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PubMedDate not supplied

Trypanosoma cruzi infection in Leontopithecus rosalia at the Reserva Biológica de Poco das Antas, Rio de Janeiro, Brazil.

Wild golden lion tamarins (Leontopithecus rosalia) - endangered primates that are native to the Brazilian Atlantic coastal forest - were surveyed for the presence of Trypanosoma cruzi with the use of Giemsa-stained blood smears, hemocultures and an indirect immunofluorescence assay (IFAT). Positive IFAT with titers ranging from 1:20 to 1:1280 were observed in 52% of the 118 wild tamarins examined and the parasite was isolated from 38 tamarins. No patent parasitemia was observed among the tamarins from which T. cruzi was isolated. Serum conversion and positive hemoculture was observed for three animals that had yielded negative results some months earlier, which indicates that T. cruzi is actively transmitted among tamarins. In contrast to observations with other sylvatic isolates, those from the tamarins were significantly more virulent and most of them produced mortality in experimentally infected Swiss mice. Some variation in the kDNA restriction profiles among the isolates was observed. Electrophoresis with GPI, G6PDH, IDH, MDH and ME enzymes showed a Z2 profile.

Animals↗

PubMed2006

[Changes of trace element content in MARC-145 cells before and after infection with virulent and attenuated strains of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)].

The influence of virulent and attenuated strains of Porcine Reproductive and Respiratory Syndrome Virus with defined genomic differences on trace element profile of MARC-145 cells was investigated to elucidate the process of infection in vitro. The concentrations of seven trace elements (Al, Cr, Mn, Ni, Fe, Cu, Zn) in infected and non-infected cells were determined. Although viral replication was similar in all cases, there were distinct features of difference in the trace element profiles (changes of concentrations of Ni, Mn, Fe) in infected cells. In particular, cells infected with the attenuated strain of PRRSV (NADC8-251) contained very low level of Ni, compared with its pathogenic counterpart NADC8-252K. The infection with the Lelystad strain also led to a moderately high level of this trace element.

Animals↗

PubMed2026

Comparative genomic analysis of Streptococcus parasuis and Streptococcus suis reveals mobile element-associated enrichment of antimicrobial resistance and lack of detectable same-MGE colocalization with virulence-associated genes within stable species boundaries.

Streptococcus suis is a major porcine pathogen and a zoonotic agent that causes meningitis and septicemia in humans. Streptococcus parasuis, a recently recognized close relative, remains poorly characterized with regard to its clinical significance and genomic features. In this study, we generated a single-contig closed genome assembly with genome-wide DNA methylation profiles for S. parasuis strain A1, isolated from a diseased pig in Xinjiang, China, and complemented in silico genomic predictions with isolate-level experimental validation of antimicrobial resistance (AMR) genotypes, virulence genotypes, and phenotypic susceptibility for this reference strain. Using this high-quality genome as a reference anchor, we performed comparative genomic analyses across 195 streptococcal genomes, comprising 15 S. parasuis and 180 S. suis strains, to distinguish genome-level co-occurrence of resistance and virulence determinants from their physical colocalization on the same mobile genetic element (MGE).Species boundaries remained clearly delineated at the genomic level, with a median interspecies average nucleotide identity (ANI) of approximately 86.0%, compared with intraspecies ANI medians of 97.5% for S. parasuis and 96.2% for S. suis. Pangenome analysis identified 12,693 gene clusters, of which 1086 were core clusters, and functional annotation revealed significant differences in accessory gene repertoires between the two species. Within this stable genomic framework, S. parasuis genomes carried a higher AMR gene burden; strain A1 harbored 10 AMR genes, multiple virulence-associated genes, three genomic islands, and eight prophage regions. For strain A1, PCR validation confirmed six AMR genes and six virulence genes, and disk diffusion testing demonstrated a multidrug-resistant phenotype consistent with the genotypic profile.Among 235 predicted mobile elements, 19 harbored AMR genes and seven carried Virulence Factor Database (VFDB) homologs, but none carried both categories simultaneously. This finding reflects a lack of detectable same-MGE colocalization under the applied annotation and assembly framework; it should not be interpreted as evidence of biological physical decoupling. Under a random-placement model, the expected number of co-carrying regions was only 0.57, and the probability of observing zero co-carrying regions was P = 0.55. This negative result should be interpreted with caution, given the limited number of cargo-bearing regions and the predominantly draft status of most genomes. Furthermore, the A1 genome contained multiple restriction-modification systems, showed depletion of several methylation motif families in mobile regions, and had limited CRISPR spacer matching evidence, suggesting prior exposure to the relevant sequence space. None of the genomes met our predefined criteria for whole-genome convergence.Collectively, our results support a model in which S. parasuis accumulates AMR-related genes in a modular fashion via mobile elements within stable species boundaries, with no detectable same-MGE colocalization of AMR and virulence determinants under our analytical pipeline. These findings imply that AMR surveillance strategies for this species should prioritize tracking mobile genetic elements rather than inferring wholesale genomic convergence toward S. suis.

