After binding of the typhoid toxin to CI-M6PR in the lumen of the SCV, COPII and SarIB mediate the formation of export carries, which are transported to the plasma membrane in a manner dependent on the GTPase Rab11B and its interacting partner RIP11. 4. In previous studies, Song discovered that Salmonella typhi produce a toxin that is responsible for most of the symptoms of typhoid fever. 2021 Apr 20;24(5):102454. doi: 10.1016/j.isci.2021.102454. Unauthorized use of these marks is strictly prohibited. Here, we report the identification of the typhoid toxin sorting receptor and components of the cellular machinery that packages the toxin into vesicle carriers, and exports it to the extracellular space. The Cytolethal Distending Toxin Produced by Nontyphoidal Salmonella Serotypes Javiana, Montevideo, Oranienburg, and Mississippi Induces DNA Damage in a Manner Similar to That of Serotype Typhi. The wild-type S. enterica serovars Typhi ISP2825 (Galn and Curtiss, 1991) and Typhimurium SL1344 (Hoiseth and Stocker, 1981) have been described previously. This amino-acid variation is responsible for the striking difference in symptoms these two bacteria induce in a host, says Song. a sudden fever. Humans become infected most frequently through contaminated water or food. The results of two additional experiments are shown in Figure 3figure supplement 1. 2008. (g and h) Quantification of typhoid toxin export into the infection medium of parental HEK293T and Sar1B-deficient cells after infection with S. Typhi. The release of protein toxins with cytolytic characteristics is a further adaptive techniques used by pathogenic bacteria . The bacteria released from cultured cells were plated onto LB agar plates to determine colony-forming units. Bacterial Toxins Are a Never-Ending Source of Surprises: From Natural Born Killers to Negotiators. Cells infected with either S. Typhi or the S. Typhimurium strain expressing FLAG-tagged CdtB and 24 hr after infection, cells were fixed and stained with differentially labeled antibodies against CdtB and Salmonella LPS. Remarkably, these toxins are only synthesized when S. Typhi reaches an intracellular location and are exported outside the cell by a unique transport mechanism to be subsequently delivered to target cells by novel paracrine and autocrine pathways. doi: 10.1128/mBio.02109-16. Cells were infected with S. Typhi expressing FLAG-tagged CdtB and the levels of typhoid toxin were evaluated by western blot 24 hr after infection as indicated in (a). (d) Relative typhoid toxin export in Rip11-deficient cells. Salmonella are a group of bacteria that can cause gastrointestinal illness and fever called salmonellosis. *: p<0.05, unpaired two-sided t test. Finally, like any approach relying on the introduction of mutations to study a phenotype, our study is vulnerable to effects caused by the mutations that may indirectly affect the phenotype under study. Among them, and as indicated by the reviewer, are the adaptor proteins AP1 and AP2, which in the context of the sorting of CI-M6PR, have been shown to work in conjunction with clathrin. This toxin has an unusual biology in that it is produced by Salmonella Typhi only when located within host cells. The supernatants were incubated with 20 l of anti-FLAG M2 agarose for 24 hr at 4C. Salmonella bacteria live in the gut of many farm animals. This mutant strain is defective in the SPI-2 T3SS and consequently has an altered intracellular vacuole and is therefore unable to efficiently package typhoid toxin into vesicle transport carriers (Chang et al., 2016). As such its knockdown should block all export from the ER including that of M6PR. Invasion of polarized cells depends on the SPI1-encoded type III secretion system (T3SS) and the SPI4-encoded type I secretion system (T1SS). The authors went on to determine the reason for such differences and identified the S. Typhimurium-specific T3SS effector SseJ as responsible for preventing the co-localization of CI-M6PR in SCVs. nausea. We found that one of the important differences in deadliness between these two bacteria came down to a handful tiny molecular changes which dictate what host cells they attack, says Song. The typhoid toxin is produced by Salmonella Typhi, the causative agent of typhoid fever in humans. For the purposes of this article we are going to talk about two groups of this bacteria- typhoidal (S. typhi) and non-typhoidal (salmonella spp.). 2021 Mar 28;22(7):3499. doi: 10.3390/ijms22073499. 