scholarly journals FliZ Regulates Expression of the Salmonella Pathogenicity Island 1 Invasion Locus by Controlling HilD Protein Activity in Salmonella enterica Serovar Typhimurium

2010 ◽  
Vol 192 (23) ◽  
pp. 6261-6270 ◽  
Author(s):  
Jessica E. Cott Chubiz ◽  
Yekaterina A. Golubeva ◽  
Dongxia Lin ◽  
Lucas D. Miller ◽  
James M. Slauch
Keyword(s):  
Salmonella Enterica ◽  
Direct Injection ◽  
Systemic Disease ◽  
Systemic Infection ◽  
Pathogenicity Island ◽  
Effector Proteins ◽  
Negative Regulator ◽  
Bacterial Invasion ◽  
Protein Activity ◽  
Environmental Signals

ABSTRACT A prerequisite for Salmonella enterica to cause both intestinal and systemic disease is the direct injection of effector proteins into host intestinal epithelial cells via a type three secretion system (T3SS); the T3SS genes are carried on Salmonella pathogenicity island 1 (SPI1). These effector proteins induce inflammatory diarrhea and bacterial invasion. Expression of the SPI1 T3SS is tightly regulated in response to environmental signals through a variety of global regulatory systems. We have previously shown that three AraC-like regulators, HilD, HilC, and RtsA, act in a complex feed-forward regulatory loop to control the expression of the hilA gene, which encodes the direct regulator of the SPI1 structural genes. In this work, we characterize a major positive regulator of this system, the flagellar protein FliZ. Through genetic and biochemical analyses, we show that FliZ posttranslationally controls HilD to positively regulate hilA expression. This mechanism is independent of other flagellar components and is not mediated through the negative regulator HilE or through FliZ-mediated RpoS regulation. We demonstrate that FliZ controls HilD protein activity and not stability. FliZ regulates HilD in the absence of Lon protease, previously shown to degrade HilD. Indeed, it appears that FliZ, rather than HilD, is the most relevant target of Lon as it relates to SPI1 expression. Mutants lacking FliZ are significantly attenuated in their ability to colonize the intestine but are unaffected during systemic infection. The intestinal attenuation is partially dependent on SPI1, but FliZ has additional pleiotropic effects.

scholarly journals The DnaK/DnaJ Chaperone Machinery of Salmonella enterica Serovar Typhimurium Is Essential for Invasion of Epithelial Cells and Survival within Macrophages, Leading to Systemic Infection

2004 ◽  
Vol 72 (3) ◽  
pp. 1364-1373 ◽  
Author(s):  
Akiko Takaya ◽  
Toshifumi Tomoyasu ◽  
Hidenori Matsui ◽  
Tomoko Yamamoto
Keyword(s):  
Epithelial Cells ◽  
Salmonella Enterica ◽  
Stress Proteins ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Disease ◽  
Systemic Infection ◽  
Bacterial Invasion ◽  
Temperature Sensitive ◽  
Serovar Typhimurium ◽  
First Time

ABSTRACT Salmonella enterica serovar Typhimurium, similar to various facultative intracellular pathogens, has been shown to respond to the hostile conditions inside macrophages of the host organism by inducing stress proteins, such as DnaK. DnaK forms a chaperone machinery with the cochaperones DnaJ and GrpE. To elucidate the role of the DnaK chaperone machinery in the pathogenesis of S. enterica serovar Typhimurium, we first constructed an insertional mutation in the dnaK-dnaJ operon of pathogenic strain χ3306. The DnaK/DnaJ-depleted mutant was temperature sensitive for growth, that is, nonviable above 39°C. We then isolated a spontaneously occurring revertant of the dnaK-dnaJ-disrupted mutant at 39°C and used it for infection of mice. The mutant lost the ability to cause a lethal systemic disease in mice. The impaired ability for virulence was restored when a functional copy of the dnaK-dnaJ operon was provided, suggesting that the DnaK/DnaJ chaperone machinery is required by Salmonella for the systemic infection of mice. This result also indicates that with respect to the DnaK/DnaJ chaperone machinery, the cellular requirements for growth at a high temperature are not identical to the cellular requirements for the pathogenesis of Salmonella. Macrophage survival assays revealed that the DnaK/DnaJ-depleted mutant could not survive or proliferate at all within macrophages. Of further interest are the findings that the mutant could neither invade cultured epithelial cells nor secrete any of the invasion proteins encoded within Salmonella pathogenicity island 1. This is the first time that the DnaK/DnaJ chaperone machinery has been shown to be involved in bacterial invasion of epithelial cells.

