scholarly journals Salmonella Pathogenicity Island 1 (SPI-1): The Evolution and Stabilization of a Core Genomic Type Three Secretion System

2020 ◽  
Vol 8 (4) ◽  
pp. 576
Author(s):  
Nicole A. Lerminiaux ◽  
Keith D. MacKenzie ◽  
Andrew D. S. Cameron
Keyword(s):  
Transcription Factors ◽  
Pathogenicity Island ◽  
Secretion System ◽  
Effector Proteins ◽  
Gene Promoters ◽  
Salmonella Pathogenicity Island ◽  
Evolutionary Origins ◽  
Type Three Secretion System ◽  
History Of ◽  
Type Three Secretion

Salmonella Pathogenicity Island 1 (SPI-1) encodes a type three secretion system (T3SS), effector proteins, and associated transcription factors that together enable invasion of epithelial cells in animal intestines. The horizontal acquisition of SPI-1 by the common ancestor of all Salmonella is considered a prime example of how gene islands potentiate the emergence of new pathogens with expanded niche ranges. However, the evolutionary history of SPI-1 has attracted little attention. Here, we apply phylogenetic comparisons across the family Enterobacteriaceae to examine the history of SPI-1, improving the resolution of its boundaries and unique architecture by identifying its composite gene modules. SPI-1 is located between the core genes fhlA and mutS, a hotspot for the gain and loss of horizontally acquired genes. Despite the plasticity of this locus, SPI-1 demonstrates stable residency of many tens of millions of years in a host genome, unlike short-lived homologous T3SS and effector islands including Escherichia ETT2, Yersinia YSA, Pantoea PSI-2, Sodalis SSR2, and Chromobacterium CPI-1. SPI-1 employs a unique series of regulatory switches, starting with the dedicated transcription factors HilC and HilD, and flowing through the central SPI-1 regulator HilA. HilA is shared with other T3SS, but HilC and HilD may have their evolutionary origins in Salmonella. The hilA, hilC, and hilD gene promoters are the most AT-rich DNA in SPI-1, placing them under tight control by the transcriptional repressor H-NS. In all Salmonella lineages, these three promoters resist amelioration towards the genomic average, ensuring strong repression by H-NS. Hence, early development of a robust and well-integrated regulatory network may explain the evolutionary stability of SPI-1 compared to T3SS gene islands in other species.

scholarly journals Regulation of the Locus of Enterocyte Effacement in Attaching and Effacing Pathogens

2017 ◽  
Vol 200 (2) ◽  
Author(s):  
R. Christopher D. Furniss ◽  
Abigail Clements
Keyword(s):  
Secretion System ◽  
Effector Proteins ◽  
The Core ◽  
Genetic Feature ◽  
Gut Epithelium ◽  
Type Three Secretion System ◽  
Gut Mucosa ◽  
Enterocyte Effacement ◽  
Type Three Secretion ◽  
Complex Regulatory Network

ABSTRACTAttaching and effacing (AE) pathogens colonize the gut mucosa using a type three secretion system (T3SS) and a suite of effector proteins. The locus of enterocyte effacement (LEE) is the defining genetic feature of the AE pathogens, encoding the T3SS and the core effector proteins necessary for pathogenesis. Extensive research has revealed a complex regulatory network that senses and responds to a myriad of host- and microbiota-derived signals in the infected gut to control transcription of the LEE. These signals include microbiota-liberated sugars and metabolites in the gut lumen, molecular oxygen at the gut epithelium, and host hormones. Recent research has revealed that AE pathogens also recognize physical signals, such as attachment to the epithelium, and that the act of effector translocation remodels gene expression in infecting bacteria. In this review, we summarize our knowledge to date and present an integrated view of how chemical, geographical, and physical cues regulate the virulence program of AE pathogens during infection.

scholarly journals Chemical Inhibitors of the Type Three Secretion System: Disarming Bacterial Pathogens

2012 ◽  
Vol 56 (11) ◽  
pp. 5433-5441 ◽  
Author(s):  
Miles C. Duncan ◽  
Roger G. Linington ◽  
Victoria Auerbuch
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogens ◽  
Secretion System ◽  
Effector Proteins ◽  
Host Cells ◽  
Magic Bullet ◽  
Antimicrobial Drugs ◽  
Type Three Secretion System ◽  
Type Three Secretion

