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PubMed2006

The enteropathogenic Escherichia coli type III secretion system effector Map binds EBP50/NHERF1: implication for cell signalling and diarrhoea.

Enteropathogenic Escherichia coli (EPEC) is the single most important contributor to child diarrhoea in developing countries. Nevertheless, the mechanism responsible for EPEC diarrhoea remains elusive. Using the yeast two-hybrid system to determine the target host cell protein of the EPEC type III secretion system effector Map led to identification of ezrin/radixin/moesin (ERM)-binding phosphoprotein 50 (EBP50), also known as Na+/H+ exchanger regulatory factor 1 (NHERF1). Protein interaction is mediated by the carboxy-terminal Thr-Arg-Leu (TRL) motif of Map and the PSD-95/Disk-large/ZO-1 domain 1 (PDZ1) of EBP50/NHERF1. Although EBP50/NHERF1 is recruited to site of EPEC adhesion in a Map-independent mechanism, co-immunoprecipitation and immunostaining revealed that Map binds to, induces proteolysis of, and colocalizes with EBP50/NHERF1 during infection of cultured epithelial cells. The TRL motif of Map was involved in Map-induced filopodia formation and brush border elongation on infected HeLa and Caco-2 cells respectively. As EBP50/NHERF1 regulates ion channels in the intestine we assessed the involvement of Map in diarrhoea using the Citrobacter rodentium mouse model of EPEC. We report significantly greater diarrhoea following infections with wild-type C. rodentium compared with C. rodentiumDeltamap. These results provide new insights into the mechanisms of EPEC diarrhoea.

Actins↗

PubMed2007

Adaptation to the host environment: regulation of the SPI1 type III secretion system in Salmonella enterica serovar Typhimurium.

Salmonella enterica invades the intestinal epithelium of the host using a type III secretion system encoded on Salmonella pathogenicity island 1 (SPI1). The bacteria integrate environmental signals from a variety of global regulatory systems to precisely induce transcription of SPI1. The regulatory circuit converges on expression of HilA, which directly regulates transcription of the SPI1 apparatus genes. Transcription of hilA is controlled by a complex feed-forward loop. Regulatory signals feed into the system through post-transcriptional and post-translational control of HilD, which in turn activates HilC and RtsA. These three regulators act in concert to control hilA transcription. The system acts as a switch, ensuring that SPI1 is fully on at the appropriate time.

Adaptation, Physiological↗

PubMed2002

The invasion-associated type III secretion system of Salmonella enterica serovar Typhimurium is necessary for intracellular proliferation and vacuole biogenesis in epithelial cells.

Type III secretion systems (TTSS) are used by Gram-negative pathogens to translocate proteins into eukaryotic host cells. Salmonella enterica serovar Typhimurium (S. Typhimurium) has two of these specialized systems, which are encoded on separate Salmonella pathogenicity islands (SPI-1 and SPI-2) and translocate unique sets of effectors. The specific roles of these systems in Salmonella pathogenesis remain undefined, although SPI-1 is required for bacterial invasion of epithelial cells and SPI-2 for survival/replication in phagocytic cells. However, because SPI-1 TTSS mutants are invasion-incompetent, the role of this TTSS in post-invasion processes has not been investigated. In this study, we have used two distinct methods to internalize a non-invasive SPI-1 TTSS mutant (invA) into cultured epithelial cells: (i) co-internalization with wild-type S. Typhimurium (SPI-1-dependent) and (ii) complementation with the Yersinia pseudotuberculosis invasin (inv) gene (SPI-1-independent). In both cases, internalized invA mutants were unable to replicate intracellularly, indicating that SPI-1 effectors are essential for this process and cannot be complemented by wild-type bacteria in the same cell. Analysis of the biogenesis of SCVs showed that vacuoles containing mutant bacteria displayed abnormal maturation that was dependent on the mechanism of entry. Manipulation of Salmonella-containing vacuole (SCV) biogenesis by pharmacologically perturbing membrane trafficking in the host cell increased intracellular replication of wild-type but not mutant S. Typhimurium This demonstrates a previously unknown role for SPI-1 in vacuole biogenesis and intracellular survival in non-phagocytic cells.

Androstadienes↗

PubMed2005

The type III secretion system of biocontrol Pseudomonas fluorescens KD targets the phytopathogenic Chromista Pythium ultimum and promotes cucumber protection.