Streptococcus suis↗

PubMed2001

Identification of a novel two-component regulatory system that acts in global regulation of virulence factors of Staphylococcus aureus.

We have previously demonstrated that the presence of oxygen is necessary for the production of toxic shock syndrome toxin 1 (TSST-1) by Staphylococcus aureus in vitro. To investigate the mechanism by which oxygen might regulate toxin production, we identified homologs in S. aureus of the Bacillus subtilis resDE genes. The two-component regulatory system encoded by resDE, ResD-ResE, has been implicated in the global regulation of aerobic and anaerobic respiratory metabolism in B. subtilis. We have designated the S. aureus homologs srrAB (staphylococcal respiratory response). The effects of srrAB expression on expression of RNAIII (the effector molecule of the agr locus) and on production of TSST-1 (an exotoxin) and protein A (a surface-associated virulence factor) were investigated. Expression of RNAIII was inversely related to expression of srrAB. Disruption of srrB resulted in increased levels of RNAIII, while expression of srrAB in trans on a multicopy plasmid resulted in repression of RNAIII transcription, particularly in microaerobic conditions. Disruption of srrB resulted in decreased production of TSST-1 under microaerobic conditions and, to a lesser extent, under aerobic conditions as well. Overexpression of srrAB resulted in nearly complete repression of TSST-1 production in both microaerobic and aerobic conditions. Protein A production by the srrB mutant was upregulated in microaerobic conditions and decreased in aerobic conditions. Protein A production was restored to nearly wild-type levels by complementation of srrAB into the null mutant. These results indicate that the putative two-component system encoded by srrAB, SrrA-SrrB, acts in the global regulation of staphylococcal virulence factors, and may repress virulence factors under low-oxygen conditions. Furthermore, srrAB may provide a mechanistic link between respiratory metabolism, environmental signals, and regulation of virulence factors in S. aureus.

Aerobiosis↗

PubMed2006

Quantitative analysis of a virulent bacteriophage transcription strategy.

An increasingly large number of bacteriophage genomes are being sequenced each year. What is an efficient experimental and computational procedure to analyze transcription strategies of newly sequenced novel bacteriophages? We address this issue using an example of bacteriophage Xp10, which infects rice pathogen Xanthomonas oryzae. This phage is particularly challenging for analysis, since part of its genome is jointly transcribed by two (host and viral) RNA polymerases. To understand the roles played by the two RNA polymerases, we developed a novel method of data analysis which combines quantitative analysis of Xp10 global gene expression data and kinetic modeling of the infection process. To generalize our approach, we discuss how our method can be applied to other systems and argue that genomic array experiments combined with the methods of data analysis that we present provide an efficient way to analyze gene expression strategies of novel bacteriophages.

Bacteriophages↗

PubMed2002

Genetic approaches to studying virulence and pathogenesis in Toxoplasma gondii.

Toxoplasma gondii is a common protozoan parasite that causes disease in immunocompromised humans. Equipped with a wide array of experimental tools, T. gondii has rapidly developed as a model parasite for genetic studies. The population structure of T. gondii is highly clonal, consisting of three distinct lineages that differ dramatically in virulence. Acute virulence is probably mediated by the genetic differences that distinguish strain types. We have utilized a combination of genetic approaches to investigate the acute virulence of toxoplasmosis using the mouse model. These studies reveal the surprising finding that pathogenicity is due to the over-stimulation of normally protective immune responses. Classical genetic linkage mapping studies indicate that genes that mediate acute virulence are linked to chromosome VII in the parasite. To increase the resolution of genetic mapping studies, single-nucleotide polymorphisms are being developed based on an extensive database of expressed sequence tags (ESTs) from T. gondii. Separately, DNA microarray studies are being used to examine the expression of parasite and host genes during infection. Collectively, these approaches should improve current understanding of virulence and pathogenicity in toxoplasmosis.

