Hierarchical Delivery of an Essential Host Colonization Factor in Enteropathogenic Escherichia coli

Many significant bacterial pathogens use a type III secretion system to inject effector proteins into host cells to disrupt specific cellular functions, enabling disease progression. The injection of these effectors into host cells is often dependent on dedicated chaperones within the bacterial cell. In this report, we demonstrate that the enteropathogenic Escherichia coli (EPEC) chaperone CesT interacts with a variety of known and putative type III effector proteins. Using pull-down and secretion assays, a degenerate CesT binding domain was identified within multiple type III effectors. Domain exchange experiments between selected type III effector proteins revealed a modular nature for the CesT binding domain, as demonstrated by secretion, chaperone binding, and infection assays. The CesT-interacting type III effector Tir, which is crucial for in vivo intestinal colonization, had to be expressed and secreted for efficient secretion of other type III effectors. In contrast, the absence of other CesT-interacting type III effectors did not abrogate effector secretion, indicating an unexpected hierarchy with respect to Tir for type III effector delivery. Coordinating the expression of other type III effectors with cesT in the absence of tir partially restored total type III effector secretion, thereby implicating CesT in secretion events. Collectively, the results suggest a coordinated mechanism involving both Tir and CesT for type III effector injection into host cells. Many significant bacterial pathogens use a type III secretion system to inject effector proteins into host cells to disrupt specific cellular functions, enabling disease progression. The injection of these effectors into host cells is often dependent on dedicated chaperones within the bacterial cell. In this report, we demonstrate that the enteropathogenic Escherichia coli (EPEC) chaperone CesT interacts with a variety of known and putative type III effector proteins. Using pull-down and secretion assays, a degenerate CesT binding domain was identified within multiple type III effectors. Domain exchange experiments between selected type III effector proteins revealed a modular nature for the CesT binding domain, as demonstrated by secretion, chaperone binding, and infection assays. The CesT-interacting type III effector Tir, which is crucial for in vivo intestinal colonization, had to be expressed and secreted for efficient secretion of other type III effectors. In contrast, the absence of other CesT-interacting type III effectors did not abrogate effector secretion, indicating an unexpected hierarchy with respect to Tir for type III effector delivery. Coordinating the expression of other type III effectors with cesT in the absence of tir partially restored total type III effector secretion, thereby implicating CesT in secretion events. Collectively, the results suggest a coordinated mechanism involving both Tir and CesT for type III effector injection into host cells. Bacterial pathogens often have multiple systems to disrupt and subvert host cellular processes that are involved in disease production. One such system is the type III secretion system (T3SS) 4The abbreviations used are:T3SStype III secretion systemEPECenteropathogenic E. coliA/Eattaching and effacingLEElocus of enterocyte effacementCBDCesT binding domainaaamino acidsGSTglutathione S-transferase. that is widespread among Gram-negative pathogens of animals and plants. T3SSs are composed of multiprotein complexes in the bacterial membrane that mediate the rapid injection of type III effector proteins directly into host cells (1Ghosh P. Microbiol. Mol. Biol. Rev. 2004; 68: 771-795Crossref PubMed Scopus (327) Google Scholar). type III secretion system enteropathogenic E. coli attaching and effacing locus of enterocyte effacement CesT binding domain amino acids glutathione S-transferase. Enteropathogenic Escherichia coli (EPEC) is a human diarrheal attaching and effacing (A/E) pathogen that attaches to intestinal microvilli and then injects type III effector proteins directly into host cells (2Kaper J.B. Nataro J.P. Mobley H.L. Nat. Rev. Microbiol. 2004; 2: 123-140Crossref PubMed Scopus (3464) Google Scholar, 3Dean P. Maresca M. Kenny B. Curr. Opin. Microbiol. 