Jang Won Yoon
Kangwon National University, South Korea
Title: Role of stringent control in the pathogenesis of enteropathogenic Escherichia coli and its macrophage response
Biography
Jang W. Yoon has his expertise in molecular pathogenesis of zoonotic bacterial pathogens. His research interest is understanding the molecular mechanisms of enterohemorrhagic and enteropathogenic E. coli infections and their host interactions during infection. He was found for the first time that the 93-kb virulence plasmid in almost all the clinical isolates of enterohemorrhagic E. coli O157:H7 encodes a second myristoyl transfrerase which are thermoregulated by intrinsically curved DNA (Yoon et al, 2004). His laboratory is now working on bacterial signaling molecules and questions how they involve bacterial pathogenesis and host responses.
Abstract
Like quorum sensing, stringent control is a global gene regulatory system present in bacteria. Under starved and stressful environments, a stringent response regulator ppGpp is rapidly synthesized and alters many cellular processes such as growth, metabolic activity, and virulence. To define the role of stringent control in enteropathogenic Escherichia coli (EPEC), a major cause of infantile diarrhea, a ppGpp0 mutant of the EPEC E2348/69 strain was created and examined its virulence attenuation. Our experimental analyses demonstrated that the lack of ppGpp in the EPEC E2348/69 strain (i) repressed Gad expression and survival rate (ii) derepressed the expression of Type IV bundle forming pili (BFP), (iii) repressed the locus of enterocyte and effacement (LEE) pathogenicity island encoding a functional Type III secretion system (TTSS), (iv) could not induce the EPEC-mediated killing of Caenorhabditis elegans, and (v) altered the outer membrane structure and integrity. The whole genome-scale omics analyses revealed the 854 EPEC genes that were differentially expressed by ppGpp (cut-offs of > 2 folds), including the LEE, bfp, per, and gad operons. Moreover, the ppGpp0 mutant altered the macrophage response when infected, compared to the wildtype strain. Taken together, our results imply that ppGpp signaling plays an important role in both virulence and macrophage response in EPEC.
Hsin-Yeh Lin
Chang Gung Memorial Hospital, Taiwan
Title: Significant Intestinal Microbiota Differences in Biliary Atresia Infants with Distinct Clinical Outcome
Biography
Hsin-Yeh, Lin has completed general pediatrics training, and is furthering her medical training in Chang Gung Memorial Hospital. She is now in her first year of Pediatric Gastroenterology & hepatology fellowship, and is still in the initial stage of pursuing knowledge in both clinical and endoscopic skills.
Abstract
Intestinal microbiota has been thought to be associated with human health and disease. Its impact on hepatobiliary disease in infancy such as extra-hepatic biliary atresia, is of limited study. Our study aimed to figure out the association between changes in intestinal microbiota and the disease outcome of infant with biliary atresia. Two infants with biliary atresia received Kasai’s operation before 60 days of age. The infant with good outcome had jaundice resolved gradually within one month and the other infant with poor outcome had progressive liver cirrhosis and finally underwent liver transplantation when 6-month-old. Their fecal samples were collected at two time points with the interval of 1 month. Universal primers for the 16S variable regions V1–3 and V3–5 were used for polymerase chain reaction (PCR) amplification. Sequences were aligned and microbiota composition was characterized compared to the Human Microbiome Project (HMP) database. All statistical tests were performed using SAS software v. 8 for Windows. A significantly lower Shannon diversity index (entropy score) of the intestinal microbiota in patient with poor outcome was found compared to the one with good outcome. Patient with poor outcome has greater richness in phylum level of Bacteroidetes, while patient with good outcome has higher Proteobacteria. Other than decreasing in microbial diversity, there was an overall significant higher richness in Bacteroides (P< 0.01) in patient with poor outcome and Escherichia in patient with good outcome (P= 0.03). A significantly increased species composition of Bifidobacterium breve (P= 0.0159) was found in the later phase of good-outcome patient compared to its early phase. In conclusion, the microbiota community was significantly different in biliary atresia infants with distinct outcome through correlated bile acid dysbiosis. The results will facilitate further studies of the interaction between the intestinal microbiota and hepatobiliary disease in children and infants.