Alleles↗

PubMed1997

Pseudorabies virus recombinants expressing functional virulence determinants gE and gI from bovine herpesvirus 1.1.

In the Alphaherpesvirinae subfamily, the gE and gI genes are conserved and encode membrane glycoproteins required for efficient pathogenesis (virulence). The molecular mechanism(s) responsible is not well understood, but the existence of similar phenotypes of gE and gI mutations in diverse Alphaherpesvirinae implies conservation of function(s). In this report, we describe construction of pseudorabies virus (PRV) recombinants that efficiently express the bovine herpesvirus 1 (BHV-1) membrane proteins gI and gE at the PRV gG locus. Each BHV-1 gene was cloned in a PRV mutant lacking both the PRV gI and gE coding sequences. All recombinant viruses expressed the BHV-1 proteins at levels similar to or greater than that observed after infection with parental BHV-1, and there were no observable differences in processing or ability to form gE-gI oligomers. The important observation resulting from this report is that the BHV-1 gE and gI proteins functioned together to complement the virulence defect of PRV lacking its own gE and gI genes in a rodent model, despite being derived from a highly restricted host range virus with a different pathogenic profile.

Animals↗

PubMedDate not supplied

Biological and molecular characterization of Newcastle disease virus (NDV) field isolates with comparisons to reference NDV strains.

Fifty-seven Newcastle disease virus (NDV) isolates from chickens, turkeys, a rhea, a parrot, and an anhinga were pathotyped and characterized by monoclonal antibody (mAb) inhibition profile, elution rate, and hemagglutinin thermostability. Nucleotide sequence analysis of portions of the fusion protein and matrix protein genes of the parrot isolate was done for comparison with prior sequence analysis of the anhinga isolate and NDV reference strains. Seven of the 43 chicken isolates were recovered from flocks in Canada. The remaining isolates, including 11 from turkeys, were isolated in the United States. All isolates except that of the anhinga were of low virulence by mean death time in embryos, intracerebral pathogenicity index, and/or intravenous pathogenicity index procedures and were classified as lentogens. The anhinga isolate was more virulent than the other strains and was pathotyped as a mesogen. However, nucleotide sequence analysis of the anhinga isolate had revealed a homology with the virulent cormorant isolates of 1992 rather than the classical U.S. mesogens characterized by the Roakin strain. Variability was evident among the lentogenic isolates. Two isolates from turkeys had mAb profiles that differed from B1 and La Sota reference and vaccine strains, and 38% (21/56) of the isolates had more thermostable hemagglutinins than those reference strains. There was no evidence that any of the isolates from poultry were more virulent than the lentogenic pathotype.

Animals↗

PubMed2004

Use of cDNA microarrays to analyze responses to pneumococcal virulence factors.

BACKGROUND & OBJECTIVES: The complex interactions that occur between host and pathogen during bacteraemia caused by Streptococcus pneumoniae are not well understood. Upon entering the blood stream the pneumococcus intiates responses through contact with naïve monocytes and macrophages resulting in an inflammatory response. To elucidate the role of microbial virulence factors in the host response to the pneumococcus, cDNA microarray analysis was used to identify genes in THP-1 cells, a human monocytic cell line, that are responsive to pneumococcal virulence factors. METHODS: S. pneumoniae D39, a serotype 2 pneumococcus, and PLN an isogenic mutant of D39 that does not express pneumolysin were used. Gene expression profiles elicited by both wild-type and mutant were compared with that of THP-1 cells not exposed to pneumococci. Results obtained from microarray analysis were confirmed and further characterized using reverse transcriptase (RT)-PCR, real-time RT-PCR, and ELISA. RESULTS: Genes in THP-1 cells that were responsive to the pneumococcus independent of the presence of the specific virulence factor, pneumolysin, were identified. THP-1 cell genes that were differentially expressed independent of pneumolysin included the ones involved in cell-to-cell signaling and antipathogen responses. Those that were responsive to pneumolysin included genes encoding adhesion molecules, chemokines, cytokine receptors, and cell cycle and apoptosis proteins. INTERPRETATION & CONCLUSION: The global transcriptional response of naïve monocytes to contact with the pneumococcus was characterized and the utility of cDNA microarray analysis in elucidating the role of specific factors in host-pathogen interactions were demonstrated.

