Eichenbaum, Zehava - Georgia State University

个人简介

Ph.D. Molecular Genetics Weizmann Institute 1992 Bacterial Genetics and Pathogenesis Molecular Genetics and Biochemistry

研究领域

The research interests of this laboratory are in the area of bacterial pathogenesis. We study the molecular genetics of iron regulation and iron-uptake mechanisms in the pathogenic streptococci: S. pyogenes (group A streptococcus) and S. agalactiae (group B streptococcus). S. pyogenes is an obligate human pathogen capable of producing a variety of supportive skin and throat infections. These infections can trigger serious post infection complications such as rheumatic fever, acute glomerulonephritis, and rheumatic heart disease. S. pyogenes also causes several severe invasive infections such as myositis, narcotizing fasciitis and streptococcal toxic shock syndrome. Since the late 1980’s an increase in the frequency and the severity of the serious streptococcal infections has been observed worldwide. S. agalactiae can lead to dangerous diseases such as bacteremia, pneumonia, and meningitis. It emerged as a major pathologic threat to infants in the 1960’s and continued to be the leading cause of maternal and neonatal morbidity in 1990’s. Elderly and young adults with diabetes, cancer, or HIV infection are also at increased risk. Iron limitation has been demonstrated to be of critical importance for virulence of many pathogenic bacteria. In human tissues, the concentration of iron available to the infecting bacteria is very low. Therefore, the ability of a pathogen to obtain iron from its host is a fundamental requirement for establishment of infection. We have initiated studies to determine the role of iron limitation on both S. pyogenes and S. agalactiae, as it has not been previously investigated in these pathogenic streptococci. Since the study of Streptococcus species has been restricted due to the lack of an efficient genetic system we have also developed and characterized the use of several genetic tools including transposon delivery vectors (based on Tn917), reporter genes, and systems to regulate gene expression. We have established conditions for iron starvation of S. pyogenes in liquid culture, and have begun to study the effect of iron starvation on the expression and secretion of S. pyogenes products. We found that the streptococcal plasmin receptor (Plr, also known as SDH for Streptococcal surface glyceraldhyde dehydrogenase) is released from the cell surface when the bacteria are starved for iron. Plr is a protein with multiple activity including ADP ribosylation. This finding suggests that Plr may function as a soluble virulence factor during infection. We have developed an agar plate assay and used it to identify iron binding proteins of human origin S. pyogenes can obtain iron. Surprisingly for a mucosal pathogen, the extracellular host proteins transferrin and lactoferrin could not be utilized. Currently, our laboratory is engaged in identifying and characterizing streptococcal genes involved in iron utilization from hemin and hemoglobin.

近期论文

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Induction of the pho regulon and polyphosphate synthesis against spermine stress in Pseudomonas aeruginosa. Peng YC, Lu C, Li G, Eichenbaum Z, Lu CD. Mol Microbiol. 2017 Jun;104(6):1037-1051. doi: 10.1111/mmi.13678. Epub 2017 Apr 12. In vitro heme biotransformation by the HupZ enzyme from Group A streptococcus. Sachla AJ, Ouattara M, Romero E, Agniswamy J, Weber IT, Gadda G, Eichenbaum Z. Biometals. 2016 Aug;29(4):593-609. doi: 10.1007/s10534-016-9937-1. Epub 2016 May 6. The GAS PefCD exporter is a MDR system that confers resistance to heme and structurally diverse compounds. Sachla AJ, Eichenbaum Z. BMC Microbiol. 2016 Apr 19;16:68. doi: 10.1186/s12866-016-0687-6. Heme-bound SiaA from Streptococcus pyogenes: Effects of mutations and oxidation state on protein stability. Akbas N, Draganova EB, Block DR, Sook BR, Chan YF, Zhuo J, Eichenbaum Z, Rodgers KR, Dixon DW. J Inorg Biochem. 2016 May;158:99-109. doi: 10.1016/j.jinorgbio.2015.10.016. Epub 2015 Nov 14. The crimson conundrum: heme toxicity and tolerance in GAS. Sachla AJ, Le Breton Y, Akhter F, McIver KS, Eichenbaum Z. Front Cell Infect Microbiol. 2014 Nov 5;4:159. doi: 10.3389/fcimb.2014.00159. eCollection 2014. The phosphoenolpyruvate phosphotransferase system in group A Streptococcus acts to reduce streptolysin S activity and lesion severity during soft tissue infection. Gera K, Le T, Jamin R, Eichenbaum Z, McIver KS. Infect Immun. 2014 Mar;82(3):1192-204. doi: 10.1128/IAI.01271-13. Epub 2013 Dec 30. Kinetics of heme transfer by the Shr NEAT domains of Group A Streptococcus. Ouattara M, Pennati A, Devlin DJ, Huang YS, Gadda G, Eichenbaum Z. Arch Biochem Biophys. 2013 Oct 15;538(2):71-9. doi: 10.1016/j.abb.2013.08.009. Epub 2013 Aug 28. The streptococcal hemoprotein receptor: a moonlighting protein or a virulence factor? Eichenbaum Z. Virulence. 2012 Nov 15;3(7):553-5. doi: 10.4161/viru.22440. Epub 2012 Nov 15.