The type III secretion system (TTSS) is used by Proteobacteria for pathogenic or symbiotic interaction with plant and animal hosts. Recently, TTSS genes thought to originate from the phytopathogen Pseudomonas syringae were evidenced in Pseudomonas fluorescens KD, which protects cucumber from the oomycete Pythium ultimum (kingdom Chromista/Stramenopila). However, it is not known whether the TTSS contributes to plant protection by the bacterium and, if so, whether it targets the plant or the phytopathogen. Inactivation of TTSS gene hrcV following the insertion of an omega cassette strongly reduced the biocontrol activity of the pseudomonad against P. ultimum on cucumber when compared with the wild type, but had no effect on its root-colonization ability. Analysis of a plasmid-based transcriptional hrpJ'-inaZ reporter fusion revealed that expression in strain KD of the operon containing hrcV was strongly stimulated in vitro and in situ by the oomycete and not by the plant. In vitro, both strain KD and its hrcV mutant reduced the activity level of the pectinase polygalacturonase (a key pathogenicity factor) from P. ultimum, but the reduction was much stronger with the wild type. Together, these results show that the target range of bacterial TTSS is not restricted to plants and animals but also can include members of Chromista/Stramenopila, and suggest that virulence genes acquired horizontally from phytopathogenic bacteria were functionally recycled in biocontrol saprophytic Pseudomonas spp., resulting in enhanced plant protection by the latter.

Artificial Gene Fusion↗

PubMed2005

Functional interactions between type IV secretion systems involved in DNA transfer and virulence.

This paper reports an analysis of the functional interactions between type IV secretion systems (T4SS) that are part of the conjugative machinery for horizontal DNA transfer (cT4SS), and T4SS involved in bacterial pathogenicity (pT4SS). The authors' previous work showed that a conjugative coupling protein (T4CP) interacts with the VirB10-type component of the T4SS in order to recruit the protein-DNA complex to the transporter for conjugative DNA transfer. This study now shows by two-hybrid analysis that conjugative T4CPs also interact with the VirB10 element of the pT4SS of Agrobacterium tumefaciens (At), Bartonella tribocorum (Bt) and Brucella suis (Bs). Moreover, the VirB10 component of a cT4SS (protein TrwE of plasmid R388) could be partially substituted by that of a pT4SS (protein TrwE of Bt) for conjugation. This result opens the way for the construction of hybrid T4SS that deliver DNA into animal cells. Interestingly, in the presence of part of the Bs T4SS the R388 T4SS protein levels were decreased and R388 conjugation was strongly inhibited. Complementation assays between the Trw systems of R388 and Bt showed that only individual components from the so-called 'core complex' could be exchanged, supporting the concept that this core is the common scaffold for the transport apparatus while the other 'peripheral components' are largely system-specific.

Agrobacterium tumefaciens↗

PubMed2006

Expression, purification, crystallization and preliminary crystallographic analysis of MxiH, a subunit of the Shigella flexneri type III secretion system needle.

A monodisperse truncation mutant of MxiH, the subunit of the needle from the Shigella flexneri type III secretion system (TTSS), has been overexpressed and purified. Crystals were grown of native and selenomethionine-labelled MxiH(CDelta5) and diffraction data were collected to 1.9 A resolution. The crystals belong to space group C2, with unit-cell parameters a = 183.4, b = 28.1, c = 27.8 A, beta = 96.5 degrees. An anomalous difference Patterson map calculated with the data from the SeMet-labelled crystals revealed a single peak on the Harker section v = 0. Inspection of a uranyl derivative also revealed one peak in the isomorphous difference Patterson map on the Harker section v = 0. Analysis of the self-rotation function indicates the presence of a twofold non-crystallographic symmetry axis approximately along a. The calculated Matthews coefficient is 1.9 A3 Da(-1) for two molecules per asymmetric unit, corresponding to a solvent content of 33%.

Bacterial Proteins↗

PubMed2007

Shigella chromosomal IpaH proteins are secreted via the type III secretion system and act as effectors.

