Contribution of Escherichia coli Alpha-Hemolysin to Bacterial Virulence and to Intraperitoneal Alterations in Peritonitis

Abstract

Alpha-hemolysin (Hly) is a common exotoxin produced by Escherichia coli that enhances virulence in a number of clinical infections. The addition of hemolysin production to laboratory bacterial strains is known to increase the lethality of E. coli peritonitis. However, the mechanisms involved have not been determined and the contribution of hemolysin to the alterations in the host intraperitoneal environment and the leukocyte response is not known. Utilizing a rat peritonitis model, we show that wild-type hemolytic E. coli strains have a significant competitive advantage over nonhemolytic strains within the peritoneum. To examine the specific contribution of Hly to E. coli-induced virulence and alterations within the peritoneum, a mixed peritonitis model of E. coli, Bacteroides fragilis, and sterile fecal adjuvant was used. Three transformed E. coli strains were utilized: one strongly secretes active hemolysin (WAF 270), a second secretes active hemolysin but a reduced amount (WAF 260), and the third does not produce hemolysin (WAF 108). After an equal inoculum of each of the three strains, WAF 270 produced a markedly increased lethality and an increased recovery of both E. coli and B. fragilis from the host relative to the other strains. Changes in the intraperitoneal pH, degree of erythrocyte lysis, and recruitment and viability of leukocytes within the peritoneum following the induction of peritonitis differed significantly between the strongly hemolytic and nonhemolytic strains. Induction of peritonitis with WAF 270 caused a pronounced decrease in intraperitoneal pH, lysis of most of the intraperitoneal erythrocytes, and a marked decrease in recoverable viable leukocytes compared to WAF 108. Thus, hemolysin production by E. coli within the peritoneum may alter not only the host's ability to control the hemolytic strain itself but also other organisms.

Loss of Regulatory Protein RfaH Attenuates Virulence of Uropathogenic Escherichia coli

“…Alpha-hemolysin has been proven to contribute to the virulence of E. coli strains causing extraintestinal infections (17,24,43). By destroying eukaryotic cells, the toxin not only provides an opportunity for deeper invasion, but in addition supplies bacteria with nutrients liberated from host cells (e.g., iron-containing substances, such as heme).…”

Selective Activation of Human Intestinal Mast Cells by Escherichia coli Hemolysin

“…PFTs contribute to and are sometimes essential for virulence (28). The pathogenic relevance of the pore-forming toxin Hly, a member of the RTX (repeats in toxin) toxin family, has been established in animal models and in humans (29,30). E. coli Hly is produced by ϳ50% of E. coli isolates causing infections at extraintestinal locations such as the urinary tract.…”

Brief heat treatment causes a structural change and enhances cytotoxicity of theEscherichia coliα-hemolysin

“…(2) Although uropathogenic E. coli strains express several different virulence factors, those strains expressing the α-hemolysin (HLY) are more likely to be associated with disease of the upper urinary tract. (3)(4)(5)(6)(7) Increased production of HLY occurs when E. coli are grown in the presence of urine, and HLY is believed to be required for hypercolonization. (8) HLY is a member of the RTX (repeats-in-toxin) toxin family produced by a wide variety of gram-negative bacteria such as Aggregatibacter actinomycetemcomitans, Actinobacillus pleuropneumoniae, and Mannheimia haemolytica.…”