scholarly journals Caveolin-1-Deficient Mice Show Defects in Innate Immunity and Inflammatory Immune Response during Salmonella enterica Serovar Typhimurium Infection

2006 ◽  
Vol 74 (12) ◽  
pp. 6665-6674 ◽  
Author(s):  
Freddy A. Medina ◽  
Cecilia J. de Almeida ◽  
Elliott Dew ◽  
Jiangwei Li ◽  
Gloria Bonuccelli ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Salmonella Enterica ◽  
Inflammatory Responses ◽  
Systemic Infection ◽  
Bacterial Invasion ◽  
Chemokine Production ◽  
Caveolin 1 ◽  
Serovar Typhimurium ◽  
Deficient Mice

ABSTRACT A number of studies have shown an association of pathogens with caveolae. To this date, however, there are no studies showing a role for caveolin-1 in modulating immune responses against pathogens. Interestingly, expression of caveolin-1 has been shown to occur in a regulated manner in immune cells in response to lipopolysaccharide (LPS). Here, we sought to determine the role of caveolin-1 (Cav-1) expression in Salmonella pathogenesis. Cav-1−/− mice displayed a significant decrease in survival when challenged with Salmonella enterica serovar Typhimurium. Spleen and tissue burdens were significantly higher in Cav-1−/− mice. However, infection of Cav-1−/− macrophages with serovar Typhimurium did not result in differences in bacterial invasion. In addition, Cav-1−/− mice displayed increased production of inflammatory cytokines, chemokines, and nitric oxide. Regardless of this, Cav-1−/− mice were unable to control the systemic infection of Salmonella. The increased chemokine production in Cav-1−/− mice resulted in greater infiltration of neutrophils into granulomas but did not alter the number of granulomas present. This was accompanied by increased necrosis in the liver. However, Cav-1−/− macrophages displayed increased inflammatory responses and increased nitric oxide production in vitro in response to Salmonella LPS. These results show that caveolin-1 plays a key role in regulating anti-inflammatory responses in macrophages. Taken together, these data suggest that the increased production of toxic mediators from macrophages lacking caveolin-1 is likely to be responsible for the marked susceptibility of caveolin-1-deficient mice to S. enterica serovar Typhimurium.

scholarly journals The fimYZ Genes Regulate Salmonella enterica Serovar Typhimurium Invasion in Addition to Type 1 Fimbrial Expression and Bacterial Motility

2005 ◽  
Vol 73 (3) ◽  
pp. 1377-1385 ◽  
Author(s):  
M. Aaron Baxter ◽  
Bradley D. Jones
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Protein Interactions ◽  
Salmonella Enterica ◽  
Negative Regulator ◽  
Invasive Phenotype ◽  
Environmental Signals ◽  
Bacterial Physiology ◽  
Serovar Typhimurium

ABSTRACT An important step in Salmonella enterica serovar Typhimurium virulence is the ability to invade the intestinal epithelium. The invasion process requires a large number of genes encoded on Salmonella pathogenicity island 1 (SPI-1) at centisome 63 as well as genes located in other positions throughout the chromosome. Expression of the invasive phenotype is tightly regulated by environmental cues that are processed by a complex regulatory scheme. A central player in the invasion regulatory pathway is the HilA protein, which is transcriptional activator belonging to the OmpR/ToxR family. A number of positive regulators (hilC, hilD, fis, sirA/barA, csrAB, phoBR, fadD, envZ/ompR, and fliZ) and negative regulators (hha, hilE, lon, ams, phoP c and pag) have been identified that are able to alter expression of hilA transcription. Recent work has found that hilA transcription requires the HilD protein for activation. Other work has emphasized the importance of HilE as a negative regulator of hilA. Overexpression of hilE superrepresses hilA transcription, as well as the invasive phenotype. Two-hybrid experiments suggest that HilE exerts its regulatory influence on hilA through protein-protein interactions with HilD as the protein does not bind to the hilA promoter nor does it affect hilD transcription. As it seems likely that hilE plays an important role in translating environmental signals into invasion gene regulation, we have attempted to identify how the hilE gene itself is regulated. Our results indicate that the fimYZ genes, response regulatory proteins involved in type 1 fimbrial gene expression and recently implicated in motility gene regulation, are important activators of hilE expression. These findings indicate that invasion gene expression is coregulated with motility and adherence and provide experimental evidence that the expression of these virulence phenotypes is a subset of the overall regulation of bacterial physiology.

