Escherichia coli type III secretion system 2 (ETT2) is widely distributed in avian pathogenic Escherichia coli isolates from Eastern China

SUMMARYPathogens utilize type III secretion systems to deliver effector proteins, which facilitate bacterial infections. The Escherichia coli type III secretion system 2 (ETT2) which plays a crucial role in bacterial virulence, is present in the majority of E. coli strains, although ETT2 has undergone widespread mutational attrition. We investigated the distribution and characteristics of ETT2 in avian pathogenic E. coli (APEC) isolates and identified five different ETT2 isoforms, including intact ETT2, in 57·6% (141/245) of the isolates. The ETT2 locus was present in the predominant APEC serotypes O78, O2 and O1. All of the ETT2 loci in the serotype O78 isolates were degenerate, whereas an intact ETT2 locus was mostly present in O1 and O2 serotype strains, which belong to phylogenetic groups B2 and D, respectively. Interestingly, a putative second type III secretion-associated locus (eip locus) was present only in the isolates with an intact ETT2. Moreover, ETT2 was more widely distributed in APEC isolates and exhibited more isoforms compared to ETT2 in human extraintestinal pathogenic E. coli, suggesting that APEC might be a potential risk to human health. However, there was no distinct correlation between ETT2 and other virulence factors in APEC.

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A highly conserved complete accessoryEscherichia colitype III secretion system 2 is widespread in bloodstream isolates of the ST69 lineage

10.1101/396804 ◽

2018 ◽

Author(s):

S. Fox ◽

C. Goswami ◽

M. Holden ◽

J.P.R. Connolly ◽

A. Roe ◽

...

Keyword(s):

Escherichia Coli ◽

Type Iii Secretion ◽

Type Iii Secretion System ◽

Secretion System ◽

Secretion Systems ◽

Functional Importance ◽

Effective Prevention ◽

E Coli ◽

Type Iii ◽

System 2

AbstractBacterial type III secretion systems (T3SS) play an important role in pathogenesis of Gram-negative infections. Enteropathogenic and enterohemorrhagicEscherichia colicontain a well-defined T3SS but in addition a second T3SS termedE. coliT3SS 2 (ETT2) has been described in a number of strains ofE. coli.The majority ofE. colicontain elements of a genetic locus encoding ETT2, but which has undergone significant mutational attrition rendering it without predicted function. Only a very few strains have been reported to contain an intact ETT2 locus. To investigate the occurrence of the ETT2 locus in strains of human pathogenicE. coli, we carried out genomic sequencing of 162 isolates obtained from patient blood cultures in Scotland. We found that all 26 ST69 isolates from this collection contained an intact ETT2 together with an associatedeiplocus which encodes putative secreted ETT2 effectors as well aseilA, a gene encoding a putative transcriptional regulator of ETT2 associated genes. Using a reporter gene foreilAactivation, we defined conditions under which this gene was differentially activated. However, comparison of secreted proteins from ST69 strains under high and loweilAactivation failed to identify any ETT2 secreted substrates. The conservation of the genes encoding ETT2 in human pathogenic ST69 strains strongly suggests it has functional importance in infection, although its exact functional role remains obscure.ImportanceOne of the commonest bacteria causing bloodstream infections in humans isEscherichia coli, which has a significant morbidity and mortality. Better understating of the mechanisms by which this microbe can invade blood could lead to more effective prevention and treatment. One mechanism by which some strains cause disease is by elaboration of a specialized secretion system, the type III secretion system (T3SS), encoded by the locus of enterocyte effacement (LEE). In addition to this well-defined T3SS, a second T3SS has been found in someE. colistrains termedE. colitype III secretion system 2 (ETT2). Most strains carry elements of the ETT2 locus, but with significant mutational attrition rendering it functionless. The significance of our work is that we have discovered that human bloodstream isolates ofE. coliof sequence type 69 contain a fully intact ETT2 and associated genes, strongly suggesting its functional importance in human infection.

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Regulators Encoded in the Escherichia coli Type III Secretion System 2 Gene Cluster Influence Expression of Genes within the Locus for Enterocyte Effacement in Enterohemorrhagic E. coli O157:H7

Infection and Immunity ◽

10.1128/iai.72.12.7282-7293.2004 ◽

2004 ◽

Vol 72 (12) ◽

pp. 7282-7293 ◽

Cited By ~ 68

Author(s):

Lihong Zhang ◽

Roy R. Chaudhuri ◽

Chrystala Constantinidou ◽

Jon L. Hobman ◽

Mala D. Patel ◽

...