Shigella possess 220 kb plasmid, and the major virulence determinants, called effectors, and the type III secretion system (TTSS) are exclusively encoded by the plasmid. The genome sequences of S. flexneri strains indicate that several ipaH family genes are located on both the plasmid and the chromosome, but whether their chromosomal IpaH cognates can be secreted from Shigella remains unknown. Here we report that S. flexneri strain, YSH6000 encodes seven ipaH cognate genes on the chromosome and that the IpaH proteins are secreted via the TTSS. The secretion kinetics of IpaH proteins by bacteria, however, showed delay compared with those of IpaB, IpaC and IpaD. Expression of the each mRNA of ipaH in Shigella was increased after bacterial entry into epithelial cells, and the IpaH proteins were secreted by intracellular bacteria. Although individual chromosomal ipaH deletion mutants showed no appreciable changes in the pathogenesis in a mouse pulmonary infection model, the DeltaipaH-null mutant, whose chromosome lacks all ipaH genes, was attenuated to mice lethality. Indeed, the histological examination for mouse lungs infected with the DeltaipaH-null showed a greater inflammatory response than induced by wild-type Shigella, suggesting that the chromosomal IpaH proteins act synergistically as effectors to modulate the host inflammatory responses.

Animals↗

PubMed2006

The YfgL lipoprotein is essential for type III secretion system expression and virulence of Salmonella enterica Serovar Enteritidis.

Salmonella enterica, like many gram-negative pathogens, uses type three secretion systems (TTSS) to infect its hosts. The three TTSS of Salmonella, namely, TTSS-1, TTSS-2, and flagella, play a major role in the virulence of this bacterium, allowing it to cross the intestinal barrier and to disseminate systemically. Previous data from our laboratory have demonstrated the involvement of the chromosomal region harboring the yfgL, engA, and yfgJ open reading frames in S. enterica serovar Enteritidis virulence. Using microarray analysis and real-time reverse transcription-PCR after growth of bacterial cultures favorable for either TTSS-1 or TTSS-2 expression, we show in this study that the deletion in S. enterica serovar Enteritidis of yfgL, encoding an outer membrane lipoprotein, led to the transcriptional down-regulation of most Salmonella pathogenicity island 1 (SPI-1), SPI-2, and flagellar genes encoding the TTSS structural proteins and effector proteins secreted by these TTSS. In line with these results, the virulence of the DeltayfgL mutant was greatly attenuated in mice. Moreover, even if YfgL is involved in the assembly of outer membrane proteins, the regulation of TTSS expression observed was not due to an inability of the Delta yfgL mutant to assemble TTSS in its membrane. Indeed, when we forced the transcription of SPI-1 genes by constitutively expressing HilA, the secretion of the TTSS-1 effector protein SipA was restored in the culture supernatant of the mutant. These results highlight the crucial role of the outer membrane lipoprotein YfgL in the expression of all Salmonella TTSS and, thus, in the virulence of Salmonella. Therefore, this outer membrane protein seems to be a privileged target for fighting Salmonella.

Animals↗

PubMed2026

Unveiling a missing component of the atypical type IV secretion system required for natural transformation of Helicobacter pylori.

Exchange of genetic information by natural transformation shapes bacterial evolution. In Helicobacter pylori it is thought to drive its unusually high recombination rate, which has a crucial role in the evolution of virulence and the propagation of antibiotics resistance genes. While in most cases uptake of the incoming DNA into the periplasm is mediated by type IV pili, in H. pylori this initial step of natural transformation requires ComB, a unique competence-specific type IV secretion system (T4SS). The mechanisms by which ComB mediates DNA uptake are still poorly understood, since T4SS are usually involved in an opposite process of DNA export. Here, we identify a gene (hp1421) that is absolutely required for uptake of the transforming DNA into the periplasm, although distant from the comB operons. We show that hp1421 codes for a hexameric ATPase from the VirB11 family. HP1421 is present in the cytoplasm and interacts with ComB4, another ATPase of the T4SS inner membrane subcomplex. The structural modelling and functional analysis of HP1421 and its interaction with ComB4 indicate that HP1421 is a missing component of the ComB inner-membrane subcomplex that we propose to name ComB11. Phylogenetic analyses show that comB11 is a H. pylori core gene and suggest that the competence-dedicated ComB T4SS was a recent acquisition within Helicobacteraceae. Hence, co-option of the T4SS for DNA transformation requires nearly all the proteins that were previously essential for DNA conjugation.

Helicobacter pylori↗

PubMed2006

PopF1 and PopF2, two proteins secreted by the type III protein secretion system of Ralstonia solanacearum, are translocators belonging to the HrpF/NopX family.

