University of Wisconsin USA
Title: Post-transcriptional modification of RNA: Effect on biology and virulence of Salmonella
Amin A Fadl obtained his PhD from University of Connecticut, USA and completed a postdoctoral training at the University of Texas Medical Branch. Currently, he is an Assistant Professor of Microbiology at the University of Wisconsin-Madison. His research focuses on the molecular pathogenesis, immune and inflammatory responses, and host-pathogen interaction of Salmonella. He has published more than 46 papers in reputed journals.
GidA together with another protein known as MnmE catalyze the tRNA modification required for correct gene translation. Our study have shown that GidA and MnmE complex together to modulate virulence genes in Salmonella as indicated by in vitro experiments, animal model and a global transcriptome and proteome analyses. Mice immunized with the gidA, mnmE and gidA/mnmE mutants were protected against a lethal dose of wild-type. The mechanistic basis of such protection was identified to be humoral and cellular immunity with the humoral immune response potentially being the main mechanism of protection. The gidAB operon includes the gidA and gidB genes. The gidB encodes a methyltransferase enzyme responsible for methylation of 16S ribosomal RNA in Escherichia coli. Deletion of Salmonella gidB gene indicated a compromised overall bacterial fitness, significantly reduced motility and showed a filamentous morphology under the stress of nalidixic acid. Most importantly, deletion of gidB conferred high-level resistance to the aminoglycoside antibiotics. Additionally, transcriptional repressor AsnC, located upstream of the gidAB operon, is thought to negatively regulate the gidAB operon post-transcriptionally. Therefore, we investigated the role of AsnC and the environmental factors affecting gene expression in the gidAB operon using transcriptional and proteomic analyses. Taken together, these data indicated that GidA, GidB and MnmE enzymes play a significant role in modulation of biological and virulence characteristics in Salmonella under stress conditions. Further, these studies indicated that the gidAB operon is regulated at post-transcriptional level by glucose and stressful conditions as well as the AsnC protein.
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