Keyword(s):

Escherichia Coli ◽

Gene Cluster ◽

Type Iii Secretion ◽

Type Iii Secretion System ◽

Secretion System ◽

Regulatory Genes ◽

E Coli ◽

Type Iii ◽

System 2 ◽

Enterocyte Effacement

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) O157:H7 subverts host cells through a type III secretion system encoded by the locus for enterocyte effacement (LEE). Genome sequencing of this pathotype revealed the existence of a gene cluster encoding components of a second cryptic type III secretion system, E. coli type III secretion system 2 (ETT2). Recently, we showed that the ETT2 gene cluster is present in whole or in part in the majority of E. coli strains but is unable to encode a functional secretion system in most strains, including EHEC O157:H7. However, here we show that mutational inhibition of two regulatory genes (ECs3720 or etrA and ECs3734 or eivF) from the ETT2 cluster in EHEC O157:H7 leads to greatly increased secretion of proteins encoded by the LEE and to increased adhesion to human intestinal cells. Studies in which transcriptional fusions and microarrays were used indicated that EtrA and EivF exert profound negative effects on gene transcription within the LEE. Consistent with these observations, expression of these regulators in an EHEC O26:H- strain led to suppression of protein secretion under LEE-inducing conditions. These findings provide fresh examples of the influence of mobile genetic elements on regulation of the LEE and of cross talk between type III secretion system gene clusters. In addition, they provide a cautionary tale because they show that the effects of regulatory genes can outlive widespread decay of other genes in a functionally coherent gene cluster, a phenomenon that we have named the “Cheshire cat effect.” It also seems likely that variations in the ETT2 regulator repertoire might account for strain-to-strain variation in secretion of LEE-encoded proteins.

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DctR contributes to the virulence of avian pathogenic Escherichia coli through regulation of type III secretion system 2 expression

Veterinary Research ◽

10.1186/s13567-021-00970-6 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Yaodong Zhang ◽

Yao Wang ◽

Hong Zhu ◽

Zhengfei Yi ◽

Dossêh Jean Apôtre Afayibo ◽

...

Keyword(s):

Escherichia Coli ◽

Mutant Strain ◽

Type Iii Secretion ◽

Type Iii Secretion System ◽

Secretion System ◽

Economic Losses ◽

Type Iii ◽

Pathogenic Escherichia Coli ◽

Successful Infection ◽

System 2

AbstractPathogens could precisely alter their gene expression to facilitate their survival and successful infection. The LuxR family transcriptional regulator DctR (also known as YhiF) was shown to participate in the regulation of acid fitness and adhesion of enterohemorrhagic E. coli (EHEC) O157:H7. Avian pathogenic Escherichia coli (APEC) causes significant economic losses to the poultry industries and also potentially threatens human health. However, the effects of DctR on the fitness and virulence of APEC have not been investigated yet. To assess the function of DctR in APEC, the dctR gene mutant and complemented strains were constructed and biologically characterized. Our results show that inactivation of the dctR gene led to decreased biofilm formation, diminished serum resistance, reduced adherence capacity, attenuated colonization and virulence of APEC in ducks. The altered capacities of the mutant strain were restored by genetic complementation. In addition, we found that DctR positively regulates the expression of E. coli type III secretion system 2 (ETT2) core genes in APEC. The expression of the inflammatory cytokines interleukin (IL)-1β and IL-8 were decreased in HD-11 macrophages infected with the mutant strain compared with the wild-type strain. These observations indicate that regulator DctR contributes to the virulence of APEC through regulation of ETT2 expression.

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A Degenerate Type III Secretion System from Septicemic Escherichia coli Contributes to Pathogenesis

Journal of Bacteriology ◽

10.1128/jb.187.23.8164-8171.2005 ◽

2005 ◽

Vol 187 (23) ◽

pp. 8164-8171 ◽

Cited By ~ 44

Author(s):

Diana Ideses ◽

Uri Gophna ◽

Yossi Paitan ◽

Roy R. Chaudhuri ◽

Mark J. Pallen ◽

...

