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Joint Research Seminar (29 Jul 2015)

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Joint Research Seminar

Genomics Strategic Research Theme
Centre for Genomic Sciences

Antibiotic Resistance and the Emergence of
Immune-compromised Enterococci

By

Prof Michael Q Zhang

The University of Texas at Dallas and Tsinghua University


29 July 2015 (Wed)
3:00 – 4:00pm


Seminar Room 1A, G/F
The Hong Kong Jockey Club Building for Interdisciplinary Research

5 Sassoon Road, Pokfulam, Hong Kong

 
Abstract:

Enterococcus faecalis is a Gram-positive bacterium that natively colonizes the human gastrointestinal tract and opportunistically causes life-threatening infections. Multidrug-resistant (MDR) E. faecalis strains have emerged, reducing treatment options for these infections. MDR E. faecalis strains have large genomes containing mobile genetic elements (MGEs) that harbor genes for antibiotic resistance and virulence determinants. Bacteria commonly possess genome defense mechanisms to block MGE acquisition, and we hypothesize that these mechanisms have been compromised in MDR E. faecalis. In restriction-modification (R-M) defense, the bacterial genome is methylated at cytosine (C) or adenine (A) residues by a methyltransferase (MTase), such that nonself DNA can be distinguished from self DNA. A cognate restriction endonuclease digests improperly modified nonself DNA. Little is known about R-M in E. faecalis. Here, we use NGS (both 2nd and 3rd generation) to identify DNA modifications occurring in the oral isolate OG1RF. OG1RF has one of the smallest E. faecalis genomes sequenced to date and possesses few MGEs. Single-molecule real-time (SMRT) and bisulfite sequencing revealed that OG1RF has global 5-methylcytosine (m5C) methylation at 5'-GCWGC-3' motifs. A type II R-M system confers the m5C modification, and disruption of this system impacts OG1RF electrotransformability and conjugative transfer of an antibiotic resistance plasmid. A second DNA MTase was poorly expressed under laboratory conditions but conferred global N(4)-methylcytosine (m4C) methylation at 5'-CCGG-3' motifs when expressed in Escherichia coli. Based on our results, we conclude that R-M can act as a barrier to MGE acquisition and likely influences antibiotic resistance gene dissemination in the E. faecalis species. Prof Zhang will also talk about our ongoing work on the adaptive immune system (CRISPR-cas) in Enterococcus and its implication in MDR.

About the Speaker:

Prof Michael Q ZhangProf Zhang got his BS in Mech Eng from USTC and joined the first CUSPEA (initiated by TD Lee) group studying physics in USA in 1981. After getting Statistical Physics PhD from Rutgers University in 1987, he became a postdoc at the Courant Institute of Mathematics at NYU until he became a Genome Research fellow at CSHL in 1991. He started his Computational Genomics Lab there in 1996 and became full professor in 2002. He became 1000-Talent guest professor of Tsinghua University in 2009 and moved to UTD as the Cecil H and Ida Green Distinguished endowed chair Professor in 2010.
 

ALL ARE WELCOME


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