2005; 8: 28-34Crossref PubMed Scopus (65) Google Scholar). After bacterial attachment, dramatic cytoskeletal rearrangements result in the effacement of microvilli (4Caron E. Crepin V.F. Simpson N. Knutton S. Garmendia J. Frankel G. Curr. Opin. Microbiol. 2006; 9: 40-45Crossref PubMed Scopus (93) Google Scholar). The A/E phenotype has been linked to the locus of enterocyte effacement (LEE) (5Jerse A.E. Yu J. Tall B.D. Kaper J.B. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 7839-7843Crossref PubMed Scopus (934) Google Scholar), a pathogenicity island that is involved in EPEC virulence (6Elliott S.J. Wainwright L.A. McDaniel T.K. Jarvis K.G. Deng Y.K. Lai L.C. McNamara B.P. Donnenberg M.S. Kaper J.B. Mol. Microbiol. 1998; 28: 1-4Crossref PubMed Scopus (552) Google Scholar). The LEE encodes components of the T3SS, transcriptional regulators, chaperones and type III effector proteins, the latter of which are translocated directly into host cells (7Deng W. Puente J.L. Gruenheid S. Li Y. Vallance B.A. Vazquez A. Barba J. Ibarra J.A. O'Donnell P. Metalnikov P. Ashman K. Lee S. Goode D. Pawson T. Finlay B.B. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 3597-3602Crossref PubMed Scopus (508) Google Scholar). EPEC and other related strains have multiple type III effectors that are encoded within the LEE, in addition to non-LEE-encoded effectors that are located in distinct pathogenicity islands throughout the chromosome (3Dean P. Maresca M. Kenny B. Curr. Opin. Microbiol. 2005; 8: 28-34Crossref PubMed Scopus (65) Google Scholar, 8Garmendia J. Frankel G. Crepin V.F. Infect. Immun. 2005; 73: 2573-2585Crossref PubMed Scopus (304) Google Scholar, 9Tobe T. Beatson S.A. Taniguchi H. Abe H. Bailey C.M. Fivian A. Younis R. Matthews S. Marches O. Frankel G. Hayashi T. Pallen M.J. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 14941-14946Crossref PubMed Scopus (356) Google Scholar). One of the best studied EPEC type III effectors is Tir (translocated intimin receptor), a protein that is injected into host cells, modified by host kinases, and localized to the host membrane (10Kenny B. DeVinney R. Stein M. Reinscheid D.J. Frey E.A. Finlay B.B. Cell. 1997; 91: 511-520Abstract Full Text Full Text PDF PubMed Scopus (1003) Google Scholar, 11Phillips N. Hayward R.D. Koronakis V. Nat. Cell Biol. 2004; 6: 618-625Crossref PubMed Scopus (106) Google Scholar). Furthermore, the amino- and carboxyl-terminal regions of Tir interact with a number of host proteins, causing dramatic host cytoskeletal rearrangements, which result in actin-rich lesions termed pedestals (12Gruenheid S. DeVinney R. Bladt F. Goosney D. Gelkop S. Gish G.D. Pawson T. Finlay B.B. Nat. Cell Biol. 2001; 3: 856-859Crossref PubMed Scopus (299) Google Scholar, 13Campellone K.G. Giese A. Tipper D.J. Leong J.M. Mol. Microbiol. 2002; PubMed Scopus Google Scholar, M. J. A. N. J. Knutton S. Frankel G. 2004; PubMed Scopus Google Scholar, A. N. M. T. Frankel G. Cell Microbiol. 2006; 8: PubMed Scopus Google Scholar, DeVinney R. Frey E.A. Finlay B.B. Curr. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). host Tir as a for EPEC intimin (10Kenny B. DeVinney R. Stein M. Reinscheid D.J. Frey E.A. Finlay B.B. Cell. 1997; 91: 511-520Abstract Full Text Full Text PDF PubMed Scopus (1003) Google Scholar), a bacterial membrane encoded by the LEE of A/E The of Tir in the virulence of A/E pathogens has been demonstrated in in vivo of tir not the host of disease (7Deng W. Puente J.L. Gruenheid S. Li Y. Vallance B.A. Vazquez A. Barba J. Ibarra J.A. O'Donnell P. Metalnikov P. Ashman K. Lee S. Goode D. Pawson T. Finlay B.B. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 3597-3602Crossref PubMed Scopus (508) Google Scholar, O. J.P. S. J. G. P. M. J. A. E. Infect. Immun. 68: PubMed Scopus Google Scholar, J.M. C.M. Infect. Immun. PubMed Scopus Google Scholar). studied LEE encoded type III effectors and J.P. Donnenberg M.S. Cell Microbiol. 2004; 6: PubMed Scopus Google Scholar, B. S. J. H. Mol. Microbiol. 2002; PubMed Scopus Google Scholar, M. Kaper J.B. G. Mol. Microbiol. 2005; PubMed Scopus (93) Google Scholar, T. A. S. Abe A. J. 2004; PubMed Scopus Google Scholar), which have been to have within host cells. The of type III effectors into host cells is often dependent on a dedicated of proteins termed type III chaperones domain proteins are and Curr. Opin. Microbiol. 