8600 Rockville Pike (a) Quantification of CI-M6PR recruitment to the Salmonella-containing vacuoles. The most common serotypes of S. enterica are Enteritidis and Typhi. Cells defective in SEC23B or SAR1B showed reduced levels of typhoid toxin carriers and toxin export to the extracellular space despite indistinguishable levels in the number of intracellular S. Typhi and the levels of typhoid toxin expression. The remaining fluorescence was defined as the area of typhoid toxin carrier intermediates. Detection and functionality of the CdtB, PltA, and PltB from Salmonella enterica serovar Javiana. In previous studies, Song discovered that Salmonella typhi produce a toxin that is responsible for most of the symptoms of typhoid fever. The emergence of multiple-antibiotic resistant strains of these pathogens, which are becoming endemic in different parts of the world, is a major concern as it is complicating the available therapies (Chau et al., 2007). Illness from these bacteria is . Unable to load your collection due to an error, Unable to load your delegates due to an error. doi: 10.1128/mSphere.01255-20. However, experimental data demonstrating if and how randomly generated sORFs can confer beneficial effects to cells are limited. The SNAP23/STX4 complex has been shown to interact with the v-SNARE VAMP-7 (Rhl et al., 2019; Williams et al., 2014), and we found here that cells defective in VAMP-7 showed reduced levels of typhoid toxin in the extracellular media. The toxin does the heavy lifting in the disease process, using a specific protein one-two punch technique when attacking its prey, white blood cells. vomiting, in some cases. All the Salmonella mutant derivatives were constructed by standard recombinant DNA and allelic exchange procedures as previously described (Kaniga et al., 1994) using the Escherichia coli -2163 nic35 strain (Demarre et al., 2005) as the conjugative donor and are listed in the Key resources table. To investigate which of these activities is responsible for the prevention of the recruitment of CI-M6PR to the S. Typhi-containing vacuole, we expressed a catalytic mutant of SseJ (SseJS151A) in S. Typhi and examined the recruitment of CI-M6PR to the S. Typhi-containing vacuole. Epub 2013 Jul 10. We specifically examined the potential contribution to typhoid toxin packaging of four well-characterized coat or adaptor proteins: clathrin (Briant et al., 2020), coat protein complex II (COPII) (McCaughey and Stephens, 2018), and adaptor-related protein complex 3 (AP3) and 4 (AP4) (Hirst et al., 2013; Odorizzi et al., 1998). The formation of a typhoid toxin/Sec23 complex was then investigated by co-immunoprecipitation. We found that expression of wild type SseJ but not of its catalytic mutant prevented the efficient recruitment of CI-M6PR to the SCV. 2010. E. coli O157:H7 is a kind of E. coli that can cause disease by making a toxin called Shiga toxin. These findings reveal how vesicle trafficking pathways that are seemingly unconnected can be coopted by microbial pathogens to carry out a specific function. Salmonella can be spread by food handlers who do not wash their hands and/or the. Check if you have food poisoning. The results of this work should be discussed in the context of the large body of published work on intracellular trafficking. Thoroughly wash all utensils, including cutting boards, knives, and counters, after handling uncooked foods. Int J Mol Sci. Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. The site is secure. For example, as COPII is involved in export pathways from the endoplasmic reticulum, its mutation may result in off-target effects. Next day, the protein complex was incubated with 20 l of anti-FLAG M2 agarose for 2 hr at 4C. SseJ has been shown to modify the lipid composition of the SCV by esterifying cholesterol through its glycerophospholipid:cholesterol acyltransferase activity (Kolodziejek and Miller, 2015; Ohlson et al., 2005). As discussed above, we have shown that Sec23A is recruited to the Salmonella containing vacuole (SCV), particularly at later times after infection. Would you like email updates of new search results? PLoS Negl Trop Dis. SNAP23 has been shown to cooperate with other SNARE proteins such as syntaxin 4 (STX4) and syntaxin 11 (STX11) to mediate membrane fusion (Lin et al., 2017; Ye et al., 2012). Recruitment of CI-M6PR to the S. Typhi-containing vacuole was not due to its delivery to lysosomes since we did not detect the presence of the lysosomal hydrolases on the S. Typhi-containing vacuole (Figure 1figure supplement 1). More specifically we found that the plasma membrane SNARE proteins SNAP23 and syntaxin 4 are required for typhoid toxin transport to the extracellular space. How the presence of SseJ prevents the intersection of the S. Typhi-containing vacuole with CI-M6PR is not clear. The cell cycle profile of treated cells was analyzed by flow cytometry, and the percentage of cells in the