Ralstonia solanacearum GMI1000 is a gram-negative plant pathogen which contains an hrp gene cluster which codes for a type III protein secretion system (TTSS). We identified two novel Hrp-secreted proteins, called PopF1 and PopF2, which display similarity to one another and to putative TTSS translocators, HrpF and NopX, from Xanthomonas spp. and rhizobia, respectively. They also show similarities with TTSS translocators of the YopB family from animal-pathogenic bacteria. Both popF1 and popF2 belong to the HrpB regulon and are required for the interaction with plants, but PopF1 seems to play a more important role in virulence and hypersensitive response (HR) elicitation than PopF2 under our experimental conditions. PopF1 and PopF2 are not necessary for the secretion of effector proteins, but they are required for the translocation of AvrA avirulence protein into tobacco cells. We conclude that PopF1 and PopF2 are type III translocators belonging to the HrpF/NopX family. The hrpF gene of Xanthomonas campestris pv. campestris partially restored HR-inducing ability to popF1 popF2 mutants of R. solanacearum, suggesting that translocators of R. solanacearum and Xanthomonas are functionally conserved. Finally, R. solanacearum strain UW551, which does not belong to the same phylotype as GMI1000, also possesses two putative translocator proteins. However, although one of these proteins is clearly related to PopF1 and PopF2, the other seems to be different and related to NopX proteins, thus showing that translocators might be variable in R. solanacearum.

Amino Acid Sequence↗

PubMed2002

Mutational and transcriptional analysis of the type III secretion system of Bradyrhizobium japonicum.

Sequencing the symbiotic region of Bradyrhizobium japonicum revealed a gene cluster (tts) encoding a type III secretion system (TTSS) that is similar to those found in Mesorhizobium loti MAFF303099 and Rhizobium strain NGR234. In addition to genes that are likely to encode structural core components of the TTSS, the cluster contains several open reading frames that are found exclusively in rhizobia or that are specific to B. japonicum. Depending on the host, mutations within this cluster affected nodulation capacity to different extents. One of the genes likely encodes a transcriptional activator (TtsI) of the two-component regulatory family. Upstream of ttsI, a nod box promoter was identified. Expression of ttsI could be induced by genistein. This induction depended on the transcriptional activator protein NodW as well as the nodD1nodD2nolA gene region. TtsI was found to be involved in transcriptional regulation of the tts gene cluster. Sequence comparison revealed a conserved tts box element within putative promoter regions of several genes. Here, we propose a model of the regulatory cascade leading to the induction of the tts gene cluster.

Bacterial Proteins↗

PubMed2005

HilD, HilC and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonella enterica serovar Typhimurium.

Salmonella enterica serovar Typhimurium invades intestinal epithelial cells using a type three secretion system (TTSS) encoded on Salmonella Pathogenicity Island 1 (SPI1). The SPI1 TTSS injects effector proteins into the cytosol of host cells where they promote actin rearrangement and engulfment of the bacteria. We previously identified RtsA, an AraC-like protein similar to the known HilC and HilD regulatory proteins. Like HilC and HilD, RtsA activates expression of SPI1 genes by binding upstream of the master regulatory gene hilA to induce its expression. HilA activates the SPI1 TTSS structural genes. Here we present evidence that hilA expression, and hence the SPI1 TTSS, is controlled by a feedforward regulatory loop. We demonstrate that HilC, HilD and RtsA are each capable of independently inducing expression of the hilC, hilD and rtsA genes, and that each can independently activate hilA. Using competition assays in vivo, we show that each of the hilA regulators contribute to SPI1 induction in the intestine. Of the three, HilD has a predominant role, but apparently does not act alone either in vivo or in vitro to sufficiently activate SPI1. The two-component regulatory systems, SirA/BarA and OmpR/EnvZ, function through HilD, thus inducing hilC, rtsA and hilA. However, the two-component systems are not responsible for environmental regulation of SPI1. Rather, we show that 'SPI1 inducing conditions' cause independent activation of the rtsA, hilC and hilD genes in the absence of known regulators. Our model of SPI1 regulation provides a framework for future studies aimed at understanding this complicated regulatory network.

Animals↗

PubMed2004

Complete type III secretion system of a mesophilic Aeromonas hydrophila strain.

