hlyA

HlyA, short for alpha-hemolysin A, refers to a secreted cytolytic toxin produced by certain strains of Escherichia coli and other Gram-negative bacteria. It is a pore-forming toxin that contributes to the damage of host cells and tissues during infection. In pathogenic E. coli, HlyA is commonly associated with extraintestinal pathogenic strains and can play a role in urinary tract infections, neonatal meningitis, and sepsis by promoting cell lysis and inflammation.

Genetic organization and secretion

The hlyA gene is typically part of the hlyCABD operon. The operon encodes the toxin (HlyA) along with components of a Type I secretion system: HlyB (an ATP-binding cassette transporter), HlyD (a membrane fusion protein), and TolC (an outer membrane channel). The toxin is produced as an inactive pro-toxin and requires post-translational activation by the acyltransferase HlyC, which acylates specific lysine residues on HlyA. This acylation is essential for the toxin’s activity and its ability to form pores in target cell membranes. The secretion system transports HlyA directly from the cytoplasm to the extracellular environment, bypassing the periplasm.

Mode of action

Activated HlyA binds to target cell membranes and assembles into pore-forming oligomers, disrupt­ing membrane integrity, causing ion flux, cellular damage, and lysis. The toxin can induce hemolysis on blood agar and contribute to cytotoxic effects on leukocytes and other host cells. The exact receptor interactions are not fully defined but involve lipid components of the plasma membrane.

Clinical relevance

HlyA is a virulence factor in pathogenic E. coli and is used as a marker of virulence potential in some diagnostic and research contexts. Its activity is an example of how bacterial toxins can facilitate tissue damage and inflammatory responses during infection.