scholarly journals The Invasion Plasmid Antigen J (IpaJ) from Salmonella Inhibits NF-κB Activation by Suppressing IκBα Ubiquitination

2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Qiuchun Li ◽  
Lijuan Xu ◽  
Chao Yin ◽  
Zijian Liu ◽  
Yang Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Hela Cells ◽  
Salmonella Enterica ◽  
Systemic Infection ◽  
Peripheral Blood Monocyte ◽  
Effector Proteins ◽  
Economic Losses ◽  
Necrosis Factor Alpha ◽  
Content Type

ABSTRACT Salmonella enterica serovar Pullorum is the pathogen of pullorum disease, which leads to severe economic losses in many developing countries. In contrast to the strong inflammatory response induced by Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis, S. Pullorum causes systemic infection with little inflammation. The effector proteins secreted by Salmonella often play a crucial role in modulating host signal transduction and cellular processes to the pathogen’s advantage. In the present study, the invasion plasmid antigen J (IpaJ) protein specifically identified in S. Pullorum was found to significantly inhibit activation of the key proinflammatory transcription factor, NF-κB, which was induced by tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and lipopolysaccharide (LPS). IpaJ inhibited the NF-κB pathway in cells infected with S. Pullorum through the stabilization of IκBα. Deletion of ipaJ in S. Pullorum caused a significantly increased level of ubiquitinated IκBα that was subsequently degraded by the proteasome in HeLa cells. Moreover, IpaJ was efficient in the prevention of NF-κB translocation to the nucleus and ultimately interfered with the secretion of the proinflammatory cytokines IL-1β, IL-6, and IL-8 in infected HeLa cells. Additionally, the transformation of ipaJ into S. Enteritidis decreased the secretion of proinflammatory cytokines in HeLa cells through suppression of the NF-κB pathway. The infection of chicken peripheral blood monocyte-derived macrophages (chMDM) confirmed that ipaJ-deleted S. Pullorum induced a stronger expression of proinflammatory cytokines than the wild-type and complementary strains. In summary, the present study revealed that IpaJ functions as an important anti-inflammatory protein involved in S. Pullorum infection through inhibition of the NF-κB pathway and the subsequent inflammatory response.

scholarly journals QseC Mediates Salmonella enterica Serovar Typhimurium Virulence In Vitro and In Vivo

2009 ◽  
Vol 78 (3) ◽  
pp. 914-926 ◽  
Author(s):  
Cristiano G. Moreira ◽  
David Weinshenker ◽  
Vanessa Sperandio
Keyword(s):  
Epithelial Cells ◽  
Salmonella Enterica ◽  
Systemic Disease ◽  
Systemic Infection ◽  
Flagellar Motility ◽  
Signaling System ◽  
Interkingdom Signaling ◽  
Serovar Typhimurium

ABSTRACT The autoinducer-3 (AI-3)/epinephrine (Epi)/norepinephrine (NE) interkingdom signaling system mediates chemical communication between bacteria and their mammalian hosts. The three signals are sensed by the QseC histidine kinase (HK) sensor. Salmonella enterica serovar Typhimurium is a pathogen that uses HKs to sense its environment and regulate virulence. Salmonella serovar Typhimurium invades epithelial cells and survives within macrophages. Invasion of epithelial cells is mediated by the type III secretion system (T3SS) encoded in Salmonella pathogenicity island 1 (SPI-1), while macrophage survival and systemic disease are mediated by the T3SS encoded in SPI-2. Here we show that QseC plays an important role in Salmonella serovar Typhimurium pathogenicity. A qseC mutant was impaired in flagellar motility, in invasion of epithelial cells, and in survival within macrophages and was attenuated for systemic infection in 129x1/SvJ mice. QseC acts globally, regulating expression of genes within SPI-1 and SPI-2 in vitro and in vivo (during infection of mice). Additionally, dopamine β-hydroxylase knockout (Dbh − / −) mice that do not produce Epi or NE showed different susceptibility to Salmonella serovar Typhimurium infection than wild-type mice. These data suggest that the AI-3/Epi/NE signaling system is a key factor during Salmonella serovar Typhimurium pathogenesis in vitro and in vivo. Elucidation of the role of this interkingdom signaling system in Salmonella serovar Typhimurium should contribute to a better understanding of the complex interplay between the pathogen and the host during infection.

