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The effector repertoire of enteropathogenic E. coli: ganging up on the host cell.

Dean P, Kenny B - Curr. Opin. Microbiol. (2009)

Bottom Line: More recently, effectors encoded outside the LEE (non-LEE effectors) have been discovered and their functions are beginning to be uncovered.The recent completion of the EPEC genome sequence suggests its effector repertoire consists of at least 21 effector proteins.Here, we describe the genomic location of effectors and discuss recent advances made on effector cellular function as well as their role in the infection process.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. p.dean@ncl.ac.uk

ABSTRACT
Diarrhoeal disease caused by enteropathogenic E. coli (EPEC) is dependent on a delivery system that injects numerous bacterial 'effector' proteins directly into host cells. The best-described EPEC effectors are encoded together on the locus of enterocyte effacement (LEE) pathogenicity island and display high levels of multifunctionality and cooperativity within the host cell. More recently, effectors encoded outside the LEE (non-LEE effectors) have been discovered and their functions are beginning to be uncovered. The recent completion of the EPEC genome sequence suggests its effector repertoire consists of at least 21 effector proteins. Here, we describe the genomic location of effectors and discuss recent advances made on effector cellular function as well as their role in the infection process.

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The modular nature of multifunctional LEE effector proteins. Tir, Map and EspF are the best-studied EPEC effectors and have been implicated in subverting multiple cellular processes. These proteins possess many eukaryotic-like motifs with many being assigned to elicit specific host cellular responses. Only those motifs/domains with proven and documented functions within the host cell are shown whilst chaperone binding sites or the N-terminal bacterial secretion and translocation signals are not shown. Other EPEC effectors are not shown because of the paucity of information regarding their functional domains. See text for abbreviations.
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fig2: The modular nature of multifunctional LEE effector proteins. Tir, Map and EspF are the best-studied EPEC effectors and have been implicated in subverting multiple cellular processes. These proteins possess many eukaryotic-like motifs with many being assigned to elicit specific host cellular responses. Only those motifs/domains with proven and documented functions within the host cell are shown whilst chaperone binding sites or the N-terminal bacterial secretion and translocation signals are not shown. Other EPEC effectors are not shown because of the paucity of information regarding their functional domains. See text for abbreviations.

Mentions: In addition to their cooperative nature, the LEE effectors are strikingly multifunctional (Table 1) binding a large number of eukaryotic proteins and targeting various host cell compartments (Table 1 and Figure 1). This is best exemplified by EspF which localises to multiple cellular compartments (including cytoplasm, mitochondria, apical and lateral membranes) and interacts with at least 12 reported host proteins, with its delivery linked to mitochondrial dysfunction, microvilli effacement, TJ disruption, apoptosis, epithelial transporter inhibition, anti-phagocytosis, membrane remodelling and actin-pedestal maturation [15,16,18–22,26,51–53]. Like other LEE effectors, the modular construction of EspF facilitates its multifunctional behaviour (Figure 2), with specific motifs inducing distinct cellular responses, such as an N-terminal mitochondrial targeting sequence (MTS) linked to mitochondria dysfunction and apoptosis [15,21], whilst proline-rich repeats, that include src homology 3 (SH3)-binding domains, recruit sorting nexin 9 (SNX9) causing membrane remodelling ([22]; Table 1 and Figure 2). EspF, like its EHEC homologues EspF and EspFU/Tccp, recruits N-WASP (a key regulator of actin polymerisation), with studies on EspFU revealing it specifically activates N-WASP by mimicking an internal regulatory element [23,24]. Finally, although EspF plays an essential role in anti-phagocytosis, EspB–myosin interaction has recently been reported to inhibit both phagocytosis and microvilli effacement [25•]. However, as both of these bacterial processes can occur with EspB/EspF-positive but not EspB-positive/EspF-negative strains [19•,26]; this suggests that EspB is neither solely responsible nor sufficient.