ABSTRACTThe recent and dramatic rise of antibiotic resistance among bacterial pathogens underlies the fear that standard treatments for infectious disease will soon be largely ineffective. Resistance has evolved against nearly every clinically used antibiotic, and in the near future, we may be hard-pressed to treat bacterial infections previously conquered by “magic bullet” drugs. While traditional antibiotics kill or slow bacterial growth, an important emerging strategy to combat pathogens seeks to block the ability of bacteria to harm the host by inhibiting bacterial virulence factors. One such virulence factor, the type three secretion system (T3SS), is found in over two dozen Gram-negative pathogens and functions by injecting effector proteins directly into the cytosol of host cells. Without T3SSs, many pathogenic bacteria are unable to cause disease, making the T3SS an attractive target for novel antimicrobial drugs. Interdisciplinary efforts between chemists and microbiologists have yielded several T3SS inhibitors, including the relatively well-studied salicylidene acylhydrazides. This review highlights the discovery and characterization of T3SS inhibitors in the primary literature over the past 10 years and discusses the future of these drugs as both research tools and a new class of therapeutic agents.

scholarly journals Characterisation of Yersinia secretion apparatus-pathogenicity island (Ysa-PI) of Yersinia enterocolitica 1B/O8 in Poland: an idle Ysa is a specific hallmark of the epidemic sensu stricto strain

2015 ◽  
Vol 64 (2) ◽  
pp. 171-174
Author(s):  
TOMASZ WOŁKOWICZ ◽  
KATARZYNA ZACHARCZUK ◽  
NATALIA ROKOSZ-CHUDZIAK ◽  
WALDEMAR RASTAWICKI ◽  
RAFAŁ GIERCZYŃSKI
Keyword(s):  
Stop Codon ◽  
Regulatory Gene ◽  
Premature Stop Codon ◽  
Pathogenicity Island ◽  
Sensu Stricto ◽  
Secretion System ◽  
Clinical Samples ◽  
Type Three Secretion System ◽  
Type Three Secretion ◽  
Chromosomal Type

Yersinia secretion apparatus (Ysa), the chromosomal type three secretion system (T3SS) is considered to contribute to virulence of high-pathogenicity Yersina enterocolitica biovar 1B. DNA-sequence of Ysa pathogenicity island was determined for clinical isolate DM0110 of Y enterocolitica 1B/08 with origin in Poland. We found a premature stop-codon in the regulatory gene ysrR (mutation at position 269). Altered ysrR was detected in all tested 78 isolates of Y enterocolitica 1B/O8 collected from clinical samples in Poland from 2004 to 2013. Since aberrations in YsrR are considered to inactivate Ysa, our findings may suggest Ysa is not indispensable for Y enterocolitica 1B/O8 to infect humans.

scholarly journals Arginine glycosylation enhances methylglyoxal detoxification

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samir El Qaidi ◽  
Nichollas E. Scott ◽  
Philip R. Hardwidge
Keyword(s):  
Secretion System ◽  
Effector Proteins ◽  
Glutathione Synthetase ◽  
Synthetase Activity ◽  
Host Cell Proteins ◽  
T3ss Effector ◽  
Type Three Secretion System ◽  
Arginine Residues ◽  
Host Signaling ◽  
Type Three Secretion

AbstractType III secretion system effector proteins have primarily been characterized for their interactions with host cell proteins and their ability to disrupt host signaling pathways. We are testing the hypothesis that some effectors are active within the bacterium, where they modulate bacterial signal transduction and physiology. We previously determined that the Citrobacter rodentium effector NleB possesses an intra-bacterial glycosyltransferase activity that increases glutathione synthetase activity to protect the bacterium from oxidative stress. Here we investigated the potential intra-bacterial activities of NleB orthologs in Salmonella enterica and found that SseK1 and SseK3 mediate resistance to methylglyoxal. SseK1 glycosylates specific arginine residues on four proteins involved in methylglyoxal detoxification, namely GloA (R9), GloB (R190), GloC (R160), and YajL (R149). SseK1-mediated Arg-glycosylation of these four proteins significantly enhances their catalytic activity, thus providing another important example of the intra-bacterial activities of type three secretion system effector proteins. These data are also the first demonstration that a Salmonella T3SS effector is active within the bacterium.

scholarly journals SpiC Is Required for Translocation of Salmonella Pathogenicity Island 2 Effectors and Secretion of Translocon Proteins SseB and SseC