6: PubMed Scopus Google Scholar). III secretion chaperones that to the of effectors and in the bacterial of effectors into the host cell. The of type III secretion chaperones have been in a with an effector A. J. 2004; PubMed Scopus Google Scholar, Y. Frey E.A. D. F. Finlay B.B. Nat. Biol. 2001; 8: PubMed Scopus Google Scholar, M. M. Mol. Cell. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar, 2001; PubMed Scopus Google Scholar, P. Mol. Cell. 2002; 9: Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. 2004; PubMed Scopus Google Scholar). Collectively, these have revealed chaperone in the absence of type III secretion chaperones are to a have been demonstrated to have and In the of the LEE encoded type III secretion chaperone CesT was to and Tir within the bacterial A. M. R. Puente J.L. Finlay B.B. Mol. Microbiol. PubMed Scopus Google Scholar, S.J. M.S. J.L. Wainwright L.A. M. Frankel G. Knutton S. Kaper J.B. Mol. Microbiol. PubMed Scopus Google have demonstrated with the effectors and E.A. Kenny B. Knutton S. Frankel G. Mol. Microbiol. PubMed Scopus Google Scholar, N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar, E.A. S.J. Frankel G. PubMed Scopus Google Scholar). CesT is for the efficient in type III secretion of other LEE and type III effectors N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar), that other within the Furthermore, we have demonstrated that CesT interacts with the of the T3SS, in a to and type III effectors for into host cells N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar, A. Finlay B.B. J. PubMed Scopus Google Scholar). cesT not disease in a of attaching and effacing (7Deng W. Puente J.L. Gruenheid S. Li Y. Vallance B.A. Vazquez A. Barba J. Ibarra J.A. O'Donnell P. Metalnikov P. Ashman K. Lee S. Goode D. Pawson T. Finlay B.B. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 3597-3602Crossref PubMed Scopus (508) Google Scholar), indicating that this type III secretion chaperone has a in In this we demonstrate that CesT interacts with EPEC type III effectors. degenerate CesT binding domain within multiple type III effectors was identified and by pull-down and protein variety of and used to demonstrate a modular nature for the CesT binding multiple EPEC strains in secretion and infection assays, is demonstrated that a coordinated is for the efficient injection of other type III effectors into host cells. The results to the injection of the host Tir, which the of effectors. Bacterial and S. PubMed Scopus Google and strains used for experiments in of of of and then into modified E. coli as a and E. coli was used as an for selected and used in this type S. PubMed Scopus Google B. DeVinney R. Stein M. Reinscheid D.J. Frey E.A. Finlay B.B. Cell. 1997; 91: 511-520Abstract Full Text Full Text PDF PubMed Scopus (1003) Google of W. Li Y. Frey E.A. Lee S. Gruenheid S. Puente J.L. Finlay B.B. Infect. Immun. 2005; 73: PubMed Scopus Google N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google coli host for of E. coli for N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google in A. M. R. Puente J.L. Finlay B.B. Mol. Microbiol. PubMed Scopus Google Tir A. M. R. Puente J.L. Finlay B.B. Mol. Microbiol. PubMed Scopus Google EPEC W. Li Y. Frey E.A. Lee S. Gruenheid S. Puente J.L. Finlay B.B. Infect. Immun. 2005; 73: PubMed Scopus Google EPEC A. M. R. Puente J.L. Finlay B.B. Mol. Microbiol. PubMed Scopus Google EPEC Tir a tir N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google as a into encodes an and as a encodes in to the in to the in to the in to the in to the in to the in Tir such that the is with the in such that the is with the Tir in the tir in to the tir in the in in in a and was in a and The was with and and into the of to an in with a the The encodes the of a for expression and used in a with The of the and the The was with by into to which the of by as in a with with and The with and into of the the CesT binding domain of was a an was with and was then with and The with and then in a by the addition of of the was to a with and to a that was then with by into to The of exchange of Tir and used a multiple the as The was with and as of tir was by EPEC with and and with and then to other in a The then as in a with and The and of tir then EPEC with and D. and and as The then as a in a with and a that was with and into to the the Tir was with and E. of was with and as F. The and then The as in a with and which a that was into the tir was by a with and in a with as by of the into to The used in a with as to the tir a was by a EPEC with and by into to a Tir an was and used in a with as The was with by and into The was then into for in was by exchange with a with an and used to a EPEC and a The with and with The as in a with and with the into was into EPEC by the and of as S. Deng W. O'Donnell P. Goode D. Li Y. Frey E.A. Metalnikov P. Pawson T. Ashman K. Finlay B.B. Mol. Microbiol. 