addition, a math model was used to evaluate in vivo imaging data and predict infection progression in infected live animals. Mechanistically, IK8L can kill Kp by inhibiting biofilm formation and modulating production of inflammatory cytokines through the STAT3/JAK signaling both in vitro and in vivo. Collectively, these findings reveal that IK8L may have potential for preventing or treating Kp infection.

Annexin A2 Regulates Autophagy in Pseudomonas aeruginosa Infection through the Akt1–mTOR–ULK1/2 Signaling Pathway

“…Exons 3 and 4 of anxa2 were disrupted with a cassette containing neomycin phosphotransferase driven by the phosphoglucokinase promoter to generate anxa2 2/2 mice (22). Animals were kept in a specific pathogenfree facility at the University of North Dakota (23). All animal studies were approved by the University of North Dakota Institutional Animal Care and Use Committee and performed in accordance with the animal care and institutional guidelines (IACUC approval #1204-4).…”

“…Membranes were incubated with the primary Abs overnight. Labeling of the first Abs was detected using relevant secondary Abs conjugated to HRP and detected using ECL reagents (23).…”

Type I CRISPR-Cas targets endogenous genes and regulates virulence to evade mammalian host immunity

“…Cells were treated as above, and incubated in 0.5 mg/ml MTT (Sigma-Aldrich ) for 4 h. Reaction was stopped by stop solution and left at room temperature overnight for complete dissolution of formazan and absorbance at 560 nm was recorded using a multiscan plate reader to quantify the concentration of superoxide anion [46].…”

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“…Polymer nanoparticles, micelles, nanosponges ( 37 , 38 ), nanogels ( 39 ), and nanofibers for wound healing have been widely investigated ( 40 , 41 ). Natural polymers that are extensively used in nanoparticle synthesis include chitosan, dextran, albumin, heparin, gelatin, and collagen ( 42 , 43 ).…”