2002 ◽  
Vol 184 (18) ◽  
pp. 4971-4980 ◽  
Author(s):  
Jeremy A. Freeman ◽  
Catherine Rappl ◽  
Volker Kuhle ◽  
Michael Hensel ◽  
Samuel I. Miller
Keyword(s):  
Type Iii Secretion ◽  
Pathogenicity Island ◽  
Secretion System ◽  
Effector Proteins ◽  
Mutant Phenotype ◽  
Eukaryotic Cells ◽  
Large Contribution ◽  
Salmonella Pathogenicity Island ◽  
Virulence Phenotype ◽  
Serovar Typhimurium

ABSTRACT The Salmonella pathogenicity island 2 (SPI2) type III secretion system (TTSS) promotes Salmonella enterica serovar Typhimurium virulence for mice and increased survival and replication within eukaryotic cells. After phagocytosis, Salmonella serovar Typhimurium assembles the SPI2 TTSS to translocate over a dozen effector proteins across the phagosome membrane. SpiC has been previously shown to be a translocated effector with a large contribution to virulence (K. Uchiya, M. A. Barbieri, K. Funato, A. H. Shah, P. D. Stahl, and E. A. Groisman, EMBO J. 18:3924-3933, 1999). This report demonstrates by competitive index that the virulence phenotype of a spiC mutant is equivalent to that of a secretion component mutant. In addition, translocation of SPI2 effector proteins was shown to require SpiC. Thus, the severe virulence phenotype resulting from deletion of spiC is likely due to the inability to translocate all SPI2 effectors. SpiC was also required to secrete translocon proteins SseB and SseC but not translocated effector SseJ, indicating that lack of assembly of the translocon explains the spiC mutant phenotype.

scholarly journals HilD, HilC, and RtsA Form Homodimers and Heterodimers To Regulate Expression of the Salmonella Pathogenicity Island I Type III Secretion System

2020 ◽  
Vol 202 (9) ◽  
Author(s):  
Koh-Eun Narm ◽  
Marinos Kalafatis ◽  
James M. Slauch
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Systemic Disease ◽  
Pathogenicity Island ◽  
Secretion System ◽  
Dimerization Domain ◽  
Content Type ◽  
Network Function ◽  
Type Three Secretion System ◽  
Type Three Secretion

ABSTRACT Salmonella enterica serovar Typhimurium colonizes and invades host intestinal epithelial cells using the type three secretion system (T3SS) encoded on Salmonella pathogenicity island 1 (SPI1). The level of SPI1 T3SS gene expression is controlled by the transcriptional activator HilA, encoded on SPI1. Expression of hilA is positively regulated by three homologous transcriptional regulators, HilD, HilC, and RtsA, belonging to the AraC/XylS family. These regulators also activate the hilD, hilC, and rtsA genes by binding to the same DNA sequences upstream of these promoters, forming a complex feed-forward loop to control SPI1 expression. Despite the apparent redundancy in function, HilD has a unique role in SPI1 regulation because the majority of external regulatory inputs act exclusively through HilD. To better understand SPI1 regulation, the nature of interaction between HilD, HilC, and RtsA has been characterized using biochemical and genetic techniques. Our results showed that HilD, HilC, and RtsA can form heterodimers as well as homodimers in solution. Comparison with other AraC family members identified a putative α-helix in the N-terminal domain, which acts as the dimerization domain. Alanine substitution in this region results in reduced dimerization of HilD and HilC and also affects their ability to activate hilA expression. The dimer interactions of HilD, HilC, and RtsA add another layer of complexity to the SPI1 regulatory circuit, providing a more comprehensive understanding of SPI1 T3SS regulation and Salmonella pathogenesis. IMPORTANCE The SPI1 type three secretion system is a key virulence factor required for Salmonella to both cause gastroenteritis and initiate serious systemic disease. The system responds to numerous environmental signals in the intestine, integrating this information via a complex regulatory network. Here, we show that the primary regulatory proteins in the network function as both homodimers and heterodimers, providing information regarding both regulation of virulence in this important pathogen and general signal integration to control gene expression.

An inhibitory mechanism of action of coiled‐coil peptides against type three secretion system from enteropathogenicEscherichia coli

2019 ◽  
Vol 25 (3) ◽  
Author(s):  
Mariano Larzábal ◽  
Hector A. Baldoni ◽  
Fernando D. Suvire ◽  
Lucrecia M. Curto ◽  
Gabriela E. Gomez ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Coiled Coil ◽  
Secretion System ◽  
Inhibitory Mechanism ◽  
Type Three Secretion System ◽  
Type Three Secretion
Sign in / Sign up

Export Citation Format

Share Document