2004; PubMed Scopus Google Scholar). a was and and and by the of EPEC was in the by exchange a W. Li Y. Frey E.A. Lee S. Gruenheid S. Puente J.L. Finlay B.B. Infect. Immun. 2005; 73: PubMed Scopus Google a of with an by and protein secretion was of the within The was into EPEC strains and in transcriptional as E. Puente J.L. J. 2001; PubMed Scopus Google Scholar). of EPEC EPEC secreted proteins as N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar). modified EPEC cells and the was then The was by the addition of and on for The proteins by and then with proteins in and to and CesT and CesT was by an E. coli N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar). CesT was with binding by the addition of EPEC The was with binding by a proteins with of CesT-interacting proteins, the was modified to CesT the CesT-interacting EPEC proteins the was with binding to and proteins the The was then a with binding to The this was then by a between and expressed in was a as N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar). was to the by The then with of was the of The protein was then to and for demonstrated that did not to to a CesT with the proteins In Cell EPEC cells with EPEC strains a of infection of for in modified with by with The for as S. Deng W. O'Donnell P. Goode D. Li Y. Frey E.A. Metalnikov P. Pawson T. Ashman K. Finlay B.B. Mol. Microbiol. 2004; PubMed Scopus Google Scholar). used to and by and with of was with the a a with an and of a EPEC secreted protein was to a CesT proteins and as The proteins and in by protein regions within the to to and a as by the The on an the of of The D.J. PubMed Scopus Google Scholar), and within the the In to within the EPEC the CesT with III on in is known to interact with effector proteins, Tir, and A. M. R. Puente J.L. Finlay B.B. Mol. Microbiol. PubMed Scopus Google Scholar, S.J. M.S. J.L. Wainwright L.A. M. Frankel G. Knutton S. Kaper J.B. Mol. Microbiol. PubMed Scopus Google Scholar, E.A. Kenny B. Knutton S. Frankel G. Mol. Microbiol. PubMed Scopus Google Scholar, N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar, E.A. S.J. Frankel G. PubMed Scopus Google Scholar). we demonstrated that the efficient secretion of other EPEC type III effector proteins CesT E.A. Kenny B. Knutton S. Frankel G. Mol. Microbiol. PubMed Scopus Google Scholar, N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar), a of these proteins with CesT type III effector proteins, we of a of EPEC that is known to type III effector proteins not proteins W. Li Y. Frey E.A. Lee S. Gruenheid S. Puente J.L. Finlay B.B. Infect. Immun. 2005; 73: PubMed Scopus Google Scholar). was that type III effector secretion, and the was and a CesT After protein and to Tir was the indicating a with CesT was in the as as other protein for type III secretion to the absence of the did not known type III effectors and as a on a CesT CesT did not proteins to significant not a type secreted protein J.L. F. J. Nataro J.P. Kaper J.B. Infect. Immun. 2001; PubMed Scopus Google Scholar), was not to significant the indicating the of the for CesT of proteins the identified known CesT binding Tir, and other type III effectors and identified as CesT-interacting proteins. proteins are known to be of the type III secretion and CesT for efficient secretion in EPEC N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar). with the CesT is with on CesT for efficient The effectors are encoded in pathogenicity islands within EPEC implicating CesT as a chaperone for type III effector proteins identified in a of the CesT Domain of of multiple type III effectors on the CesT be by III effector between proteins. the that CesT to proteins, was expressed a in E. coli that not EPEC type III effectors. be expressed as a protein in the absence of which was not the for type III effectors was a and then with A. M. R. Puente J.L. Finlay B.B. Mol. Microbiol. PubMed Scopus Google Scholar), by and with with did not to the we to the CesT with was expressed in and for protein was secreted in to a