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Structure and function of RTX toxins of Gram-negative bacteria
Zhuk, Karyna ; Osička, Radim (advisor) ; Šulc, Miroslav (referee)
RTX toxins (Repeats in ToXin) are produced by Gram-negative bacteria, most of which are important human or animal pathogens. The polypeptide chain of each RTX toxin consists of four conserved regions. An N-terminal hydrophobic domain, which is important for insertion of the RTX toxin into the host cell membrane and pore formation. The hydrophobic domain is followed by an acylated segment containing conserved lysine residues, at which the toxin is acylated and thus activated. The C-terminal portion of each RTX toxin contains a repeat domain to which calcium ions bind. The C-terminus of the toxin contains a secretion signal that is recognized by the type I secretion system, which transports the toxin from the bacterial cytosol to the external environment. After secretion, RTX toxins interact with the cell surface via specific β2 integrins and/or glycosylated structures such as glycoproteins and gangliosides or membrane components such as sphingomyelins and cholesterol. Once bound to the cell, RTX toxin monomers insert into the membrane and oligomerize to form pores. The uncontrolled flow of ions through these pores can lead to disruption of bactericidal functions of myeloid phagocytes, stimulation or suppression of the release of pro-inflammatory cytokines, modulation of various signaling and...
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