Cell Line↗

PubMed1995

Comparison of outer membrane protein and lipopolysaccharide profiles of enterotoxigenic Escherichia coli strains isolated in São Paulo, Brazil.

The outer membrane protein (OMP) and lipopolysaccharide (LPS) patterns of 12 strains of serogroups of enterotoxigenic E. coli frequently isolated in São Paulo city were determined by fractionation techniques and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Five O6, three O78 and four O128 serogroup isolates of different serotypes (flagellar antigens) and virulence factors (toxins and colonization factor antigens) showed a high degree of variability in their OMP pattern and at least nine groups could be identified. The analysis of LPS patterns by SDS-PAGE showed a homogeneous profile for the O6 strains and some minor differences for the O128 and O78 strains. The present data indicate that analysis of OMP and LPS by SDS-PAGE may further improve the discriminating ability of extensively used serological techniques or the detection of virulence factors and could be a useful tool in epidemiological studies of enterotoxigenic E. coli (ETEC) strains from this area.

Bacterial Outer Membrane Proteins↗

PubMed2005

Plasmodium chabaudi adami: use of the B-cell-deficient mouse to define possible mechanisms modulating parasitemia of chronic malaria.

Our previous observation that B-cell-deficient JH-/- mice utilize T cell-dependent immunity to suppress acute Plasmodium chabaudi adami-induced malaria but then develop chronic low-level parasitemia prompted this study of control mechanisms for chronic parasitemia. When we infected JH-/- mice with blood-stage parasites, chronic parasitemia exacerbated after the 6th month and persisted for up to 17 months. This exacerbation of parasitemia could not be attributed to host aging because the time-course of acute infection in naïve aged mice was nearly identical to that seen in young mice. Nor could exacerbated parasitemia be attributed to mutation in the parasite genome resulting in increased virulence; when subinoculated into naïve JH-/- mice, parasites from chronically infected JH-/- mice with exacerbated parasitemia produced acute stage parasitemia profiles in most recipients comparable to those seen in JH-/- mice upon infection with the original stabilate material. Of the pro-inflammatory cytokines measured, including IFNgamma, TNFalpha, IL-12p70, and MCP-1beta, none were significantly different in the sera of mice with exacerbated parasitemia compared to uninfected controls. Levels of IL-6 were significantly (P=0.002) less in the sera of mice with exacerbated parasitemia. Serum levels of the anti-inflammatory cytokine, TGFbeta, were significantly depressed in chronically infected JH-/- mice compared to uninfected controls. In contrast, IL-10 levels were markedly increased. These findings suggest that the cytokine balance may be disturbed during chronic malaria, thereby impacting on mechanisms that modulate levels of parasitemia.

Aging↗

PubMed2006

Characterization, distribution, and expression of novel genes among eight clinical isolates of Streptococcus pneumoniae.

Eight low-passage-number Streptococcus pneumoniae clinical isolates, each of a different serotype and a different multilocus sequence type, were obtained from pediatric participants in a pneumococcal vaccine trial. Comparative genomic analyses were performed with these strains and two S. pneumoniae reference strains. Individual genomic libraries were constructed for each of the eight clinical isolates, with an average insert size of approximately 1 kb. A total of 73,728 clones were picked for arraying, providing more than four times genomic coverage per strain. A subset of 4,793 clones were sequenced, for which homology searches revealed that 750 (15.6%) of the sequences were unique with respect to the TIGR4 reference genome and 263 (5.5%) clones were unrelated to any available streptococcal sequence. Hypothetical translations of the open reading frames identified within these novel sequences showed homologies to a variety of proteins, including bacterial virulence factors not previously identified in S. pneumoniae. The distribution and expression patterns of 58 of these novel sequences among the eight clinical isolates were analyzed by PCR- and reverse transcriptase PCR-based analyses, respectively. These unique sequences were nonuniformly distributed among the eight isolates, and transcription of these genes in planktonic cultures was detected in 81% (172/212) of their genic occurrences. All 58 novel sequences were transcribed in one or more of the clinical strains, suggesting that they all correspond to functional genes. Sixty-five percent (38/58) of these sequences were found in 50% or less of the clinical strains, indicating a significant degree of genomic plasticity among natural isolates.

