Gliotoxin is Antibacterial to Drug-resistant Piscine Pathogens

Haoran Feng,Sen Liu,SUMINGZHI,김은라,홍종기,정지형 한국생약학회 2018 Natural Product Sciences Vol.24 No.4

By activity-guided fractionation, gliotoxin was isolated as an antibacterial metabolite of the fungus Penicillium decumbens which was derived from the jellyfish Nemopilema nomurai. Gliotoxin was further evaluated for antibacterial activity against several piscine and human MDR (multidrug resistance) pathogens. Gliotoxin showed significant antibacterial activity against Gram-positive piscine pathogens such as Streptococcus iniae FP5228, Streptococcus iniae FP3187, Streptococcus parauberis FP3287, Streptococcus parauberis SPOF3K, S. parauberis KSP28, and Lactococcus garvieae FP5245. Gliotoxin showed strong activity especially against S. parauberis SPOF3K and S. iniae FP5228, which are resistant to oxytetracycline. It is noteworthy that gliotoxin effectively suppressed streptococci which are the major pathogens for piscine infection and mortality in aquaculture industry. Gliotoxin also showed strong antibacterial activity against multidrug- resistant human pathogens (MDR) including Enterococcus faecium 5270 and MRSA (methicillin-resistant Staphylococcus aureus) 3089.

Bactericidal Effect of Cecropin A Fused Endolysin on Drug-Resistant Gram-Negative Pathogens

Lim, Jeonghyun,Hong, Juyeon,Jung, Yongwon,Ha, Jaewon,Kim, Hwan,Myung, Heejoon,Song, Miryoung The Korean Society for Microbiology and Biotechnol 2022 Journal of microbiology and biotechnology Vol.32 No.6

The rapid spread of superbugs leads to the escalation of infectious diseases, which threatens public health. Endolysins derived from bacteriophages are spotlighted as promising alternative antibiotics against multi-drug resistant bacteria. In this study, we isolated and characterized the novel Salmonella typhimurium phage PBST08. Bioinformatics analysis of the PBST08 genome revealed putative endolysin ST01 with a lysozyme-like domain. Since the lytic activity of the purified ST01 was minor, probably owing to the outer membrane, which blocks accessibility to peptidoglycan, antimicrobial peptide cecropin A (CecA) was fused to the N-terminus of ST01 to disrupt the outer membrane. The resulting CecA::ST01 has been shown to have increased bactericidal activity against gram-negative pathogens including Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Enterobacter cloacae and the most affected target was A. baumannii. In the presence of 0.25 µM CecA::ST01, A. baumannii ATCC 17978 strain was completely killed and CCARM 12026 strain was wiped out by 0.5 µM CecA::ST01, which is a clinical isolate of A. baumannii and resistant to multiple drugs including carbapenem. Moreover, the larvae of Galleria mellonella could be rescued up to 58% or 49% by the administration of CecA::ST01 upon infection by A. baumannii 17978 or CCARM 12026 strain. Finally, the antibacterial activity of CecA::ST01 was verified using 31 strains of five gram-negative pathogens by evaluation of minimal inhibitory concentration. Thus, the results indicate that a fusion of antimicrobial peptide to endolysin can enhance antibacterial activity and the spectrum of endolysin where multi-drug resistant gram-negative pathogens can be efficiently controlled.

Clinical manifestations of pneumonia according to the causative organism in patients in the intensive care unit

( Jung Kyu Lee ),( Jinwoo Lee ),( Young Sik Park ),( Chang Hoon Lee ),( Jae Joon Yim ),( Chul Gyu Yoo ),( Young Whan Kim ),( Sung Koo Han ),( And Sang Min Lee ) 대한내과학회 2015 The Korean Journal of Internal Medicine Vol.30 No.6

