Dataset Information

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 ?g/mouse) or TP4 (50 ?g/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.

SUBMITTER: Pan CY

PROVIDER: S-EPMC4413212 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Piscidin is highly active against carbapenem-resistant Acinetobacter baumannii and NDM-1-producing Klebsiella pneumonia in a systemic Septicaemia infection mouse model.

Pan Chieh-Yu CY Chen Jian-Chyi JC Chen Te-Li TL Wu Jen-Leih JL Hui Cho-Fat CF Chen Jyh-Yih JY

Marine drugs 20150414 4

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 surviva ...[more]

PMID: 25874924

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Project description:Carbapenem-resistant Acinetobacter baumannii (CRAB), which belonged to global clones 1 (GC1) or 2 (GC2), has been widely reported and become a global threat. However, non-GC1 and non-GC2 CRAB strains are not well-studied, especially for those with rare phenotype. Here, one pyomelanin-producing CRAB strain (A. baumannii DETAB-R21) was isolated from oral swab in the ICU. Antimicrobial susceptibility testing showed it was resistant to carbapenems, ceftazidime, levofloxacin, and ciprofloxacin. DETAB-R21 was ST164Pas and ST1418Oxf with KL47 and OCL5, respectively. Whole-genome sequencing (WGS) analysis revealed chromosome contained three copies of blaOXA-23 on three 4,805-bp Tn2006 composite transposons with various novel 9-bp target site duplications (TSD). A Tn125-like structure, including blaNDM-1, a novel 4,343 bp composite transposon encoding blaCARB-16, and three prophage regions were also identified. Importantly, hmgA was interrupted by a Tn2006 and contributed to pyomelanin production and further confirmed by hmgA overexpression. Furthermore, A. baumannii irradiated with UV light, DETAB-R21 showed a higher relatively survival rate compared to a control strain that did not produce pyomelanin. No effects of pyomelanin were observed on disinfectants susceptibility, growth, or virulence. In conclusion, pyomelanin-producing CRAB carrying the blaNDM-1 and blaOXA-23 genes embedded in the bacterial chromosome is of grave concern for health care settings, highlighting the need for effective measures to prevent further dissemination. IMPORTANCE Pyomelanin production is a quite rare phenotype in A. baumannii. Moreover, the mechanisms leading to the pyomelanin production was still unclear. Here, we for the first time, confirmed the mechanism of pyomelanin production, and further investigated the impact of pyomelanin on disinfectants susceptibility, growth, virulence, and UV irradiation. More importantly, many mobile genetic elements (MGEs), including three copies of Tn2006 composite transposons, one copy of blaNDM-1 on the Tn125-like structure and three prophage regions, were identified in the chromosome, demonstrated strong plasticity of A. baumannii genome. Our study provides important insights into the new rare ST164Pas A. baumannii strain with high level carbapenem resistance, which is of great threat for patients. These findings will provide important insights into the resistance gene transfer via transposition events and further spread in the clinic.

Project description:Carbapenem-resistant determinants and their surrounding genetic structure were studied in Acinetobacter spp. from neonatal sepsis cases collected over 7 years at a tertiary care hospital. Acinetobacter spp. (n = 68) were identified by ARDRA followed by susceptibility tests. Oxacillinases, metallo-?-lactamases (MBLs), extended-spectrum ?-lactamases and AmpCs, were detected phenotypically and/or by PCR followed by DNA sequencing. Transconjugants possessing the bla NDM-1(New Delhi metallo-?-lactamase) underwent further analysis for plasmids, integrons and associated genes. Genetic environment of the carbapenemases were studied by PCR mapping and DNA sequencing. Multivariate logistic regression was used to identify risk factors for sepsis caused by NDM-1-harboring organisms. A. baumannii (72%) was the predominant species followed by A. calcoaceticus (10%), A. lwoffii (6%), A. nosocomialis (3%), A. junni (3%), A. variabilis (3%), A. haemolyticus (2%), and 14TU (2%). Fifty six percent of the isolates were meropenem-resistant. Oxacillinases present were OXA-23-like, OXA-58-like and OXA-51-like, predominately in A. baumannii. NDM-1 was the dominant MBL (22%) across different Acinetobacter spp. Isolates harboring NDM-1 also possessed bla (VIM-2, PER-1, VEB-2, CTX-M-15), armA, aac(6')Ib, aac(6')Ib-cr genes. bla NDM-1was organized in a composite transposon between two copies of ISAba125 in the isolates irrespective of the species. Further, OXA-23-like gene and OXA-58-like genes were linked with ISAba1 and ISAba3 respectively. Isolates were clonally diverse. Integrons were variable in sequence but not associated with carbapenem resistance. Most commonly found genes in the 5' and 3'conserved segment were aminoglycoside resistance genes (aadB, aadA2, aac4'), non-enzymatic chloramphenicol resistance gene (cmlA1g) and ADP-ribosylation genes (arr2, arr3). Outborn neonates had a significantly higher incidence of sepsis due to NDM-1 harboring isolates than their inborn counterparts. This study demonstrates the significance of both A. baumannii and other species of Acinetobacter in cases of neonatal sepsis over an extended period. Oxacillinases and bla NDM-1 are the major contributors to carbapenem resistance. The dissemination of the bla NDM-1 is likely linked to Tn125 in diverse clones of the isolates.

Dataset Information

Piscidin is highly active against carbapenem-resistant Acinetobacter baumannii and NDM-1-producing Klebsiella pneumonia in a systemic Septicaemia infection mouse model.

Publications

Piscidin is highly active against carbapenem-resistant Acinetobacter baumannii and NDM-1-producing Klebsiella pneumonia in a systemic Septicaemia infection mouse model.

Similar Datasets

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