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

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Yaodong Zhang ◽  
Yao Wang ◽  
Hong Zhu ◽  
Zhengfei Yi ◽  
Dossêh Jean Apôtre Afayibo ◽  
...  

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.

2016 ◽  
Vol 144 (13) ◽  
pp. 2824-2830 ◽  
Author(s):  
S. WANG ◽  
X. LIU ◽  
X. XU ◽  
Y. ZHAO ◽  
D. YANG ◽  
...  

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.


2018 ◽  
Author(s):  
S. Fox ◽  
C. Goswami ◽  
M. Holden ◽  
J.P.R. Connolly ◽  
A. Roe ◽  
...  

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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Stephen Fox ◽  
Cosmika Goswami ◽  
Matthew Holden ◽  
James P. R. Connolly ◽  
James Mordue ◽  
...  

2004 ◽  
Vol 72 (12) ◽  
pp. 7282-7293 ◽  
Author(s):  
Lihong Zhang ◽  
Roy R. Chaudhuri ◽  
Chrystala Constantinidou ◽  
Jon L. Hobman ◽  
Mala D. Patel ◽  
...  

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.


2014 ◽  
Vol 45 (1) ◽  
pp. 32 ◽  
Author(s):  
Mingxu Zhou ◽  
Zhiyan Guo ◽  
Qiangde Duan ◽  
Philip R Hardwidge ◽  
Guoqiang Zhu

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