scholarly journals Role of two-component sensory systems of Salmonella enterica serovar Dublin in the pathogenesis of systemic salmonellosis in cattle

Microbiology ◽  
2010 ◽  
Vol 156 (10) ◽  
pp. 3108-3122 ◽  
Author(s):  
Gillian D. Pullinger ◽  
Pauline M. van Diemen ◽  
Francis Dziva ◽  
Mark P. Stevens
Keyword(s):  
Salmonella Enterica ◽  
Response Regulator ◽  
Systemic Disease ◽  
Lymphatic Vessels ◽  
Intestinal Barrier ◽  
Systemic Infection ◽  
Oral Route ◽  
Systematic Analysis ◽  
Two Component

Salmonella enterica serovar Dublin (S. Dublin) is associated with enteritis, typhoid and abortion in cattle. Infections are acquired by the oral route, and the bacteria transit through varied anatomical and cellular niches to elicit systemic disease. S. Dublin must therefore sense and respond to diverse extrinsic stimuli to control gene expression in a spatial and temporal manner. Two-component systems (TCSs) play key roles in such processes, and typically contain a membrane-associated sensor kinase (SK) that modifies a cognate response regulator. Analysis of the genome sequence of S. Dublin identified 31 conserved SK genes. Each SK gene was separately disrupted by lambda Red recombinase-mediated insertion of transposons harbouring unique sequence tags. Calves were challenged with a pool of the mutants together with control strains of defined virulence by the oral and intravenous routes. Quantification of tagged mutants in output pools derived from various tissues and cannulated lymphatic vessels allowed the assignment of spatial roles for each SK following oral inoculation or when the intestinal barrier was bypassed by intravenous delivery. Mutant phenotypes were also assigned in cultured intestinal epithelial cells. Mutants with insertions in barA, envZ, phoQ, ssrA or qseC were significantly negatively selected at all enteric and systemic sites sampled after oral dosing. Mutants lacking baeS, dpiB or citA were negatively selected at some but not all sites. After intravenous inoculation, only barA and phoQ mutants were significantly under-represented at systemic sites. The novel role of baeS in intestinal colonization was confirmed by oral co-infection studies, with a mutant exhibiting modest but significant attenuation at a number of enteric sites. This is the first systematic analysis of the role of all Salmonella TCSs in a highly relevant model of enteric fever. Spatial roles were assigned to eight S. Dublin SKs, but most were not essential for intestinal or systemic infection of the target host.

scholarly journals Dormant Intracellular Salmonella enterica Serovar Typhimurium Discriminates among Salmonella Pathogenicity Island 2 Effectors To Persist inside Fibroblasts

2013 ◽  
Vol 82 (1) ◽  
pp. 221-232 ◽  
Author(s):  
Cristina Núñez-Hernández ◽  
Ana Alonso ◽  
M. Graciela Pucciarelli ◽  
Josep Casadesús ◽  
Francisco García-del Portillo
Keyword(s):  
Salmonella Enterica ◽  
Pathogenicity Island ◽  
Effector Proteins ◽  
Intracellular Bacteria ◽  
Secretion Systems ◽  
Cultured Fibroblasts ◽  
Content Type ◽  
Type Iii Secretion Systems ◽  
Serovar Typhimurium