Bacteriocins↗

PubMed2007

Proteomics analysis of the Francisella tularensis LVS response to iron restriction: induction of the F. tularensis pathogenicity island proteins IglABC.

Francisella tularensis is a highly virulent, facultative intracellular pathogen that causes tularemia in humans and animals. Although it is one of the most infectious bacterial pathogens, little is known about its virulence mechanisms. In this study, the response of F. tularensis live vaccine strain to iron depletion, which simulates the environment within the host, was investigated. In order to detect alterations in protein synthesis, metabolic labeling, followed by 2D-PAGE analysis was used. Globally, 141 protein spots were detected whose levels were significantly altered in the iron-restricted medium. About 65% of the spots were successfully identified using mass spectrometric approaches. Importantly, among the proteins produced at an increased level during iron-limited growth, three proteins were found encoded by the igl operon, located in the F. tularensis pathogenicity island I (FPI). Of these, the IglC and IglA proteins were previously reported to be necessary for full virulence of F. tularensis. These results, obtained at the proteome level, support and confirm recently published data showing that the igl operon genes are transcribed in response to iron limitation.

Bacterial Proteins↗

PubMed2004

Fitness of Toxoplasma gondii is not related to DHFR single-nucleotide polymorphism during congenital toxoplasmosis.

Factors that regulate the pathogenesis of Toxoplasma gondii in humans are poorly understood. When acquired during pregnancy, toxoplasmosis can be disastrous, leading to fetal loss or conversely to subclinical disease. In congenitally infected infants, evolution is highly unpredictable. Genotype based virulence patterns have been described in mice, but in humans this classification does not correlate with the gravity of the disease. Mutations on DHFR-TS loci have recently been reported to confer T. gondii fitness cost. In this study, we investigated the relationship between the virulence of the parasite, as measured by clinical outcome in the fetus or newborn, fitness, as measured by parasitic load in amniotic fluid, and allelic polymorphism in DHFR. Six cases of severe congenital toxoplasmosis and 23 cases of mild congenital infections were included in the study. Quantitative PCR was performed to evaluate total T. gondii DNA load in amniotic fluid and detection of mutations was carried out with a LightCycler using hybridisation probes. Parasitic load was significantly higher in severe infections than in mild diseases. Among isolates from severe or non-severe cases of congenital toxoplasmosis, no polymorphism could be detected at loci 36, 83 or 245 of the DHFR gene. The virulent RH strain presented the same melting temperature as the non-virulent PRU strain for codons 36, 83 and 245. Only mutated clones, M2M3 and M2M4 with allelic replacement at these positions, displayed different profiles allowing a clear distinction between wild and mutant types. We concluded that the DHFR gene mutations we investigated do not regulate T. gondii fitness in humans.

Animals↗

PubMed2006

DNA microarray analyses reveal a post-irradiation differential time-dependent gene expression profile in yeast cells exposed to X-rays and gamma-rays.

Ionizing radiation (IR) is the most enigmatic of genotoxic stress inducers in our environment that has been around from the eons of time. IR is generally considered harmful, and has been the subject of numerous studies, mostly looking at the DNA damaging effects in cells and the repair mechanisms therein. Moreover, few studies have focused on large-scale identification of cellular responses to IR, and to this end, we describe here an initial study on the transcriptional responses of the unicellular genome model, yeast (Saccharomyces cerevisiae strain S288C), by cDNA microarray. The effect of two different IR, X-rays, and gamma (gamma)-rays, was investigated by irradiating the yeast cells cultured in YPD medium with 50 Gy doses of X- and gamma-rays, followed by resuspension of the cells in YPD for time-course experiments. The samples were collected for microarray analysis at 20, 40, and 80 min after irradiation. Microarray analysis revealed a time-course transcriptional profile of changed gene expressions. Up-regulated genes belonged to the functional categories mainly related to cell cycle and DNA processing, cell rescue defense and virulence, protein and cell fate, and metabolism (X- and gamma-rays). Similarly, for X- and gamma-rays, the down-regulated genes belonged to mostly transcription and protein synthesis, cell cycle and DNA processing, control of cellular organization, cell fate, and C-compound and carbohydrate metabolism categories, respectively. This study provides for the first time a snapshot of the genome-wide mRNA expression profiles in X- and gamma-ray post-irradiated yeast cells and comparatively interprets/discusses the changed gene functional categories as effects of these two radiations vis-à-vis their energy levels.