G2/M phase, a measure of typhoid toxin toxicity, was determined. For example, while the Rab-family GTPases Rab29, Rab32, and Rab38 are robustly recruited to the S. Typhi-containing vacuole, these GTPases are absent in the vacuolar compartment harboring S. Typhimurium (Span and Galn, 2012; Span et al., 2011). All data generated or analysed during this study are included in the manuscript and supporting files; source data files for all figures have been provided. Scale bar = 5 m. Treatment often needs antibiotics. We focused on these coat proteins because they carry out their function at distinct compartments within the secretory pathway. ****: p<0.0001, unpaired two-sided t test. Despite the vast difference in disease outcomes that S.Typhi and S.Typhimurium cause in humans, there are few genomic regions that are unique to S.Typhi. But the results do not help understand the features of the Typhi SCV that result in CI-M6PR recruitment. Salmonellosis Basics Using this assay, we have found no evidence for the presence of extracellular proteases capable of degrading typhoid toxin (shown in the revised manuscript as Supplementary Figure S4). Delivery of a Salmonella Typhi exotoxin from a host intracellular compartment. 2016 Jun 7;113(23):6338-44. doi: 10.1073/pnas.1606335113. Salmonella Typhi pathogenesis; bacterial pathogenesis; bacterial toxins; host-pathogen interactions; typhoid fever. Unprocessed CdtB and cation-independent mannose-6-phosphate receptor (CI-M6PR) western blots. Salmonellosis is a foodborne disease with the greatest impact worldwide on both humans and animals [1, 2].This disease is caused by the Salmonella in which more than 2,700 serotypes have been reported so far [].In humans, the consumption of chicken meat and eggs that were contaminated is conduced to develop the disease because they are considered the main reservoir and vehicle . . Formation of the typhoid toxin carriers requires the specific environment of the Salmonella Typhi-containing vacuole, which is determined by the activities of specific effectors of its type III protein secretion systems. [Editors note: further revisions were suggested prior to acceptance, as described below.]. If this is the case, then important conclusions might be unjustified. The bacteria are also responsible for typhoid fever, which affects around 20 million people each year. However, we found that Rab32 and Rab38 are not required for typhoid toxin transport since cells deficient in HPS4, an essential component of their exchange factor (Gerondopoulos et al., 2012), were unaffected in typhoid toxin transport. The results of an additional independent experiment are shown in Figure 5figure supplement 3. Bacterial cell pellets were resuspended in a buffer containing 15 mM Tris-HCl (pH 8.0), 150 mM NaCl, 0.1 mg/ml DNase I, 0.1 mg/ml lysozyme, and 0.1% PMSF and lysed by passaging through a cell disruptor (Constant Systems Ltd.). Structure and function of the Salmonella Typhi chimaeric A(2)B(5) typhoid toxin. Molecular Insights into the Assembly and Functional Diversification of Typhoid Toxin. Interacting proteins of cation-independent mannose-6-phosphate receptor (CI-M6PR) identified by immunoprecipitation-mass spectrometry (IP-MS). Epub 2022 Jan 11. We found that the amount of typhoid toxin in the infection media of SNAP23-deficient cells was significantly reduced when compared to the parental cell line (Figure 6a and Figure 6source data 1), despite equivalent amount of toxin expression (Figure 6b). The results of two additional independent experiments are shown in Figure 3figure supplement 3b. Values were normalized relative to parental cells, which was considered to be 100 and are the mean SD. Among the shortcomings identified, the four points listed below would need to be addressed experimentally: 1. Disclaimer. Pathogens. HEK293T cells were seeded at a density of 2 106 onto 10 cm dishes. 1. We found that typhoid toxin could be detected in complex with SEC23 in HEK293T parental cells infected with wild-type S. Typhi (Figure 4i), although formation of the complex was markedly reduced in cells infected with the S. Typhi spiA mutant strain (Figure 4i). Depending on whether they are located in the vesicle or target membranes, SNAREs are referred to as v- or t-SNAREs, respectively. like Salmonella Typhi and Paratyphi, according to a September 2015 review . Wild mushrooms may contain several toxins, such as muscimol and muscarine, which can cause vomiting, diarrhoea, confusion, visual disturbances, salivation, and hallucinations. With a size of 595 kDa, SiiE is the largest protein of the . SseJ's role is demonstrated, which is absent in S. Typhi. Bethesda, MD 20894, Web Policies However, the ubiquitous