Actin enhances the haemolytic activity of Escherichia coli

Abstract

Actin is a major cytoskeletal protein of mammalian muscle and non-muscle cells. Exposure of cells to soluble factors that damage cell membranes results in the release of actin into the extracellular spaces. The a-haemolysin (HlyA) of Escherichia coli is the prototype RTX (repeat in toxin) toxin and is thought t o be important in virulence because of its ability to lyse cells by formation of pores in the cell membrane. These studies were conducted to determine if actin influences growth and haemolytic activity of E. coli. Growth of E. coli in the presence of actin resulted in culture supernatant haemolytic activity that was 2.4-,27-and 33-fold greater than that of E. coli grown in medium containing BSA, non-supplemented medium, or medium containing heatdenatured actin, respectively. The enhanced haemolytic activity occurred only when actin was present during the growth phase and there was no effect when actin was added to culture Supernatants containing haemolysin. The increased haemolytic activity by actin was concentration-dependent, detectable in early-exponential-phase growth, and associated with increased concentrations of secreted HlyA by Western blotting. Actin induced a 29-fold increase in alkaline phosphatase activity in f. coli CC118 with a TnphoA insertion in the hlyB determinant of the recombinant haemolysin plasmid pWAM04. These results indicate that extracellular actin enhances haemolysin production by Em coli and may have implications in the pathogenesis of E. coli infections.

Plasma Gelsolin: Function, Prognostic Value, and Potential Therapeutic Use

“…The actin scavenger hypothesis was supported by evidence that extracellular actin was toxic to rats [81] and actin-containing sera were toxic to endothelial cells [82], and that actin-binding proteins inhibited the toxic effects. Extracellular actin, by promoting alpha hemolysin (HlyA) production, may also enhance the severity of Escherichia coli infections, suggesting F-actin involvement in pathogenic mechanisms at infection sites [83]. The high viscosity of actin filaments, the inhibitory effect of actin on fibrinolysis [84], and the fact that actin binds adenine nucleotides that could activate purinergic receptors [85] were mechanisms invoked for possible secondary tissue damage.…”

Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

“…Actin is present in high concentrations in most eukaryotic cells, constituting more than 10% of the cellular protein [ 18 , 19 ]. The release of actin into systemic circulation in response to injury or illness-associated necrosis results in adverse pathophysiologic consequences including (i) increase of blood viscosity and disturbances in microvascular flow, (ii) activation of platelets with resulting platelet aggregation, (iii) microvascular thrombosis, (iv) release of proinflammatory mediators such as thromboxane, (v) impairment of fibrinolysis, (vi) promotion of alpha-haemolysin (HlyA) production, exacerbating Escherichia coli infections, and (vii) binding of adenine nucleotides that could activate purigenic receptors [ 19 , 20 , 21 , 22 , 23 , 24 ]. Thus, actin exposure resulting from primary injury can lead to the development of secondary tissue injury due to the high toxicity of actin.…”

Human Serum Albumin Enhances the Hemolytic Activity of Vibrio vulnificus

“…The extracellular actin is known to enhance the activities of E. coli hemolysin and P. haemolytica leukotoxin and to be implicated in the pathogenesis of E. coli and P. haemolytica infections. 25,26) Fig. 3.…”