in as demonstrated by total secreted protein the of CesT for efficient secretion of and a then expressed in to the type III secretion of of the strains had secretion was not in secreted protein the secreted The was not and the protein in the bacterial as demonstrated by of the EPEC was and the CesT was the and The protein was with CesT indicating that the CesT binding domain of this effector within the amino Collectively, these experiments demonstrate an between CesT and the of Furthermore, the amino acids of are and to mediate secretion of this non-LEE-encoded type III effector in CesT Domain the of III of CesT to multiple type III effectors that protein has a In to this binding domain was between the type III the known of Tir was used as a to in other type III effectors. of other known and putative EPEC type III effectors by significant not the revealed an with the of and of EPEC The of the regions of other EPEC and type III effectors pathogenicity an amino that this the for these effectors The CesT Domain in and between on the protein secretion of multiple type III effectors and CesT was that the is modular in nature and to effectors for type III secretion with this the of and Tir for protein The into EPEC for of the a protein that was not secreted to the of Tir acids to in the protein secreted with type that the Tir to the type III secretion of the protein in the of Tir is located amino acids into the the of was used to amino acids of of the of Tir the with Tir dependent on the of CesT in EPEC A. M. R. Puente J.L. Finlay B.B. Mol. Microbiol. PubMed Scopus Google Scholar). The Tir protein the was and was secreted by EPEC indicating that the of to Tir and for type III secretion did not the and proteins not latter result that the secretion of the proteins dependent on a type III secretion The of protein to interact with CesT was the CesT binding The protein secreted to the CesT to Tir secreted by type EPEC The was to interact with the proteins then in an infection for to the type III effectors into cells. Tir injection into cells results in the of actin-rich pedestals that be as by the protein was and secreted in secretion assays, we the of for a tir the The a Tir did not pedestals to significant the tir pedestals and to type EPEC type EPEC a the translocated the proteins into cells and both localized to regions of experiments that the degenerate CesT binding domain is modular in nature and be between type III effectors. Tir III tir and cesT are as of a the E. Puente J.L. J. 2001; PubMed Scopus Google Scholar). The and of are among and is that the coordinated expression for the of the proteins. is known that not effector are with type III secretion are located within pathogenicity islands within the the CesT for other effectors in the absence of Tir protein The effectors that are by and an to the of Tir with respect to other type III effectors. a was and for effector total effector secretion was for the with the of the as as other type III effector proteins. The was with a Tir, which restored total effector to transcriptional on cesT of a type III effector encoded of the LEE within the LEE the did not secreted type III effector indicating that Tir protein expression is to total type III effector transcriptional to was used to the expression of this effector in EPEC expression was not in strains indicating that the absence of secretion in was not to a of III the on these was that by tir cesT the CesT protein be and that CesT as a to the secretion of other type III effectors. was that type III effector that interacts with CesT total type III effector secretion to the that expression was linked with this was expressed within a which is Tir expression by was to be secreted and partially restored the secretion of other type III effectors the tir was into the and for effector expressed the tir partially restored type III effector secretion Tir secretion was a did not effector secretion, that a coordinated III effector protein is for efficient type III effector Tir to III in of effector to total effector secretion in the be to an with other type III effectors the of Tir secretion the to these we a that a CesT-interacting Tir putative of Tir encodes the putative Tir secretion J.A. Kaper J.B. Mol. Microbiol. 