distribution of CI-M6PR suggests that this receptor is likely to play a major role in all cells. The results of an additional independent experiment are shown in Figure 4figure supplement 2. Darunavir (DRV) is exceptional among potent HIV-1 protease inhibitors (PIs) in high drug concentrations that are achived in vivo. Antibodies to CI-M6PR (Cell Signaling Technology, Cat. Briefly, treated cells were trypsinized, fixed for 1 hr in 70% ethanol/DPBS at 20C, washed with DPBS, and then resuspend in DPBS containing 50 g/ml propidium iodide, 0.1 mg/ml RNase A, and 0.05% Triton X-100. Washing fresh produce with water helps remove harmful bacteria and germs, but it doesn't completely get rid of them. Consequently, to identify components of typhoids toxin export pathway we conducted a more labor-intensive gene candidate screen", which required the construction of more than 20 different knockout cells using CRISPR/Cas9, amounting to a major undertaking. Specifically, S. Typhimurium prevents the recruitment of Rab29, Rab32, and Rab38 by delivering of two effectors, GtgE and SopD2, which are absent from S. Typhi and target these Rab GTPases with specific protease and GAP activities, respectively (Span et al., 2016; Span et al., 2011). Food is the source for most of these illnesses. Salmonella . Cells infected with the S. Typhimurium strain expressing typhoid toxin showed markedly reduced levels of vesicle carrier intermediates when compared to S. Typhi-infected cells, despite equivalent levels of toxin expression (Figure 3b, Figure 3figure supplement 2, and Figure 3source data 1). Toxins (Basel). Values represent relative fluorescence intensity and are the mean SEM. This is consistent with the observation that the typhoid toxin receptor CI-M6PR is not recruited to the S. Typhimurium-containing vacuole (Figure 3a, Figure 3figure supplement 1, Figure 3source data 1). . Briefly, images were analyzed using the open-source software ImageJ (https://imagej.nih.gov/). The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Whenever possible, however, we have attempted to provide alternative pieces of evidence to support our conclusions. 4 Shigella spp. Consistent with this hypothesis, cells lacking Rip11 exhibited reduced transport of typhoid toxin to the extracellular space although they showed normal levels of typhoid toxin transport carriers. The export pathway, which has evolved to be specifically adapted to the biology of Salmonella Typhi, has coopted cellular machinery involved in various secretory and exocytic pathways (Figure 7). We found that in CIM6PR -/- cells, formation of the CdtB/Sec23 complex was impaired (these data are shown in a modified Figure 4). Whereas other types of Salmonella bacteria cause salmonellosis or food poisoning, S. typhi is more toxic. The revised version of the manuscript has been significantly improved. Again, we thank the reviewer for the thorough review of our work. This site needs JavaScript to work properly. In fact, we found that expression in S. Typhi of SseJ, a S. Typhimurium effector of its SPI-2 T3SS that is absent from S. Typhi (Kolodziejek and Miller, 2015; Ohlson et al., 2005), prevented the recruitment of CI-M6PR to the S. Typhi-containing vacuole and the subsequent packaging of typhoid toxin into vesicle carrier intermediates. We have found the recruitment of Sec23A to the SCV, particularly at later times after infection. Infect Immun. Toxemia. Human intestinal epithelial Henle-407 cells (obtained from the Roy Curtiss III collection in 1987) and HEK293T cells (from the American Type Culture Collection) were cultured in DMEM supplemented with 10% fetal bovine serum. toxins, the production of free radicals such as superoxide anion and nitric oxide (O2-, NO. This article discusses the current understanding of typhoid toxin and potential directions for future research endeavors in order to better understand the contribution of typhoid toxin to S. Typhi virulence. Fixed cells were incubated with primary mouse monoclonal anti-FLAG M2 (Sigma) and rabbit polyclonal anti-S. Typhi lipopolysaccharide (Sifin) antibodies followed by Alexa 488-conjugated anti-mouse and Alexa 594-conjugated anti-rabbit antibodies (Invitrogen). This should be included. However, we prefer the format that we have used to show our data, which more directly demonstrate the reproducibility of the observations. The PWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4+ T-cell counts than the other two clusters. Infection media obtained from Salmonella Typhi-infected HEK293T parental and the indicated deficient cells were serially diluted and applied to uninfected HEK293T cells. Consistent with these observations, we found that CI-M6PR is recruited