In spite of advances in surgical techniques, critical care facilities, diagnostic capacities, and improvements in antimicrobial therapy, the mortality from intraabdominal infection remains high. A recent experience from five university intensive care units reported an overall mortality of 28% from intraabdominal infection. The magnitude of the clinical problem necessitates continued basic research. The peritoneal cavity possesses a remarkable capacity to combat infection. Surgical predecessors have laid the groundwork of defining the mechanics whereby this region of the body handles infection. These are typically described as: a) rapid dispersal of particulate matter (including bacteria) via diaphragmatic lymphatics lacunae; b) rapid upregulation of phagocytic capacity within the peritoneum within 2-6 hours after bacterial introduction; and c) mechanical sequestration of bacteria by fibrin trapping and obliteration of dead space by paralytic ileus. An important consideration missing from the majority of these studies is the alteration in outcome predicated upon rapid adaptive changes of the infecting organisms. All bacteria do not possess the same ability to produce infection and many can undergo significant phenotypic changes in different environments.
The specific aim of this proposal is to understand how the most frequently recovered bacteria from intraabdominal infection, Escherichia coli, evolves during peritoneal infection. These organisms are not inert, but actively change their metabolic pathways and physical properties to survive in a hostile environment. The goals of the project are to determine: 1) the intraperitoneal kinetics of varying wild types and laboratory strains of E. coli, and correlate known virulence traits (O and K antigens, alpha-hemolysin production, ability to adhere to mammalian cells, and the expression of outer membrane proteins) to survivability within the peritoneum. 2) the effect of adjuvants of intraperitoneal infection (hemoglobin, bile salts, stool, mucin) upon the infectivity of E. coli and correlation with virulence. 3) the traits of E. coli which promote mixed infections: in particular with the most common anaerobe, Bacteroides fragilis. An improved prognosis for patients with intraabdominal infection will occur when physicians understand not only the manner in which the host defenses interact with infecting organisms, but also the adaptive mechanisms employed by the bacteria to survive within the host peritoneum. It is the purpose of this proposal to begin the process of delineating these mechanisms.
| May, A K; Gleason, T G; Sawyer, R G et al. (2000) Contribution of Escherichia coli alpha-hemolysin to bacterial virulence and to intraperitoneal alterations in peritonitis. Infect Immun 68:176-83 |
| May, A K; Sawyer, R G; Gleason, T et al. (1996) In vivo cytokine response to Escherichia coli alpha-hemolysin determined with genetically engineered hemolytic and nonhemolytic E. coli variants. Infect Immun 64:2167-71 |