We have investigated the existence and genetic organization of a functional type III secretion system (TTSS) in a mesophilic Aeromonas strain by initially using the Aeromonas hydrophila strain AH-3. We report for the first time the complete TTSS DNA sequence of an Aeromonas strain that comprises 35 genes organized in a similar disposition as that in Pseudomonas aeruginosa. Using several gene probes, we also determined the presence of a TTSS in clinical or environmental strains of different Aeromonas species: A. hydrophila, A. veronii, and A. caviae. By using one of the TTSS genes (ascV), we were able to obtain a defined insertion mutant in strain AH-3 (AH-3AscV), which showed reduced toxicity and virulence in comparison with the wild-type strain. Complementation of the mutant strain with a plasmid vector carrying ascV was fully able to restore the wild-type toxicity and virulence.

Aeromonas↗

PubMed2006

Yersinia has a tropism for B and T cell zones of lymph nodes that is independent of the type III secretion system.

Pathogenic Yersinia have a pronounced tropism for lymphatic tissues and harbor a virulence plasmid that encodes a type III secretion system, pTTSS, that transports Yops into host cells. Yops are critical virulence factors that prevent phagocytosis by macrophages and neutrophils and Yersinia mutants lacking one or more Yops are defective for survival in lymphatic tissues, liver, and gastrointestinal tract. However, here we demonstrate that Y. pseudotuberculosis (Yptb) mutants lacking the pTTSS survived as well as or better than wild-type (WT) Yptb in the mesenteric lymph nodes (MLN). Infection with pTTSS mutants caused lymphadenitis with little necrosis, whereas infection with WT Yptb provoked lymphadenitis with multiple necrotic suppurative foci. Gentamicin protection assays and microscopic examination of the MLN revealed that pTTSS mutants resided extracellularly adjacent to B and T lymphocytes in the cortex and paracortex. WT Yptb was found extracellularly adjacent to neutrophils and macrophages in necrotic areas and adjacent to B and T lymphocytes in less-inflamed areas. To determine whether lymphocytes protected pTTSS mutants from phagocytic cells, Rag1(-/-) mice were infected with pTTSS mutants or WT Yptb. pTTSS mutants but not WT, were impaired for survival in MLN of Rag1(-/-) mice, suggesting that lymphocyte-rich regions constitute a protective niche for pTTSS mutants. Finally, we show that invasin and the chromosomally encoded TTSS were not required for Yptb survival in MLN. In summary, chromosomally encoded factors are sufficient for Yptb replication in the cortex and paracortex of MLN; the pTTSS enables Yersinia to survive within phagocyte-rich areas of lymph nodes, and spread to other tissues.

Adhesins, Bacterial↗

PubMed2003

Genotypic and phenotypic analysis of type III secretion system in a cohort of Pseudomonas aeruginosa bacteremia isolates: evidence for a possible association between O serotypes and exo genes.

The type III secretion system (TTSS) of Pseudomonas aeruginosa was characterized genetically and phenotypically in 92 epidemiologically unrelated bacteremic strains. Four groups of strains (TTSS types) were defined according to the level of type III protein secretion and kinetics of cytotoxicity. Type 1 strains (n=26) were highly and rapidly cytotoxic and secreted ExoU, type 2 strains (n=48) exhibited slower cytotoxic rates and expressed ExoS but not ExoU, type 3 strains (n=14) were poorly cytotoxic, and type 4 strains (n=4) were not cytotoxic. Type 3 and 4 strains did not have detectable secretion phenotype; however, some type 4 strains were able to reach a level of cytotoxicity similar to that of type 1 and type 2 strains when complemented in trans by a functional exsA gene. A statistically significant association (P<.001) was found between TTSS types and detection of the mutually exclusive exoU and exoS genes. In addition, 24 of 25 serotype O:1, O:10, and O:11 strains contained exoU, whereas 54 of 55 serotype O:3, O:4, O:6, O:12, and O:16 strains contained exoS (P<.001). Our results demonstrate correlations among exoU or exoS genotype, TTSS phenotype, and O serotype in bacteremic P. aeruginosa isolates.

ADP Ribose Transferases↗

PubMed2006

Expression of and secretion through the Aeromonas salmonicida type III secretion system.

