scholarly journals Control freaks—signals and cues governing the regulation of virulence in attaching and effacing pathogens

2018 ◽  
Vol 47 (1) ◽  
pp. 229-238 ◽  
Author(s):  
Natasha C.A. Turner ◽  
James P.R. Connolly ◽  
Andrew J. Roe

AbstractEnterohaemorrhagic Escherichia coli (EHEC) mediates disease using a type 3 secretion system (T3SS), which is encoded on the locus of enterocyte effacement (LEE) and is tightly controlled by master regulators. This system is further modulated by a number of signals that help to fine-tune virulence, including metabolic, environmental and chemical signals. Since the LEE and its master regulator, Ler, were established, there have been numerous scientific advancements in understanding the regulation and expression of virulence factors in EHEC. This review will discuss the recent advancements in this field since our previous review, with a focus on the transcriptional regulation of the LEE.

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Sagi Huja ◽  
Yaara Oren ◽  
Eva Trost ◽  
Elzbieta Brzuszkiewicz ◽  
Dvora Biran ◽  
...  

ABSTRACTHere we present an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78 that represent the major cause of avian colisepticemia, an invasive infection caused by avian pathogenicEscherichia coli(APEC) strains. It is associated with high mortality and morbidity, resulting in significant economic consequences for the poultry industry. To understand the genetic basis of the virulence of avian septicemic E. coli, we sequenced the entire genome of a clinical isolate of serotype O78—O78:H19 ST88 isolate 789 (O78-9)—and compared it with three publicly available APEC O78 sequences and one complete genome of APEC serotype O1 strain. Although there was a large variability in genome content between the APEC strains, several genes were conserved, which are potentially critical for colisepticemia. Some of these genes are present in multiple copies per genome or code for gene products with overlapping function, signifying their importance. A systematic deletion of each of these virulence-related genes identified three systems that are conserved in all septicemic strains examined and are critical for serum survival, a prerequisite for septicemia. These are the plasmid-encoded protein, the defective ETT2 (E. colitype 3 secretion system 2) type 3 secretion system ETT2sepsis, and iron uptake systems. Strain O78-9 is the only APEC O78 strain that also carried the regulon coding for yersiniabactin, the iron binding system of theYersiniahigh-pathogenicity island. Interestingly, this system is the only one that cannot be complemented by other iron uptake systems under iron limitation and in serum.IMPORTANCEAvian colisepticemia is a severe systemic disease of birds causing high morbidity and mortality and resulting in severe economic losses. The bacteria associated with avian colisepticemia are highly antibiotic resistant, making antibiotic treatment ineffective, and there is no effective vaccine due to the multitude of serotypes involved. To understand the disease and work out strategies to combat it, we performed an extensive genomic and genetic analysis of Escherichia coli strains of serotype O78, the major cause of the disease. We identified several potential virulence factors, conserved in all the colisepticemic strains examined, and determined their contribution to growth in serum, an absolute requirement for septicemia. These findings raise the possibility that specific vaccines or drugs can be developed against these critical virulence factors to help combat this economically important disease.


mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Farid Tejeda-Dominguez ◽  
Jazmin Huerta-Cantillo ◽  
Lucia Chavez-Dueñas ◽  
Fernando Navarro-Garcia

ABSTRACT The type 3 secretion system (T3SS) is essential for bacterial virulence through delivering effector proteins directly into the host cytosol. Here, we identified an alternative delivery mechanism of virulence factors mediated by the T3SS, which consists of the association of extracellularly secreted proteins from bacteria with the T3SS to gain access to the host cytosol. Both EspC, a protein secreted as an enteropathogenic Escherichia coli (EPEC) autotransporter, and YopH, a protein detected on the surface of Yersinia, require a functional T3SS for host cell internalization; here we provide biophysical and molecular evidence to support the concept of the EspC translocation mechanism, which requires (i) an interaction between EspA and an EspC middle segment, (ii) an EspC translocation motif (21 residues that are shared with the YopH translocation motif), (iii) increases in the association and dissociation rates of EspC mediated by EspA interacting with EspD, and (iv) an interaction of EspC with the EspD/EspB translocon pore. Interestingly, this novel mechanism does not exclude the injection model (i.e., EspF) operating through the T3SS conduit; therefore, T3SS can be functioning as an internal conduit or as an external railway, which can be used to reach the translocator pore, and this mechanism appears to be conserved among different T3SS-dependent pathogens. IMPORTANCE The type 3 secretion system is essential for injection of virulence factors, which are delivered directly into the cytosol of the host cells for usurping and subverting host processes. Recent studies have shown that these effectors proteins indeed travel inside an “injectisome” conduit through a single step of translocation by connecting the bacterium and host cell cytoplasms. However, all findings are not compatible with this model. For example, both YopH, a protein detected on the surface of Yersinia, and EspC, an autotransporter protein secreted by enteropathogenic E. coli, require a functional T3SS for host cell translocation. Both proteins have an intermediate extracellular step before their T3SS-dependent translocation. Here, we show an alternative delivery mechanism for these extracellularly secreted virulence factors that are then incorporated into the T3SS to enter the cells; this novel mechanism coexists with but diverges from the canonical injection model that involves the passage of the protein inside the injectisome. The type 3 secretion system is essential for injection of virulence factors, which are delivered directly into the cytosol of the host cells for usurping and subverting host processes. Recent studies have shown that these effectors proteins indeed travel inside an “injectisome” conduit through a single step of translocation by connecting the bacterium and host cell cytoplasms. However, all findings are not compatible with this model. For example, both YopH, a protein detected on the surface of Yersinia, and EspC, an autotransporter protein secreted by enteropathogenic E. coli, require a functional T3SS for host cell translocation. Both proteins have an intermediate extracellular step before their T3SS-dependent translocation. Here, we show an alternative delivery mechanism for these extracellularly secreted virulence factors that are then incorporated into the T3SS to enter the cells; this novel mechanism coexists with but diverges from the canonical injection model that involves the passage of the protein inside the injectisome.