Background/Aims: Whether the causative organism influences the clinical course of pneumonia in the intensive care unit (ICU) is controversial. We assessed the clinical manifestations and prognosis of pneumonia according to the causative pathogens in patients in a medical ICU. Methods: A retrospective observational study was performed in a medical ICU. Among 242 patients who were admitted to the ICU, 103 who were treated for pneumonia were analyzed. Results: The causative pathogen was identified in 50 patients (49.0%); 22 patients (21.6%) had multidrug-resistant (MDR) pathogens. The distribution of causative micro-organisms was Staphylococcus aureus (20%), Pseudomonas species (16%), Klebsiella pneumoniae (14%), and Acinetobacter baumannii (12%). No significant difference in ICU mortality rate, duration of ICU stay, duration of mechanical ventilation, or frequencies of re-intubation and tracheostomy were detected based on the identification of any pathogen. In sub-analyses according to the pneumonia classification, the number of pathogens identified did not differ between pneumonia types, and a higher incidence of identified MDR pathogens was detected in the hospital-acquired pneumonia group than in the community-acquired or healthcare- acquired pneumonia groups. However, the clinical outcomes of pneumonia according to identification status and type of pathogen did not differ significantly between the groups. Conclusions: Neither the causative micro-organism nor the existence of MDR pathogens in critically ill patients with pneumonia was associated with the clinical outcome of pneumonia, including ICU mortality. This result was consistent regardless of the pneumonia classification.

Evaluation of the hepato‑renal functions and antimicrobial activity of fatty amido benzoic acid synthesised from Citrullus colocynthis seed oil

Adewuyi Adewale,Otuechere Chiagoziem A.,Ellah Nkechi H.,Kaki Shiva Shanker,Fayemi Scott O.,Adeosun Charles B. 한국응용생명화학회 2021 Applied Biological Chemistry (Appl Biol Chem) Vol.64 No.1

Rapid progression in resistance to antimicrobial agents by pathogenic organisms is a serious concern. This study aimed to synthesize fatty amido benzoic acid (FBA) from Citrullus colocynthis seed oil (CCO) and evaluate its safety profile as an alternative bioactive agent for combating drug-resistant pathogens. FBA was synthesised through simple chemical reaction route and examined for its antioxidant activity and antimicrobial capacity against selected drugresistant microorganisms. Effect of FBA on hepato-renal function makers and oxidative stress was also examined using Wistar rats. Density functional theory (DFT) approach was employed to understand the action of FBA with the aid of lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO). Gas Chromatography (GC) revealed the most abundant fatty acid in CCO to be C18:2 (55.88%). Results from Fourier transformed infrared spectroscopy (FTIR), and proton nuclear magnetic resonance (1HNMR) confirmed the synthesis of FBA with a yield of 97.10%. FBA exhibited antioxidant potential ( IC50 of 1.96 μg mL−1) as well as antimicrobial potency. Minimum inhibitory concentration (MIC) of FBA was 0.026 mg mL−1. Biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, hydrogen peroxide, and lipid peroxidation were significantly elevated in rats administered high dose FBA (100 mg kg−1). Histology of the liver and kidney confirmed the biochemical results. Furthermore, mechanism of action of FBA could be described by quantum chemical analysis to be via nucleophilic interaction, which may be viewed electronically as donor–acceptor interaction. The study presents FBA as a promising antimicrobial agent for combating drug-resistant pathogenic organisms.

Amycolatopsis sp. KCTC 29142로부터 유래된 siderochelin A의 다제 내성 균주에 대한 항균활성

이동령,성금화,이성권,홍희전,송재경,양승환,서주원,Lee, Dong-Ryung,Cheng, Jinhua,Lee, Sung-Kwon,Hong, Hee-Jeon,Song, Jaekyeong,Yang, Seung Hwan,Suh, Joo-Won The Microbiological Society of Korea 2016 미생물학회지 Vol.52 No.3

본 연구에서는 신규 Amycolatopsis 균주 KCTC 29142를 분리하여 형태학적 관찰, 계통분석 및 화학분류학적 분석 등 다상 분류분석을 통해 분석하였다. KCTC 29142 균주의 에틸아세테이트추출물은 강한 항균활성을 나타났고, 활성물질은 철 이온 킬레이트 물질인 siderochelin A로 동정되었다. 본 연구에서 분리된 siderochelin A는 다제내성균인 Acinetobacter baumanii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA), 및 Escherichia coli (E. coli)에 대해 강한 활성을 보였고, 임상에서 분리된 다제내성균에 대한 MIC를 결정하였다. A novel Amycolatopsis strain KCTC 29142 was isolated and characterized based on the polyphasic taxonomic analysis including morphological observation, phylogenetic analysis, physiological and chemotaxonomic characteristics. The ethyl acetate extract of strain KCTC 29142 culture broth showed strong antibacterial activity and the active compound was identified as siderochelin A, a ferrous-ion chelating compound. In this study, siderochelin A showed good activity against multi-drug resistant pathogens, including Acinetobacter baumanii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA), and Escherichia coli (E. coli). The minimum inhibitory activity against clinical isolates was also determined.

