Locus of enterocyte effacement

Locus of enterocyte effacement (LEE) is a pathogenicity island found in certain strains of Escherichia coli (E. coli), such as enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC). This genomic island is responsible for the formation of attaching and effacing (A/E) lesions on the intestinal epithelium, a hallmark of infection by these pathogens. The LEE encodes a type III secretion system (T3SS), effector proteins, a regulator, and intimin, a protein crucial for the intimate attachment of the bacteria to the host cell surface.

Genetic Organization

The LEE pathogenicity island is approximately 35-43 kilobase pairs in length and is organized into five major operons (LEE1 to LEE5). These operons encode for components of the T3SS, a needle-like structure used by the bacteria to inject effector proteins directly into the host cell. The effector proteins manipulate host cell processes to the advantage of the bacteria. The LEE also encodes for intimin (encoded by the eae gene), which is essential for the intimate adherence of the bacteria to the enterocytes and the formation of A/E lesions.

Pathogenesis

Upon infection, EPEC and EHEC utilize the T3SS to inject a variety of effector proteins into the host cell. These effectors disrupt normal cell function, leading to the effacement of microvilli and the rearrangement of the host cell's actin cytoskeleton to form pedestal-like structures on which the bacteria adhere. The intimate attachment is mediated by intimin, which binds to its translocated receptor (Tir), itself injected into host cells by the bacteria. This interaction is crucial for the formation of A/E lesions, characterized by the loss of microvilli and the intimate attachment of the bacteria to the enterocyte surface.

Clinical Significance

Infections with EPEC and EHEC are significant causes of diarrheal illnesses in both developing and developed countries. EPEC is a leading cause of infantile diarrhea in developing countries, while EHEC, particularly serotype O157:H7, is associated with outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) in developed countries. The presence of the LEE pathogenicity island is a key virulence factor for these strains, and understanding its function is crucial for the development of therapeutic and preventive measures against EPEC and EHEC infections.

Research and Treatment

Research into the LEE and its associated virulence factors has led to the development of potential therapeutic targets, including inhibitors of the T3SS and vaccines targeting intimin. However, the treatment of infections caused by EPEC and EHEC remains primarily supportive, with hydration and, in some cases, antimicrobial therapy. The emergence of antibiotic resistance in these pathogens underscores the need for continued research and the development of novel therapeutic strategies.

See Also

• Enteropathogenic Escherichia coli
• Enterohemorrhagic Escherichia coli
• Type III secretion system
• Hemolytic uremic syndrome