2014 ◽  
Vol 45 (3) ◽  
pp. 851-855 ◽  
Author(s):  
Fábia A. Salvador ◽  
Rodrigo T. Hernandes ◽  
Mônica A.M. Vieira ◽  
Anna C. Rockstroh ◽  
Tânia A.T. Gomes

2014 ◽  
Vol 9 (4) ◽  
pp. 1039-1051 ◽  
Author(s):  
James PR Connolly ◽  
Robert J Goldstone ◽  
Karl Burgess ◽  
Richard J Cogdell ◽  
Scott A Beatson ◽  
...  

Abstract Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity.


Microbiology ◽  
2009 ◽  
Vol 155 (2) ◽  
pp. 541-550 ◽  
Author(s):  
Hidetada Hirakawa ◽  
Toshio Kodama ◽  
Asuka Takumi-Kobayashi ◽  
Takeshi Honda ◽  
Akihito Yamaguchi

Indole is produced by tryptophanase during growth of enteric bacteria and accumulates in the culture medium. The physiological role of indole production is poorly understood. We discovered that enterohaemorrhagic Escherichia coli (EHEC) O157 : H7 with a tnaA deletion has decreased secretion of EspA and EspB via the type III secretion system and as a result there is reduced formation of attaching and effacing (A/E) lesions in HeLa cells. Addition of indole restored and enhanced secretion of EspA and EspB and formation of A/E lesions by the tnaA deletion mutant EHEC. Indole addition moderately increased the promoter activity of LEE4 genes, including espA and espB, in the locus of enterocyte effacement. Thus in EHEC indole can serve to signal EspA and EspB expression and secretion and stimulate the ability of EHEC to form A/E lesions on human cells.


2021 ◽  
Vol 9 (1) ◽  
pp. 187
Author(s):  
Doron Teper ◽  
Sheo Shankar Pandey ◽  
Nian Wang

Bacteria of the genus Xanthomonas cause a wide variety of economically important diseases in most crops. The virulence of the majority of Xanthomonas spp. is dependent on secretion and translocation of effectors by the type 3 secretion system (T3SS) that is controlled by two master transcriptional regulators HrpG and HrpX. Since their discovery in the 1990s, the two regulators were the focal point of many studies aiming to decipher the regulatory network that controls pathogenicity in Xanthomonas bacteria. HrpG controls the expression of HrpX, which subsequently controls the expression of T3SS apparatus genes and effectors. The HrpG/HrpX regulon is activated in planta and subjected to tight metabolic and genetic regulation. In this review, we cover the advances made in understanding the regulatory networks that control and are controlled by the HrpG/HrpX regulon and their conservation between different Xanthomonas spp.


2009 ◽  
Vol 72 (7) ◽  
pp. 1531-1537 ◽  
Author(s):  
JUAN XICOHTENCATL-CORTES ◽  
ETHEL SÁNCHEZ CHACÓN ◽  
ZEUS SALDAÑA ◽  
ENRIQUE FREER ◽  
JORGE A. GIRÓN

Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen responsible for human diarrheal disease. EHEC lives in the intestinal tract of cattle and other farm and wild animals, which may be the source of environmental contamination particularly of agricultural fields. Human infections are associated with consumption of tainted animal products and fresh produce. How the bacteria interact with the plant phyllosphere and withstand industrial decontamination remain to be elucidated. The goals of the present study were to investigate the environmental conditions and surface structures that influence the interaction of EHEC O157:H7 with baby spinach and lettuce leaves in vitro. Independently of the production of Shiga toxin, EHEC O157:H7 colonizes the leaf surface via flagella and the type 3 secretion system (T3SS). Ultrastructural analysis of EHEC-infected leafy greens revealed the presence of flagellated bacteria, and mutation of the fliC flagellin gene in EHEC EDL933 rendered the bacteria significantly less adherent, suggesting the involvement of flagella in the bacteria-leaf interaction. EDL933 mutated in the escN (ATPase) gene associated with the function of the T3SS but not in the eae (intimin adhesin) gene required for adherence to host intestinal cells had significantly reduced adherence compared with that of the parental strain. The data suggest a compelling role of flagella and the T3SS in colonization of leafy green produce. Colonization of salad leaves by EHEC strains may be a strategy that ensures survival of these bacteria in the environment and allows transmission to the human host.


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