Piscidin is Highly Active against Carbapenem-Resistant Acinetobacter baumannii and NDM-1-Producing Klebsiella pneumonia in a Systemic Septicaemia Infection Mouse Model

Abstract

This study was designed to investigate the antimicrobial activity of two synthetic antimicrobial peptides from an aquatic organism, tilapia piscidin 3 (TP3) and tilapia piscidin 4 (TP4), in vitro and in a murine sepsis model, as compared with ampicillin, tigecycline, and imipenem. Mice were infected with (NDM-1)-producing K. pneumonia and multi-drug resistant Acinetobacter baumannii, and subsequently treated with TP3, TP4, or antibiotics for different periods of time (up to 168 h). Mouse survival and bacterial colony forming units (CFU) in various organs were measured after each treatment. Toxicity was determined based on observation of behavior and measurement of biochemical parameters. TP3 and TP4 exhibited strong activity against K. pneumonia and A. baumannii in vitro. Administration of TP3 (150 μg/mouse) or TP4 (50 μg/mouse) 30 min after infection with K. pneumonia or A. baumannii significantly increased survival in mice. TP4 was more effective than tigecycline at reducing CFU counts in several organs. TP3 and TP4 were shown to be non-toxic, and did not affect mouse behavior. TP3 and TP4 are able at potentiate anti-Acinetobacter baumannii or anti-Klebsiella pneumonia drug activity, reduce bacterial load, and prevent drug resistance, indicating their potential for use in combating multidrug-resistant bacteria.

The rapid spread of carbapenem-resistant Enterobacteriaceae

“…Cationic antimicrobial peptides (AMPs) are an ancient feature of multicellular immune systems that hold potential for novel bacterial infection treatments. Two piscidin family AMPs isolated from tilapia ( Oreochromis niloticus ) in Taiwan in 2012 exhibited in vivo bacteriostatic effects yielding superior survival outcomes compared to tigecycline and imipenem in a mouse sepsis model infected with bla NDM-1 producing K. pneumoniae [Pan 2015]. …”

Study of the Antimicrobial Activity of Tilapia Piscidin 3 (TP3) and TP4 and Their Effects on Immune Functions in Hybrid Tilapia (Oreochromis spp.)

“…Five different tilapia piscidin cDNA clones have been isolated and named tilapia piscidin 1 (TP1), TP2, TP3, TP4, and TP5 [1]. TP3 exerts significant activity against bacteria [2,3], and TP4 exhibits cell proliferation-stimulating, wound closure-inducing, and bacterial infection-reducing activity [4–6]. The antimicrobial peptide piscidin-1 has been reported to have anti-nociceptive effects [1,7].…”

“…Several recent articles have reviewed a variety of alternatives to the use of antibiotics, and one promising treatment is the use of antimicrobial peptides (AMPs) [13]. The medical industry is increasingly recognizing the potential benefits of using AMPs instead of antibiotics to control bacterial infections such as acne and catheter-related infections [13,14], and fish AMPs, such as TP3 and TP4, act as anti-infective agents with high potency against human pathogens [2,5,6]. However, no previous studies have adequately examined the antimicrobial activity of TP3 or TP4 against V .…”

“…vulnificus infections include doxycycline, cephalosporin, fluoroquinolone, and trimethoprim-sulfamethoxazole plus aminoglycosides, but due to the emergence of these newly resistant bacteria, there is an urgent need to develop alternative biocontrol agents, such as AMPs. Recently, we demonstrated a high level of activity in a piscidin against carbapenem-resistant Acinetobacter baumannii and NDM-1-producing Klebsiella pneumonia in a mouse model of systemic septicemia [6]. In addition, TP3 and TP4 exhibited potent and broad-spectrum antimicrobial properties against these bacteria, which suggests that either may be a strong candidate for development as an antimicrobial agent for use in aquaculture.…”

Establishment of Experimental Murine Peritonitis Model with Hog Gastric Mucin for Carbapenem-Resistant Gram-Negative Bacteria

“…Several animal infection models for carbapenem-resistant Gram-negative bacteria of clinical isolates have been reported [567891011], each of these models involved different methods and diverse mouse strains. BALB/c, C57BL/6, Swiss-Webster, and C3 mice have been used, and the site of bacterial administration has varied ( e.g.…”