The SPI-1-like Type III secretion system: more roles than you think

Egan, Frank; Barret, Matthieu; O’Gara, Fergal

doi:10.3389/fpls.2014.00034

Cited by 27 publications

(32 citation statements)

References 62 publications

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“…The Salmonella pathogenicity island-1 (SPI-1) encoded T3SS is the most studied and functions primarily in the initial invasion of non-phagocytic cells (33, 34). The SPI-2 T3SS is involved in the maintenance of Salmonella containing vacuoles and bacterial replication within host cells, though it’s structure has not been as extensively characterized (35).…”

Section: The Type III Secretion System – Multiple Targeting Opportunimentioning

confidence: 99%

The Bacterial Type III Secretion System as a Target for Developing New Antibiotics

McShan

Guzman

2014

Chem Biol Drug Des

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Antibiotic resistance in pathogens requires new targets for developing novel antibacterials. The bacterial type III secretion system (T3SS) is an attractive target for developing antibacterials as it is essential in the pathogenesis of many Gram-negative bacteria. The T3SS consists of structural proteins, effectors and chaperones. Over 20 different structural proteins assemble into a complex nanoinjector that punctures a hole on the eukaryotic cell membrane to allow the delivery of effectors directly into the host cell cytoplasm. Defects in the assembly and function of the T3SS render bacteria non-infective. Two major classes of small molecules, salicylidene acylhydrazides and thiazolidinones, have been shown to inhibit multiple genera of bacteria through the T3SS. Many additional chemically and structurally diverse classes of small molecule inhibitors of the T3SS have been identified as well. While specific targets within the T3SS of a few inhibitors have been suggested, the vast majority of specific protein targets within the T3SS remain to be identified or characterized. Other T3SS inhibitors include polymers, proteins and polypeptides mimics. In addition, T3SS activity is regulated by its interaction with biologically relevant molecules, such as bile salts and sterols, which could serve as scaffolds for drug design.

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Section: The Type III Secretion System – Multiple Targeting Opportunimentioning

confidence: 99%

The Bacterial Type III Secretion System as a Target for Developing New Antibiotics

McShan

Guzman

2014

Chem Biol Drug Des

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“…Typhimurium translocator operon to obtain ∼20,000 potential homologs. Extraction of highly divergent alignments and enrichment for those sequences previously recognized as having T3SSs of the Inv/Mxi‐Spa family (Tampakaki, ; Egan et al ., ) from this initial screen identified ∼30 different organisms of interest for generation of Randomized Axelerated Maximum Likelihood (RAxML) trees (Fig. ; Supporting Information Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Past phylogenetic analysis has divided the Inv/Mxi‐Spa family into two sub‐clusters (Marguerettaz et al ., ; Abby and Rocha, ; Barret et al ., ; Egan et al ., ). Together with our data, this argues that at least one new family could be added to the current classification of T3SS.…”

Section: Discussionmentioning

confidence: 99%

Functional relatedness in the Inv/Mxi‐Spa type III secretion system family

Klein

Dave

Raphenya

et al. 2017

Molecular Microbiology

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Type III Secretion Systems (T3SSs) are structurally conserved nanomachines that span the inner and outer bacterial membranes, and via a protruding needle complex contact host cell membranes and deliver type III effector proteins. T3SS are phylogenetically divided into several families based on structural basal body components. Here we have studied the evolutionary and functional conservation of four T3SS proteins from the Inv/Mxi-Spa family: a cytosolic chaperone, two hydrophobic translocators that form a plasma membrane-integral pore, and the hydrophilic 'tip complex' translocator that connects the T3SS needle to the translocon pore. Salmonella enterica serovar Typhimurium (S. Typhimurium), a common cause of food-borne gastroenteritis, possesses two T3SSs, one belonging to the Inv/Mxi-Spa family. We used invasion-deficient S. Typhimurium mutants as surrogates for expression of translocator orthologs identified from an extensive phylogenetic analysis, and type III effector translocation and host cell invasion as a readout for complementation efficiency, and identified several Inv/Mxi-Spa orthologs that can functionally substitute for the S. Typhimurium chaperone and translocator proteins. Functional complementation correlates with amino acid sequence identity between orthologs, but varies considerably between the four proteins. This is the first in-depth survey of the functional interchangeability of Inv/Mxi-Spa T3SS proteins acting directly at the host-pathogen interface.