ABSTRACTSalmonella entericauses effector proteins delivered by type III secretion systems (TTSS) to colonize eukaryotic cells. Recentin vivostudies have shown that intracellular bacteria activate the TTSS encoded bySalmonellapathogenicity island-2 (SPI-2) to restrain growth inside phagocytes. Growth attenuation is also observedin vivoin bacteria colonizing nonphagocytic stromal cells of the intestinal lamina propria and in cultured fibroblasts. SPI-2 is required for survival of nongrowing bacteria persisting inside fibroblasts, but its induction mode and the effectors involved remain unknown. Here, we show that nongrowing dormant intracellular bacteria use the two-component system OmpR-EnvZ to induce SPI-2 expression and the PhoP-PhoQ system to regulate the time at which induction takes place, 2 h postentry. Dormant bacteria were shown to discriminate the usage of SPI-2 effectors. Among the effectors tested, SseF, SseG, and SseJ were required for survival, while others, such as SifA and SifB, were not. SifA and SifB dispensability correlated with the inability of intracellular bacteria to secrete these effectors even when overexpressed. Conversely, SseJ overproduction resulted in augmented secretion and exacerbated bacterial growth. Dormant bacteria produced other effectors, such as PipB and PipB2, that, unlike what was reported for epithelial cells, did not to traffic outside the phagosomal compartment. Therefore, permissiveness for secreting only a subset of SPI-2 effectors may be instrumental for dormancy. We propose that theS. entericaserovar Typhimurium nonproliferative intracellular lifestyle is sustained by selection of SPI-2 effectors that are produced in tightly defined amounts and delivered to phagosome-confined locations.

scholarly journals Differences in Host Cell Invasion and Salmonella Pathogenicity Island 1 Expression between Salmonella enterica Serovar Paratyphi A and NontyphoidalS. Typhimurium

2016 ◽  
Vol 84 (4) ◽  
pp. 1150-1165 ◽  
Author(s):  
Dana Elhadad ◽  
Prerak Desai ◽  
Guntram A. Grassl ◽  
Michael McClelland ◽  
Galia Rahav ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Invasion ◽  
Salmonella Enterica ◽  
Intestinal Inflammation ◽  
Pathogenicity Island ◽  
Effector Proteins ◽  
Host Cells ◽  
Host Cell Invasion ◽  
Content Type ◽  
Microaerobic Conditions

Active invasion into nonphagocytic host cells is central toSalmonella entericapathogenicity and dependent on multiple genes withinSalmonellapathogenicity island 1 (SPI-1). Here, we explored the invasion phenotype and the expression of SPI-1 in the typhoidal serovarS. Paratyphi A compared to that of the nontyphoidal serovarS. Typhimurium. We demonstrate that whileS. Typhimurium is equally invasive under both aerobic and microaerobic conditions,S. Paratyphi A invades only following growth under microaerobic conditions. Transcriptome sequencing (RNA-Seq), reverse transcription-PCR (RT-PCR), Western blot, and secretome analyses established thatS. Paratyphi A expresses much lower levels of SPI-1 genes and secretes lesser amounts of SPI-1 effector proteins thanS. Typhimurium, especially under aerobic growth. Bypassing the native SPI-1 regulation by inducible expression of the SPI-1 activator, HilA, considerably elevated SPI-1 gene expression, host cell invasion, disruption of epithelial integrity, and induction of proinflammatory cytokine secretion byS. Paratyphi A but not byS. Typhimurium, suggesting that SPI-1 expression is naturally downregulated inS. Paratyphi A. Using streptomycin-treated mice, we were able to establish substantial intestinal colonization byS. Paratyphi A and showed moderately higher pathology and intestinal inflammation in mice infected withS. Paratyphi A overexpressinghilA. Collectively, our results reveal unexpected differences in SPI-1 expression betweenS. Paratyphi A andS. Typhimurium, indicate thatS. Paratyphi A host cell invasion is suppressed under aerobic conditions, and suggest that lower invasion in aerobic sites and suppressed expression of immunogenic SPI-1 components contributes to the restrained inflammatory infection elicited byS. Paratyphi A.

scholarly journals Coordinated Regulation of Expression of Salmonella Pathogenicity Island 1 and Flagellar Type III Secretion Systems by ATP-Dependent ClpXP Protease