Down-Regulation↗

PubMed1996

Genome organization of the Kresse strain of porcine parvovirus: identification of the allotropic determinant and comparison with those of NADL-2 and field isolates.

The Kresse strain of porcine parvovirus (PPV) was cloned into pUC19, and independent infectious clones were sequenced. The PPV Kresse and NADL-2 strains, which have different pathogenicities, shared an identical genomic organization and a high degree of sequence identity. Partial genomes (1.5 or 1.6 kb) of 15 field isolates were also amplified by PCR in regions with significant sequence differences between the laboratory strains. Five amino acid differences were consistently present within the VP1/VP2 coding region of the Kresse strain and virulent field isolates. A number of inconsistent point mutations were also found throughout the genomes of field isolates. In addition, among those with the vaccine amino acid profile, all but one isolate (IAF-3) contained a 127-bp noncoding direct repeat downstream of the capsid protein gene. The one exception was also the only vaccine-type PPV obtained from a mummified fetus. In order to identify genetic elements responsible for the distinct tropism (and possibly the pathology) of the Kresse strain, in vitro cell systems which differentiated the virulent from the vaccinal strains were established. Subsequently, chimeric infectious clones of the Kresse and NADL-2 strains were used to identify the allotropic determinant located in the VP1/VP2 region. The transfer of the BglII fragment of the Kresse genome, containing three amino acid differences, into the NADL-2 background, or the opposite construct, caused the phenotype of the target genome to revert to that of the parent strain of the BglII fragment. Prediction of the localization of amino acid differences on the basis of canine parvovirus capsid structure indicates that each is located on or near the outer surface of the virion. In particular, the position of one mutation (S-436-->P) maps by analogy to the threefold spike, the most accessible region of the capsid.

Amino Acid Sequence↗

PubMed2006

Transcription of virulence factors in Staphylococcus aureus small-colony variants isolated from cystic fibrosis patients is influenced by SigB.

Staphylococcus aureus small-colony variants (SCVs) are believed to account in part for the persistence of S. aureus during chronic infections. Little is understood about the gene expression profile that may explain the phenotype and distinguish SCVs from prototype S. aureus strains. In this study, DNA array transcriptional profiles of clinical SCVs isolated from the airways of cystic fibrosis patients were obtained and compared to those obtained from a laboratory-derived SCV strain (i.e., a respiratory-deficient hemB mutant) and prototype S. aureus strains. The genes commonly up-regulated in both hemB and clinical SCVs were found to be implicated in fermentation and glycolysis pathways. The well-known virulence regulator agr was not activated in SCVs, and such strains had low levels of alpha-toxin (hla) gene expression. Clinical SCVs also had a transcriptional signature of their own. Of striking interest is that many genes, most of them under the positive control of the alternate sigma factor SigB, were specifically up-regulated and differed in that way from that seen in prototype S. aureus and the hemB mutant. Since SigB influences up-regulation of adhesin type genes while indirectly down-regulating exoproteins and toxins, we evaluated the internalization and persistence of SCVs in mammalian cells. Results showed that clinical SCVs persisted much more efficiently in cells than the hemB and prototype strains and that a sigB mutant was a poor persister. Thus, it appears that the agr locus plays a minor role in the regulation of the virulon of SCVs, unlike SigB, which may have a key role in intracellular persistence.

Animals↗

PubMed2005

Trafficking of STEVOR to the Maurer's clefts in Plasmodium falciparum-infected erythrocytes.

The human malarial parasite Plasmodium falciparum exports proteins to destinations within its host erythrocyte, including cytosol, surface and membranous profiles of parasite origin termed Maurer's clefts. Although several of these exported proteins are determinants of pathology and virulence, the mechanisms and trafficking signals underpinning protein export are largely uncharacterized-particularly for exported transmembrane proteins. Here, we have investigated the signals mediating trafficking of STEVOR, a family of transmembrane proteins located at the Maurer's clefts and believed to play a role in antigenic variation. Our data show that, apart from a signal sequence, a minimum of two addition signals are required. This includes a host cell targeting signal for export to the host erythrocyte and a transmembrane domain for final sorting to Maurer's clefts. Biochemical studies indicate that STEVOR traverses the secretory pathway as an integral membrane protein. Our data suggest general principles for transport of transmembrane proteins to the Maurer's clefts and provide new insights into protein sorting and trafficking processes in P. falciparum.

Amino Acid Sequence↗