2002; PubMed Scopus Google to the of the Tir of and the secreted protein revealed that the Tir was within the EPEC of an with In this Tir was secreted with type Tir this Tir did not effector secretion, of a type Tir protein restored type III effector secretion as by total secreted proteins. The Tir III amino acids of Tir with amino acids of of both proteins to the as by the domain exchange experiments The absence of a secretion within other type III with the hierarchy of Tir secretion other type III effectors to that amino acids of Tir with the putative J.A. Kaper J.B. Mol. Microbiol. 2002; PubMed Scopus Google mediate Tir secretion a that Tir to the was and in secretion assays. was to of and Tir as by of total secreted protein In Tir did not total type III effector secretion to indicating that amino acids of Tir secretion hierarchy to other type III effectors. III secretion chaperones effector proteins, rapid and efficient into host cells. is demonstrated that a degenerate protein domain in multiple EPEC type III effectors is involved in CesT the demonstrate that the coordinated of the type III effector Tir with chaperone by Tir secretion, to be a of that is for the efficient secretion of other type III effectors. is in with Tir a in vivo and for the a hierarchy for Tir other EPEC type III effectors. in bacterial is pathogens multiple virulence to a infection to intestinal is to and into the with and that the for attachment, Tir, is the type III effector in The suggest that has been then other type III effectors involved in the processes are The results are in with infection experiments of A/E pathogens is for host and disease progression. has been directly and demonstrated in of tir not the and not of disease J.M. C.M. Infect. Immun. PubMed Scopus Google tir not the and not disease W. Vallance B.A. Li Y. Puente J.L. Finlay B.B. Mol. Microbiol. PubMed Scopus Google and EPEC tir not in and not to host intestinal cells O. J.P. S. J. G. P. M. J. A. E. Infect. Immun. 68: PubMed Scopus Google Scholar). a of proteins the identified a and a E.A. S.J. Frankel G. PubMed Scopus Google to and as proteins. is to have chaperone S.J. A. Donnenberg M.S. G. Kaper J.B. Infect. Immun. 2002; PubMed Scopus Google within the the that interacts with both and results a a a putative CesT binding domain on be CesT-interacting type III effectors that not secreted within EPEC secretion in an to interact with has been that the CesT-interacting type III effector is expressed within EPEC E.A. Kenny B. Knutton S. Frankel G. Mol. Microbiol. PubMed Scopus Google Scholar), which was not in and other E.A. Kenny B. Knutton S. Frankel G. Mol. Microbiol. PubMed Scopus Google Scholar, N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar, E.A. S.J. Frankel G. PubMed Scopus Google Scholar), CesT interacts is involved in the secretion of effector to in EPEC protein between CesT and of effectors to specific binding for this chaperone of The binding of CesT with type III effectors that is a among the effectors that CesT by M. M. Mol. Cell. 2006; Full Text Full Text PDF PubMed Scopus Google that a number of type III effectors have a that type III secretion chaperones interact not to be the for of the EPEC type III effectors that interact with the are not in a for CesT experiments with EPEC is that a degenerate binding domain of amino acids is involved in CesT that EPEC has a mechanism to as in The coordinated expression of tir and cesT a protein of the CesT chaperone with Tir within the bacterial which results in efficient Tir In the absence of Tir tir CesT is and is to have a mechanism with respect to effector this by CesT in both type and tir strains secretion and with strains with CesT not that CesT not mediate type III effector that the of Tir secretion results in CesT with the is in with the membrane of CesT within a that is in the of Tir N. Deng W. Puente J. Frey E. N. Finlay B. Mol. Microbiol. 2005; PubMed Scopus Google Scholar). After Tir secretion, other effectors to which then secretion the is to a for type III effector secretion, is that and chaperone to mediate a hierarchy of secretion Mol. Microbiol. 2002; PubMed Scopus Google Scholar). to this for type III effector hierarchy was for the of the type III has been S. M. S.A. P. Y. A. J. PubMed Scopus Google Scholar). the is that type III effectors are The type III secretion chaperones to be involved with are to the and this The of secretion such as are in this multiple with type III effectors. J. for with the transcriptional

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