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“…The SP1-1 family of T3SSs has been found in several animal/human (S. enterica, E. coli, Shigella spp., and Yersinia pestis)-and plant (Erwinia spp., Xanthomonas spp., and P. stewartii)-pathogenic bacteria (45). Additionally, the presence of homologs of the SPI-1 T3SS in insect symbionts, including Hamiltonella defensa and S. glossinidius, implies that SPI-1 may be necessary for persistence inside insect hosts (10,13,45). Similarly, P. stewartii carries an SPI-1 T3SS required for persistence in the gut of its insect vector and successful transmission of the pathogen to its ultimate plant host (14).…”

Section: Discussionmentioning

confidence: 99%

Influence of prgH on the Persistence of Ingested Salmonella enterica in the Leafhopper Macrosteles quadrilineatus

Dundore‐Arias

Groves

Barak

2015

Appl Environ Microbiol

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Phytophagous insects can encounter Salmonella enterica on contaminated plant surfaces and transmit externally adhered and internalized bacteria on and among leaves. Excretion of ingested S. enterica by the leafhopper Macrosteles quadrilineatus has been previously reported; however, the sites of persistence of ingested bacteria remain undetermined. Fluorescence microscopy revealed the presence and persistence of S. enterica in various organs of M. quadrilineatus fed an inoculated diet for 12 h and then moved to two consecutive noninoculated diets for a total of 48 h. Ingested S. enterica was predominantly observed in the filter chamber, midgut, and Malpighian tubules of M. quadrilineatus dissected immediately after acquisition and at 24-and 48-h post-acquisition access periods (post-AAPs). Additionally, we examined the potential roles of the Salmonella pathogenicity island 1 (SPI-1) and SPI-2 type III secretion systems (T3SSs) in the persistence and excretion of ingested S. enterica. In competition assays, a prgH mutant lacking a functional SPI-1 T3SS was recovered at significantly lower levels than the WT in insect homogenates at 24 h post-AAP, and complementation with prgH restored S. enterica persistence in M. quadrilineatus. Moreover, expression of prgH inside M. quadrilineatus was observed up to 48 post-AAP. No differences were observed between the WT and an ssaK mutant lacking a functional SPI-2 T3SS in insect homogenates or between the WT and either mutant in insect excretions. This study provides novel insight into the presence and persistence of S. enterica inside M. quadrilineatus and demonstrates that the SPI-1 T3SS influences the persistence of the pathogen in the gut of a potential vector. Salmonella enterica is the leading cause of bacterial foodborne illness in the United States (1). In the last few decades, salmonellosis outbreaks attributed to S. enterica-contaminated fresh produce have increased, and produce is now considered the most likely vehicle of disease transmission (2). Plant contamination with S. enterica is thought to primarily occur in the field before harvest, and the pathogen has the ability to adhere, colonize, and persist in and on plant surfaces, in some cases for extended periods (3, 4). Domestic and wild animals represent one of the main entry routes for S. enterica to produce fields, where they can directly introduce the bacterial pathogens to plants or agricultural water through excretion of contaminated waste (3). Additionally, synanthropic and coprophagic insects can introduce human bacterial pathogens to produce fields by dispersing bacteria associated with their exoskeletons onto plant surfaces (5). These events increase the chances that phytophagous insects could encounter a human enteric pathogen as a result of feeding or wandering on contaminated plant surfaces. The abundance and distribution of phytophagous insects within agricultural fields suggest that their contamination could influence the dispersal of enteric pathogens in the field (6).The aster leafhopper, Macro...

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The SPI-1-like Type III secretion system: more roles than you think

Cited by 27 publications

References 62 publications

The Bacterial Type III Secretion System as a Target for Developing New Antibiotics

The Bacterial Type III Secretion System as a Target for Developing New Antibiotics

Functional relatedness in the Inv/Mxi‐Spa type III secretion system family

Influence of prgH on the Persistence of Ingested Salmonella enterica in the Leafhopper Macrosteles quadrilineatus

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