Keyword(s):

Escherichia Coli ◽

Gene Cluster ◽

Type Iii Secretion ◽

Type Iii Secretion System ◽

Gene Clusters ◽

Secretion System ◽

Effector Proteins ◽

E Coli ◽

Type Iii

ABSTRACT The type III secretion system (T3SS) is an important virulence factor used by several gram-negative bacteria to deliver effector proteins which subvert host cellular processes. Enterohemorrhagic Escherichia coli O157 has a well-defined T3SS involved in attachment and effacement (ETT1) and critical for virulence. A gene cluster potentially encoding an additional T3SS (ETT2), which resembles the SPI-1 system in Salmonella enterica, was found in its genome sequence. The ETT2 gene cluster has since been found in many E. coli strains, but its in vivo role is not known. Many of the ETT2 gene clusters carry mutations and deletions, raising the possibility that they are not functional. Here we show the existence in septicemic E. coli strains of an ETT2 gene cluster, ETT2sepsis, which, although degenerate, contributes to pathogenesis. ETT2sepsis has several premature stop codons and a large (5 kb) deletion, which is conserved in 11 E. coli strains from cases of septicemia and newborn meningitis. A null mutant constructed to remove genes coding for the putative inner membrane ring of the secretion complex exhibited significantly reduced virulence. These results are the first demonstration of the importance of ETT2 for pathogenesis.

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The role of Escherichia coli type III secretion system 2 chaperone protein ygeG in pathogenesis of avian pathogenic Escherichia coli

Research in Veterinary Science ◽

10.1016/j.rvsc.2021.09.011 ◽

2021 ◽

Vol 140 ◽

pp. 203-211

Author(s):

Lei Yin ◽

Qianwen Li ◽

Zeping Wang ◽

Jian Tu ◽

Ying Shao ◽

...

Keyword(s):

Escherichia Coli ◽

Type Iii Secretion ◽

Type Iii Secretion System ◽

Secretion System ◽

Avian Pathogenic Escherichia Coli ◽

Type Iii ◽

Chaperone Protein ◽

Pathogenic Escherichia Coli ◽

System 2

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The ETT2 Gene Cluster, Encoding a Second Type III Secretion System from Escherichia coli, Is Present in the Majority of Strains but Has Undergone Widespread Mutational Attrition

Journal of Bacteriology ◽

10.1128/jb.186.11.3547-3560.2004 ◽

2004 ◽

Vol 186 (11) ◽

pp. 3547-3560 ◽

Cited By ~ 73

Author(s):

Chuan-Peng Ren ◽

Roy R. Chaudhuri ◽

Amanda Fivian ◽

Christopher M. Bailey ◽

Martin Antonio ◽

...

Keyword(s):

Escherichia Coli ◽

Gene Cluster ◽

Type Iii Secretion ◽

Type Iii Secretion System ◽

Secretion System ◽

Genome Sequences ◽

Phylogenetic Structure ◽

E Coli ◽

Type Iii ◽

K 12

ABSTRACT ETT2 is a second cryptic type III secretion system in Escherichia coli which was first discovered through the analysis of genome sequences of enterohemorrhagic E. coli O157:H7. Comparative analyses of Escherichia and Shigella genome sequences revealed that the ETT2 gene cluster is larger than was previously thought, encompassing homologues of genes from the Spi-1, Spi-2, and Spi-3 Salmonella pathogenicity islands. ETT2-associated genes, including regulators and chaperones, were found at the same chromosomal location in the majority of genome-sequenced strains, including the laboratory strain K-12. Using a PCR-based approach, we constructed a complete tiling path through the ETT2 gene cluster for 79 strains, including the well-characterized E. coli reference collection supplemented with additional pathotypes. The ETT2 gene cluster was found to be present in whole or in part in the majority of E. coli strains, whether pathogenic or commensal, with patterns of distribution and deletion mirroring the known phylogenetic structure of the species. In almost all strains, including enterohemorrhagic E. coli O157:H7, ETT2 has been subjected to varying degrees of mutational attrition that render it unable to encode a functioning secretion system. A second type III secretion system-associated locus that likely encodes the ETT2 translocation apparatus was found in some E. coli strains. Intact versions of both ETT2-related clusters are apparently present in enteroaggregative E. coli strain O42.

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