The EspF Effector, a Bacterial Pathogen's Swiss Army Knife

A. Holmes, S. Muhlen, Andrew Roe, Paul Dean

    Research output: Contribution to journalArticlepeer-review


    Central to the pathogenesis of many bacterial pathogens is the ability to deliver effector proteins directly into the cells of their eukaryotic host. EspF is one of many effector proteins exclusive to the attaching and effacing pathogen family that includes enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli. Work in recent years has revealed EspF to be one of the most multifunctional effector proteins known, with defined roles in several host cellular processes, including disruption of the epithelial barrier, antiphagocytosis, microvillus effacement, host membrane remodelling, modulation of the cytoskeleton, targeting and disruption of the nucleolus, intermediate filament disruption, cell invasion, mitochondrial dysfunction, apoptosis, and inhibition of several important epithelial transporters. Surprisingly, despite this high number of functions, EspF is a relatively small effector protein, and recent work has begun to decipher the molecular events that underlie its multifunctionality. This review focuses on the activities of EspF within the host cell and discusses recent findings and molecular insights relating to the virulence functions of this fascinating bacterial effector.

    Many of the world's most important diseases are caused by bacterial pathogens that deliver a large number of virulence proteins, termed effectors, into the cells of their host. One group of bacterial pathogens, the attaching and effacing (A/E) family, targets the mammalian intestinal tract, where they cause histopathological lesions on the apical surface of host enterocytes (51). A/E pathogens, which include enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and Citrobacter rodentium, remain on the surface of host cells and inject a raft of effector proteins through the bacterium's type three secretion system (T3SS). These effector proteins cause major disruption to host cell physiology, ultimately leading to diarrheal disease.

    Common to all A/E pathogens is a chromosomal pathogenicity island called the locus of enterocyte effacement (LEE), which carries many virulence genes, including the T3SS and six known effector proteins, Tir, Map, EspF, EspG, EspH, and EspZ (10). Tir is the best studied LEE effector and is known to target the host plasma membrane, where it serves as a receptor for the bacterial outer membrane protein Intimin. Tir is an essential virulence determinant (15, 31), possibly relating to its role in bacterial attachment, while a critical role for EspZ (previously known as SepZ) has also been demonstrated (15). For the remaining A/E pathogen effectors, it is widely accepted that most play a smaller, additive role in virulence, although the deletion of some effector genes has no obvious defects (25). Despite this, the biological functions of many A/E pathogen effectors have been determined in some depth, particularly those of the LEE-encoded effector EspF, which is becoming a model bacterial effector of multifunctionality, an emerging feature of effector proteins (27). Currently, EspF has the greatest number of reported functions among the A/E pathogen effectors and is one of the most multifunctional effector proteins known. Here, we review the diverse functions of EspF and discuss its role in disease processes in light of recent findings.
    Original languageEnglish
    Pages (from-to)4445-4453
    JournalInfection and Immunity
    Issue number11
    Publication statusPublished - 1 Nov 2010


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