Aeromonas salmonicida subsp. salmonicida is the aetiological agent of furunculosis, a disease of farmed and wild salmonids. The type III secretion system (TTSS) is one of the primary virulence factors in A. salmonicida. Using a combination of differential proteomic analysis and reverse transcriptase (RT)-PCR, it is shown that A. salmonicida A449 induces the expression of TTSS proteins at 28 degrees C, but not at its more natural growth temperature of 17 degrees C. More modest increases in expression occur at 24 degrees C. This temperature-induced up-regulation of the TTSS in A. salmonicida A449 occurs within 30 min of a growth temperature increase from 16 to 28 degrees C. Growth conditions such as low-iron, low pH, low calcium, growth within the peritoneal cavity of salmon and growth to high cell densities do not induce the expression of the TTSS in A. salmonicida A449. The only other known growth condition that induces expression of the TTSS is growth of the bacterium at 16 degrees C in salt concentrations ranging from 0.19 to 0.38 M NaCl. It is also shown that growth at 28 degrees C followed by exposure to low calcium results in the secretion of one of the TTSS effector proteins. This study presents a simple in vitro model for the expression of TTSS proteins in A. salmonicida.

Aeromonas salmonicida↗

PubMed1994

[The effect of occult hyperprolactinemia (OHP) on gonadotropin secretion system].

The present study was conducted to investigate the effects of the transient increase of serum prolactin levels on the gonadotropin secretion system in patients with occult hyperprolactinemia (OHP). 216 cases of normoprolactinemic hypothalamic anovulatious were selected by LH-RH and TRH loading tests, and 5mg/day of bromocriptine was administered for more than 8 weeks. The effectiveness of the bromocriptine administration was estimated by the ultrasonic examination of the follicular development. The endocrinological backgrounds were compared between bromocriptine effective (154 cases, group A) and non-effective (62 cases, group B) patients. Serum prolactin levels 30min. after LH-RH and TRH loading (PRL30 in group A were significantly higher than those of group B (74.1 +/- 36.5 vs. 38.0 +/- 18.2ng/ml, p < 0.01). From this result, it was thought that many of the OHP patients were selected in group A. Serum LH levels 30min. after loading test (LH30) in group A also increased compared to those of group B (65.0 +/- 66.5 vs. 43.1 +/- 34.3mIU/ml, p < 0.02). The LH/FSH ratio before loading was also higher in group A (1.3 +/- 0.6) than that of group B (1.0 +/- 0.5, p < 0.02). This fact showed that group A also contained patients with hyper-LH hypothalamic anovulation, which is known as the endocrinological PCOD. There were also significant inverse correlations between serum levels of prolactin and FSH in group A (before loading values: r = 0.272, 30min. after loading: r = 0.224, p < 0.01). By the administration of bromocriptine, serum prolactin levels decreased both in group A and B, and the elevated serum LH/FSH ratio (1.0 +/- 0.4, p < = 0.02), LH30 (46.1 +/- 37.0mIU/ml, p < 0.005) also decreased significantly. Serum levels of FSH in group A increased significantly with treatment (before loading: 5.4 +/- 2.6-->6.2 +/- 2.0, 30min. after loading: 10.6 +/- 6.0-->14.6 +/- 9.9mIU/ml, p < 0.005). From these facts, it was concluded that FSH secretion was suppressed even by a slight increase of serum prolactin levels which was usually seen in the OHP, and bromocriptine administration was effective not only for the suppression of serum prolactin and LH levels, but also for the improvement of FSH secretion in the OHP patients.

Anovulation↗

PubMed2004

The ATP-dependent ClpXP and Lon proteases regulate expression of the Yersinia pestis type III secretion system via regulated proteolysis of YmoA, a small histone-like protein.

The Yersinia pestis plasmid pCD1-encoded type III secretion system (T3SS) is essential for the pathogenicity of Y. pestis in mammalian hosts. T3SS-associated genes are maximally expressed at 37 degrees C in the absence of extracellular calcium. Expression of T3SS genes requires LcrF, an AraC-like transcriptional activator, and is repressed by YmoA, a small histone-like protein. The mechanism by which temperature regulates T3SS gene expression has not been determined; however, changes in DNA topology have been implicated in this process. We report here that a Y. pestis strain deficient in production of the ClpXP and Lon proteases does not express a functional T3SS partly because of high cytosolic levels of YmoA. YmoA is rapidly degraded at 37 degrees C in wild-type Y. pestis, but remains stable in a clpXPlon deletion mutant. The stability of YmoA in wild-type Y. pestis increased as the growth temperature of the culture decreased; in contrast, YmoA was stable at all temperatures examined in the clpXPlon deletion mutant. These results indicate that the ClpXP and Lon proteases contribute to the environmental regulation of the Y. pestis T3SS system through regulated proteolysis of YmoA.

Adaptation, Physiological↗