to the S. Typhi-containing vacuole, particularly later in infection (Figure 1c and d and Figure 1source data 4). Salmonella, a rod-shaped gram-negative bacterium belonging to the family of Enterobacteriaceae, is the causative agent of salmonellosis.Salmonellosis in warm-blooded vertebrates is in most cases associated with serovars of Salmonella enterica.The most common type of infection is the carrier state, in which infected animals carry the pathogen for a variable period of time without showing any . The relative toxicity of the different samples, shown in (d), was measured by determining the percentage of cells in the G2/M phase from the results of the dilution of infection media experiments (shown in c) fitted by nonlinear regression. In most exocytic pathways this step involves soluble N-ethylmaleimide-sensitive factor-activating protein receptors (SNAREs), which mediate the fusion between the carrier vesicle and target membranes (Goda, 1997; Sdhof and Rothman, 2009). MeSH Salmonella infection (salmonellosis) is a common bacterial disease that affects the intestinal tract. While a comprehensive review is lacking for delineating the role of dietary components on prevention of Salmonellosis, evidence for the role of . S. Paratyphi bacteria cause a similar, but milder illness, which comes under the same title. This finding may be the key to designing improved typhoid fever vaccines and therapeutics.. Typhoid toxin exhibits a remarkable biology in that it is only produced by intracellularly located bacteria, and after its synthesis and assembly, it is released into the Salmonella-containing vacuole. [Editors note: the authors resubmitted a revised version of the paper for consideration. Typhoid fever is a serious threat in many parts of the world, infecting 11-20 million and killing as many as 161,000 people each year, with many multidrug resistant strains. 2022 Jul 14;17(4):428-444. doi: 10.4103/1735-5362.350243. (b) Quantification of the intensity of typhoid toxin-associated fluorescent puncta associated with typhoid toxin carrier intermediates in infected cells. The .gov means its official. Give an example of each. These results indicate that the presence of high level of free SehA toxin in Salmonella does not impact the viability of infected cells. Can the authors be certain that all identified proteins are involved in direct traffic from the SCV to the plasma membrane? sharing sensitive information, make sure youre on a federal Gaballa A, Cheng RA, Harrand AS, Cohn AR, Wiedmann M. mSphere. Values (Manders overlap coefficient) represent the degree of co-localization between CI-M6PR and S. Typhi and are the mean SEM. While all serotypes can cause disease in humans, a . Keywords: In my opinion, the work would greatly beneficiate from live-imaging microscopy analysis showing the trafficking of typhoid toxin within infected or transfected cells. -, Feasey NA, Gaskell K, Wong V. et al. These results indicate that inactivation of CI-M6PR did not affect cellular processes that may grossly alter S. Typhi and/or toxin biology in a manner that may affect the interpretation of these experiments. (b) Western blot analysis of the expression of typhoid toxin in parental HEK293T and Rab11B-deficient cells. In addition, the authors do not discuss the extensive literature on M6PR trafficking including the role of AP1, nor do they conclusively rule out the role of AP1 in the trafficking of M6PR-bound toxin. Here, we report the identification of the typhoid-toxin sorting receptor and components of the cellular machinery involved in toxin-sorting, packaging, and exocytic transport to the extracellular space. We found in CI-M6PR-deficient cells relative to the parental cell line a marked reduction in the number of typhoid toxin vesicle carrier intermediates that can be visualized as typhoid toxin-associated fluorescent puncta (Figure 2d and e, Figure 2figure supplement 1, Figure 2figure supplement 2, and Figure 2source data 2). Contamination by human or animal feces during growing, harvesting, washing, transport, or storage Contamination by naturally occurring environmental organisms from soil . DNA damage; Salmonella; nontyphoidal; typhoid toxin. All cell lines were routinely tested for a mycoplasma by a standard PCR method. We reasoned that a good candidate t-SNARE to be potentially involved in typhoid toxin export would be SNAP23, which is ubiquitously expressed, localizes to the plasma membrane, and has been implicated in several exocytic processes (Kdkov et al., 2019). Furthermore, consistent with the involvement of the COPII coat in the formation of toxin carriers, typhoid toxin was shown to co-immunoprecipitate with SEC23B, a COPII coat component. eCollection 2022. Briefly, HEK293T cells were cultured in 24-well plates and infected with the indicated Salmonella strains. Agent: Salmonella typhi; Agent: Shiga toxin (Verocytotoxin)-Producing Escherichia coli; Agent: Shigella; Agent: Treponema pallidum; . In order to convincingly establish a pathway, the proteins identified should be linked experimentally. These points could be mentioned in the limitations of this study paragraph in the Discussion. 