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Zehava Eichenbaum

Associate Professor    Associate Director of Graduate Program

Ph.D. in Molecular Genetics, Weizmann Institute, 1992


Bacterial Genetics and Pathogenesis
Molecular Genetics and Biochemistry


Bacterial Genetics and Pathogenesis

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.