The effector repertoire of enteropathogenic E. coli: ganging up on the host cell.

Dean P, Kenny B - Curr. Opin. Microbiol. (2009)

The modular nature of multifunctional LEE effector proteins. Tir, Map and EspF are the best-studied EPEC effectors and have been implicated in subverting multiple cellular processes. These proteins possess many eukaryotic-like motifs with many being assigned to elicit specific host cellular responses. Only those motifs/domains with proven and documented functions within the host cell are shown whilst chaperone binding sites or the N-terminal bacterial secretion and translocation signals are not shown. Other EPEC effectors are not shown because of the paucity of information regarding their functional domains. See text for abbreviations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2697328&req=5

fig2: The modular nature of multifunctional LEE effector proteins. Tir, Map and EspF are the best-studied EPEC effectors and have been implicated in subverting multiple cellular processes. These proteins possess many eukaryotic-like motifs with many being assigned to elicit specific host cellular responses. Only those motifs/domains with proven and documented functions within the host cell are shown whilst chaperone binding sites or the N-terminal bacterial secretion and translocation signals are not shown. Other EPEC effectors are not shown because of the paucity of information regarding their functional domains. See text for abbreviations.
Mentions: In addition to their cooperative nature, the LEE effectors are strikingly multifunctional (Table 1) binding a large number of eukaryotic proteins and targeting various host cell compartments (Table 1 and Figure 1). This is best exemplified by EspF which localises to multiple cellular compartments (including cytoplasm, mitochondria, apical and lateral membranes) and interacts with at least 12 reported host proteins, with its delivery linked to mitochondrial dysfunction, microvilli effacement, TJ disruption, apoptosis, epithelial transporter inhibition, anti-phagocytosis, membrane remodelling and actin-pedestal maturation [15,16,18–22,26,51–53]. Like other LEE effectors, the modular construction of EspF facilitates its multifunctional behaviour (Figure 2), with specific motifs inducing distinct cellular responses, such as an N-terminal mitochondrial targeting sequence (MTS) linked to mitochondria dysfunction and apoptosis [15,21], whilst proline-rich repeats, that include src homology 3 (SH3)-binding domains, recruit sorting nexin 9 (SNX9) causing membrane remodelling ([22]; Table 1 and Figure 2). EspF, like its EHEC homologues EspF and EspFU/Tccp, recruits N-WASP (a key regulator of actin polymerisation), with studies on EspFU revealing it specifically activates N-WASP by mimicking an internal regulatory element [23,24]. Finally, although EspF plays an essential role in anti-phagocytosis, EspB–myosin interaction has recently been reported to inhibit both phagocytosis and microvilli effacement [25•]. However, as both of these bacterial processes can occur with EspB/EspF-positive but not EspB-positive/EspF-negative strains [19•,26]; this suggests that EspB is neither solely responsible nor sufficient.

Bottom Line: More recently, effectors encoded outside the LEE (non-LEE effectors) have been discovered and their functions are beginning to be uncovered.The recent completion of the EPEC genome sequence suggests its effector repertoire consists of at least 21 effector proteins.Here, we describe the genomic location of effectors and discuss recent advances made on effector cellular function as well as their role in the infection process.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. p.dean@ncl.ac.uk

ABSTRACT
Diarrhoeal disease caused by enteropathogenic E. coli (EPEC) is dependent on a delivery system that injects numerous bacterial 'effector' proteins directly into host cells. The best-described EPEC effectors are encoded together on the locus of enterocyte effacement (LEE) pathogenicity island and display high levels of multifunctionality and cooperativity within the host cell. More recently, effectors encoded outside the LEE (non-LEE effectors) have been discovered and their functions are beginning to be uncovered. The recent completion of the EPEC genome sequence suggests its effector repertoire consists of at least 21 effector proteins. Here, we describe the genomic location of effectors and discuss recent advances made on effector cellular function as well as their role in the infection process.

Show MeSH
Related in: MedlinePlus