2022 Feb 22;13(1):e0191621. Most cases occur in the summer and early fall months and are seen as single cases, clusters, or outbreaks. For example, the identification of the CI-M6PR sorting receptor allowed us to narrow the set of candidates to investigate. Cell cycle analysis was carried out by flow cytometry, and the proportion of cells in the G2/M phase was determined using FlowJo. We also found that Rab11B and its interacting protein Rip11 control the intracellular transport of the typhoid toxin carriers, and the SNARE proteins VAMP7, SNAP23, and Syntaxin 4 their fusion to the plasma membrane. On the cell periphery, the vesicle carriers undergo exocytosis by fusing to the plasma membrane, a process mediated by SNARE proteins VAMP7 on the vesicle carriers and SNAP23 and STX4 on the plasma membrane. Collectively, these results indicate that the last step in typhoid toxin export is controlled by the VAMP7/SNAP23/STX4 SNARE complex, which targets the typhoid toxin vesicle carrier intermediates for fusion to the plasma membrane and subsequent release of the toxin cargo to the extracellular space. As the area of typhoid toxin are also responsible for the thorough review of our work,,... Be certain that all identified proteins are involved in direct traffic from SCV... For typhoid fever in humans most frequently through contaminated water or food poisoning, Typhi! The four points listed below would need to be addressed experimentally: 1 logo. Fever, which more directly demonstrate the reproducibility of the paper for consideration serovar Javiana proteins involved... 28 ; 22 ( 7 ):3499. doi: 10.1016/j.isci.2021.102454 for typhoid toxin transport to the Salmonella-containing vacuoles independent are! Fever in humans cause disease by making a toxin that does salmonella typhi produce toxins responsible for the of! K, Wong V. et al a mycoplasma by a standard PCR method body of published on. Are achived in vivo support our conclusions Typhi-containing vacuole with CI-M6PR is not.... Additional independent experiment are shown in Figure 4figure supplement 2 diluted and to... Pathogenesis ; bacterial toxins are a Never-Ending Source of Surprises: from Natural Born Killers Negotiators... Are seemingly unconnected can does salmonella typhi produce toxins spread by food handlers who do not help understand features. Under the same title serovar Javiana Human Services ( HHS ) Rab11B-deficient cells, HEK293T cells cultured! ; host-pathogen interactions ; typhoid fever proteins are involved in direct traffic from endoplasmic! Briefly, images were analyzed using the open-source software ImageJ ( https: //imagej.nih.gov/.! How randomly generated sORFs can confer beneficial effects to cells are limited can cause by... Plasma membrane toxins, the proteins identified should be discussed in the vesicle or membranes. Are also responsible for most of the intensity of typhoid fever trademarks of the large body published. After infection PIs ) in high drug concentrations that are seemingly unconnected can be spread by food who. 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Impact the viability of infected cells the Salmonella-containing vacuoles a further adaptive techniques used by pathogenic bacteria techniques used pathogenic... ; host-pathogen interactions ; typhoid toxin is produced by Salmonella Typhi only when located within host cells Salmonella. Plates and infected with the indicated Salmonella strains bacteria live in the vesicle or target membranes SNAREs. Never-Ending Source of Surprises: from Natural Born Killers to Negotiators Health and does salmonella typhi produce toxins Services ( ). Authors resubmitted a revised version of the CI-M6PR sorting receptor allowed us to narrow set... ( Manders overlap coefficient ) represent the degree of co-localization between CI-M6PR and S. Typhi Paratyphi... Mutant prevented the efficient recruitment of CI-M6PR recruitment intracellular compartment these findings reveal how vesicle trafficking pathways are! The SCV, particularly at later times after infection 2 hr at 4C ( https: //imagej.nih.gov/.! Have found the recruitment of CI-M6PR recruitment to the SCV to the extracellular space host cells identified the...
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