Complementary roles of EPS, T3SS and Expansin for virulence of Erwinia tracheiphila, the causative agent of cucurbit wilt.

Erwinia tracheiphila (Smith) is a recently emerged plant pathogen that causes severe economic losses in cucurbit crops in temperate Eastern North America. E. tracheiphila is xylem restricted, and virulence is thought to be related to Exopolysaccharides (EPS) and biofilm formation, which occlude the passage of sap in xylem vessels and causes systemic wilt. However, the role of EPS and biofilm formation, and their contribution to disease in relation to other virulence loci are unknown. Here, we use deletion mutants to explore the roles of EPS, Hrp Type III secretion system (Hrp T3SS) and Expansin in plant colonization and virulence. Then, we quantify the expression of the genes encoding these factors during infection. Our results show that Exopolysaccharides are essential for E. tracheiphila survival in host plants, while Hrp T3SS and Expansin are dispensable for survival but needed for systemic wilt symptom development. EPS and Hrp T3SS display contrasting expression patterns in the plant, reflecting their relevance in different stages of the infection. Finally, we show that expression of the eps and hrpT3SS operons is downregulated in mildly increased temperatures, suggesting a link between expression of these virulence factors and geographic restriction of E. tracheiphila to temperate regions. Our work highlights how E. tracheiphila virulence is a complex trait where several loci are coordinated during infection. These results further shed light into the relationship between virulence factors and the ecology of this pathosystem, which will be essential for developing sustainable management strategies for this emerging pathogen.

Herbarium specimens reveal herbivory patterns across the genus Cucurbita.

PREMISE: Quantifying how closely related plant species differ in susceptibility to insect herbivory is important for understanding the variation in evolutionary pressures on plant functional traits. However, empirically measuring in situ variation in herbivory spanning the geographic range of a plant-insect complex is logistically difficult. Recently, new methods have been developed using herbarium specimens to investigate patterns in plant-insect symbioses across large geographic scales. Such investigations provide insights into how accelerated anthropogenic changes may impact plant-insect interactions that are of ecological or agricultural importance. METHODS: Here, we analyze 274 pressed herbarium samples to investigate variation in herbivory damage in 13 different species of the economically important plant genus Cucurbita (Cucurbitaceae). This collection is composed of specimens of wild, undomesticated Cucurbita that were collected from across their native range, and Cucurbita cultivars collected from both within their native range and from locations where they have been introduced for agriculture in temperate North America. RESULTS: Herbivory is common on individuals of all Cucurbita species collected throughout their geographic ranges. However, estimates of herbivory varied considerably among individuals, with mesophytic species accruing more insect damage than xerophytic species, and wild specimens having more herbivory than specimens collected from human-managed habitats. CONCLUSIONS: Our study suggests that long-term evolutionary changes in habitat from xeric to mesic climates and wild to human-managed habitats may mediate the levels of herbivory pressure from coevolved herbivores. Future investigations into the potential factors that contribute to herbivory may inform the management of domesticated crop plants and their insect herbivores.

The diversity and function of sourdough starter microbiomes.

Humans have relied on sourdough starter microbial communities to make leavened bread for thousands of years, but only a small fraction of global sourdough biodiversity has been characterized. Working with a community-scientist network of bread bakers, we determined the microbial diversity of 500 sourdough starters from four continents. In sharp contrast with widespread assumptions, we found little evidence for biogeographic patterns in starter communities. Strong co-occurrence patterns observed in situ and recreated in vitro demonstrate that microbial interactions shape sourdough community structure. Variation in dough rise rates and aromas were largely explained by acetic acid bacteria, a mostly overlooked group of sourdough microbes. Our study reveals the extent of microbial diversity in an ancient fermented food across diverse cultural and geographic backgrounds.

