E. coli hemolysin

Baldwin TJ, Knutton S, Sellers L, Hernandez HA, Aitken A, Williams PH Enteroaggregative Escherichia coli strains secrete a heat-labile toxin antigenically related to E. coli hemolysin. Infect Immun 1992,60 2092-2095. 

Certain cellular processes are specifically influenced by gradients of monovalent ions across the plasma membrane. It appears that stimulation of some such processes are actually counteracted by concomitant flux. Ca -dependent processes in turn may be abrogated when pores are large enough to permit rapid egress of cytoplasmic proteins. Therefore, it is useful to differentiate between three types of pores (a) those that are selectively permissive for monovalent ions (e.g. staphylococcal alpha-toxin) (b) those that are permissive for Ca and small molecules, but not for proteins (e.g. E. coli hemolysin) and (c) large pores that allow passage of macromolecules (e.g. streptolysin O). 

Suttorp N, Fiber B, SeegerW etal. (1990) Effects of E coli hemolysin on endothelial cell function. In Infect Immun 58 3796-3801. 

Hoffman et al.52, presented evidence that a single oral dose of tilorone enhanced the primary immune response to sheep red blood cells (SRBC) in mice as measured by the Jerne Plaque technique. They also reported an increase in hemolysin titer after tilorone administration. To further evaluate the action of tilorone on humoral antibody responses, Megel ef a/.3 have studied its effect on 19S and 7S production in the primary and secondary immune responses in mice. It was found that tilorone elevated 19S antibody titer on days 3 and 4 after immunization. After 9 days of continuous drug administration, the 19 S response for both groups was diminished compared to days 3 and 4 however tilorone was found to cause a significant increase in the 7S antibody production compared to controls. Tilorone also stimulated the 19S response to E. coli endotoxin, a thymus-independent antigen, on days 3 and 4 after immunization. 

Two possibly related phenomena have been found to be dependent on the flux of monovalent ions. The hypothetical common link is represented by a newly discovered family of intracellular proteases whose activity may be influenced by concentrations. Interleukin converting enzyme (ICE) is the best studied member of this family. Efflux of from monocytes leads to activation of ICE, so that the cells rapidly process and export IL-16 (Walev etal., 1995). An ICE-related protease is involved in regulating programmed cell death, which may be the reason why formation of K -permissive pores by alpha-toxin in human T-lymphoctes causes apoptosis (Jonas et a/., 1994). Both apoptosis and ICE-activation are inhibited when alpha-toxin treated cells are suspended in K" -rich medium. It is of interest that simultaneous flooding of cells with Ca , such as occurs when larger pores are formed in lymphocytes (e.g. at high alpha-toxin concentrations or with . coli hemolysin) counteracts the apoptosis-promoting effect of K -efflux (Jonas et a/., 1994). 

Other virulence factors include the production of hemolysin and aerobactin. Hemolysin is a cytotoxic protein produced by bacteria that lyses a wide range of cells, including erythrocytes, PMNs, and monocytes. coli and other gram-negative bacteria require iron for aerobic metabohsm and multiplication. Aerobactin facilitates the binding and uptake of iron by E. coli however, the significance of this property in the pathogenesis of UTIs remains unknown. 

FIGURE 11-13 Membrane proteins with -barrel structure. Five examples are shown, viewed in the plane of the membrane The first four are from the E. coli outer membrane. FepA (PDB ID 1 FEP), involved in iron uptake, has 22 membrane-spanning /3 strands. OmpLA (derived from PDB ID 1 QD5), a phospholipase, is a 12-stranded /3 barrel that exists as a dimer in the membrane. Maltoporin (derived from PDB ID 1 MAL), a maltose transporter, is a trimer, each monomer constructed of 1 6 /3 strands. TolC (PDB ID 1 EK9), another transporter, has three separate subunits, each contributing four /3 strands in this 12-stranded barrel. The Staphylococcus aureus a-hemolysin toxin (PDB ID 7AHL top view below) is composed of seven identical subunits, each contributing one hairpin-shaped pair of /3 strands to the 14-stranded barrel. 

Gentschev I, Dietrich G, Goebel W (2002). The E. coli alpha-hemolysin secretion system and its use in vaccine development. Trends Microbiol. 10 39-45. 

Kreft J, Berger H, Haertlein M, Mueller B, Goebel G, Weidinger W (1983) Qoning and expression in E. coli and Bacillus subtilis of the hemolysin determinant from Bacillus cereus. J Bacteriol 155 681-689 Lapidot A, Mechaly A, Shoham Y (1996) Overexpression and single-step purification of a thermostable xylanase from Bacillus stearothermophilus T-6. J Biotechnol 51 259-264... 

Strains of other K serotypes do not contain significant amounts of sialic acids (Barry et al., 1962 Barry, 1959). Interestingly, there is no serological relationship between E, coli of the K serotypes and other bacteria of O serotype (Barry et aL, 1962 Kedzierska et aL, 1968). Furthermore, the existence of sialic acids in E, coli, in contrast to bacteria of O serotype, is not related to the presence of bacteriocine or hemolysin (Barry, 1959). 

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