35종 해조류 추출물의 병원성 세균 및 Candida sp. 진균에 대한 항균 활성 평가

김미선 ( Mi Sun Kim ),권경진 ( Kyung Jin Kwon ),이민진 ( Min Jin Lee ),안선미 ( Seon Mi Ahn ),손호용 ( Ho Yong Sohn ) 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 2012 한국미생물·생명공학회지 Vol.40 No.2

In the course of this study aimed at the development of functional food ingredients from seaweeds, the in vitro antimicrobial activities of methanol extracts prepared from 35 different seaweeds (17 phaeophyta, 11 rhodophyta and 7 chlorophyta) were determined against food-borne diseases and pathogenic microorganisms including multi-drug resistant (MDR) Pseudomonas sp. and Candida sp. Based on disc-diffusion assays at 500 g/disc concentration of the methanol extracts, Ishige okamurai, I. foliacea, Sargassum confusum, and S. yamade exhibited strong antibacterial activities in a broad-spectrum, except against Pseudomonas aeruginosa. In addition to the latter four seaweeds, Ecklonia stolonifera, E. cava and Eisenia bicyclis also demonstrated antifungal activity against C. albicans. Among these 8 selected seaweeds, I. okamurai, I. foliacea, and S. yamade exhibited strong hemolytic activity (55-93%) at 500 g/ml against human RBC. Organic solvent sequential fractions using hexane, ethylacetate and butanol, and water residues were prepared from the 8 selected seaweeds and their anti-Candida sp. activities were further determined. The ethylacetate and butanol fraction of I. okamurai, and the hexane fraction of I. foliacea demonstrated antifungal activity against MDR-pathogenic Candida sp. Although the solvent fractions had no activity against MDR-Pseudomonas sp., our results suggest that seaweeds, especially Ishige okamurai, I. foliacea, S. confusum, and S. yamade could be developed as broad-spectrum antimicrobial ingredients.

넙치 (Paralichthys olivaceus) 병어에서 분리된 연쇄상구균의 다양성

김종훈 ( Kim Jong Hun ),김은희 ( Kim Eun Hui ) 한국수산과학회 2003 한국수산과학회지 Vol.36 No.6

N/A To evaluate the biological diversity of fish pathogenic streptococci, 35 strains isolated from diseased olive flounder (Paralichthys olivaceus), were analyzed using a random amplified polymorphic DNA (RAPD) technique with the oligonucleotide commercial primer 6 (Amersham Biosciences). Api 20 Strep test, drug resistance, and artificial infection were carried out for hrther characterization of the isolates. RAPD fingerprints showed similar pattern in 25 strains (about 71.4% of 35 isolates) and these strains were designed as RA group I. Similarities greater than 44% were obtained when the Dice coefficient was applied among the isolates of RA I. On the other hand, the reference Streptococcus iniue showed a similar RAPD profile to the isolates with similarity levels of 40-93.3%. RA I was suggested to be the dominant group isolated from olive flounder suffering from streptococcosis. However, the isolates of RA1 group were not classified into the same species by the Api 20 Strep identification system. There was no peculiarity in drug resistance patterns of RA I group isolates against 7 antibacterial agents. However, only 3 of 25 isolates (0.12%) showed oxytetracycline (OTC) resistance and OTC might be a useful chemotherapeutic agent in controlling the streptococcosis by strains of RA I group in olive flounder. Fish injected intraperitoneally with 10 CFU of an isolate of RA I and RA Ⅲ group showed 60% and 50% accumulative mortality for 20 days, respectively (20% in control or RA 11). However futher comparative studies about differences in virulence between isolates are needed.