2008 ◽  
Vol 190 (7) ◽  
pp. 2470-2478 ◽  
Author(s):  
Hirokazu Kage ◽  
Akiko Takaya ◽  
Mai Ohya ◽  
Tomoko Yamamoto
Keyword(s):  
Type Iii Secretion ◽  
Stress Protein ◽  
Systemic Infection ◽  
Pathogenicity Island ◽  
Host Cells ◽  
Bacterial Invasion ◽  
Secretion Systems ◽  
Regulation Of Expression ◽  
Type Iii ◽  
Macrophage Apoptosis

ABSTRACT Salmonella enterica serovar Typhimurium delivers a variety of proteins via the Salmonella pathogenicity island 1 (SPI1)-encoded type III secretion system into host cells, where they elicit several physiological changes, including bacterial invasion, macrophage apoptosis, and enteropathogenesis. Once Salmonella has established a systemic infection, excess macrophage apoptosis would be detrimental to the pathogen, as it utilizes macrophages as vectors for systemic dissemination throughout the host. Therefore, SPI1 expression must be restricted to one or a few specific locations in the host. In the present study, we have demonstrated that the expression of this complex of genes is repressed by the ATP-dependent ClpXP protease, which therefore suppresses macrophage apoptosis. Depletion of ClpXP caused significant increases in the amounts of two SPI1-encoded transcriptional regulators, HilC and HilD, leading to the stimulation of hilA induction and therefore activation of SPI1 expression. Our evidence shows that ClpXP regulates cellular levels of HilC and HilD via the control of flagellar gene expression. Subsequent experiments demonstrated that the flagellum-related gene product FliZ controls HilD posttranscriptionally, and this in turn activates HilC. These findings suggest that the ClpXP protease coregulates SPI1-related virulence phenotypes and motility. ClpXP is a member of the stress protein family induced in bacteria exposed to hostile environments such as macrophages.

scholarly journals Mapping the Regulatory Network for Salmonella enterica Serovar Typhimurium Invasion

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Carol Smith ◽  
Anne M. Stringer ◽  
Chunhong Mao ◽  
Michael J. Palumbo ◽  
Joseph T. Wade
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Cross Talk ◽  
Regulatory Network ◽  
Salmonella Enterica ◽  
Expression Profiles ◽  
Pathogenicity Island ◽  
Host Cells ◽  
Environmental Signals ◽  
Regulatory Pathways

ABSTRACT Salmonella enterica pathogenicity island 1 (SPI-1) encodes proteins required for invasion of gut epithelial cells. The timing of invasion is tightly controlled by a complex regulatory network. The transcription factor (TF) HilD is the master regulator of this process and senses environmental signals associated with invasion. HilD activates transcription of genes within and outside SPI-1, including six other TFs. Thus, the transcriptional program associated with host cell invasion is controlled by at least 7 TFs. However, very few of the regulatory targets are known for these TFs, and the extent of the regulatory network is unclear. In this study, we used complementary genomic approaches to map the direct regulatory targets of all 7 TFs. Our data reveal a highly complex and interconnected network that includes many previously undescribed regulatory targets. Moreover, the network extends well beyond the 7 TFs, due to the inclusion of many additional TFs and noncoding RNAs. By comparing gene expression profiles of regulatory targets for the 7 TFs, we identified many uncharacterized genes that are likely to play direct roles in invasion. We also uncovered cross talk between SPI-1 regulation and other regulatory pathways, which, in turn, identified gene clusters that likely share related functions. Our data are freely available through an intuitive online browser and represent a valuable resource for the bacterial research community. IMPORTANCE Invasion of epithelial cells is an early step during infection by Salmonella enterica and requires secretion of specific proteins into host cells via a type III secretion system (T3SS). Most T3SS-associated proteins required for invasion are encoded in a horizontally acquired genomic locus known as Salmonella pathogenicity island 1 (SPI-1). Multiple regulators respond to environmental signals to ensure appropriate timing of SPI-1 gene expression. In particular, there are seven transcription regulators that are known to be involved in coordinating expression of SPI-1 genes. We have used complementary genome-scale approaches to map the gene targets of these seven regulators. Our data reveal a highly complex and interconnected regulatory network that includes many previously undescribed target genes. Moreover, our data functionally implicate many uncharacterized genes in the invasion process and reveal cross talk between SPI-1 regulation and other regulatory pathways. All datasets are freely available through an intuitive online browser.

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