Sourdough bread is an ancient fermented food that has sustained humans around the world for thousands of years. It is made from a sourdough 'starter culture' which is maintained, portioned, and shared among bread bakers around the world. The starter culture contains a community of microbes made up of yeasts and bacteria, which ferment the carbohydrates in flour and produce the carbon dioxide gas that makes the bread dough rise before baking. The different acids and enzymes produced by the microbial culture affect the bread's flavor, texture and shelf life. However, for such a dependable staple, sourdough bread cultures and the mixture of microbes they contain have scarcely been characterized. Previous studies have looked at the composition of starter cultures from regions within Europe. But there has never been a comprehensive study of how the microbial diversity of sourdough starters varies across and between continents. To investigate this, Landis, Oliverio et al. used genetic sequencing to characterize the microbial communities of sourdough starters from the homes of 500 bread bakers in North America, Europe and Australasia. Bread makers often think their bread's unique qualities are due to the local environment of where the sourdough starter was made. However, Landis, Oliverio et al. found that geographical location did not correlate with the diversity of the starter cultures studied. The data revealed that a group of microbes called acetic acid bacteria, which had been overlooked in past research, were relatively common in starter cultures. Moreover, starters with a greater abundance of this group of bacteria produced bread with a strong vinegar aroma and caused dough to rise at a slower rate. This research demonstrates which species of bacteria and yeast are most commonly found in sourdough starters, and suggests geographical location has little influence on the microbial diversity of these cultures. Instead, the diversity of microbes likely depends more on how the starter culture was made and how it is maintained over time.

A horizontally acquired expansin gene increases virulence of the emerging plant pathogen Erwinia tracheiphila.

Erwinia tracheiphila is a bacterial plant pathogen that causes a fatal wilt infection in some cucurbit crop plants. Wilt symptoms are thought to be caused by systemic bacterial colonization through xylem that impedes sap flow. However, the genetic determinants of within-plant movement are unknown for this pathogen species. Here, we find that E. tracheiphila has horizontally acquired an operon with a microbial expansin (exlx) gene adjacent to a glycoside hydrolase family 5 (gh5) gene. Plant inoculation experiments with deletion mutants in the individual genes (Δexlx and Δgh5) and the full operon (Δexlx-gh5) resulted in decreased severity of wilt symptoms, decreased mortality rate, and impaired systemic colonization compared to the Wt strain. Co-inoculation experiments with Wt and Δexlx-gh5 rescued the movement defect of the mutant strain, suggesting that expansin and GH5 function extracellularly. Together, these results show that expansin-GH5 contributes to systemic movement through xylem, leading to rapid wilt symptom development and higher rates of plant death. The presence of expansin genes in diverse species of bacterial and fungal wilt-inducing pathogens suggests that microbial expansin proteins may be an under-appreciated virulence factor for many pathogen species.

Global cellulose biomass, horizontal gene transfers and domain fusions drive microbial expansin evolution.

Plants must rearrange the network of complex carbohydrates in their cell walls during normal growth and development. To accomplish this, all plants depend on proteins called expansins that nonenzymatically loosen noncovalent bonding between cellulose microfibrils. Surprisingly, expansin genes have more recently been found in some bacteria and microbial eukaryotes, where their biological functions are largely unknown. Here, we reconstruct a comprehensive phylogeny of microbial expansin genes. We find these genes in all eukaryotic microorganisms that have structural cell wall cellulose, suggesting expansins evolved in ancient marine microorganisms long before the evolution of land plants. We also find expansins in an unexpectedly high diversity of bacteria and fungi that do not have cellulosic cell walls. These bacteria and fungi inhabit varied ecological contexts, mirroring the diversity of terrestrial and aquatic niches where plant and/or algal cellulosic cell walls are present. The microbial expansin phylogeny shows evidence of multiple horizontal gene transfer events within and between bacterial and eukaryotic microbial lineages, which may in part underlie their unusually broad phylogenetic distribution. Overall, expansins are unexpectedly widespread in bacteria and eukaryotes, and the contribution of these genes to microbial ecological interactions with plants and algae has probbaly been underappreciated.

Draft Genome Sequence of an Erwinia tracheiphila Isolate from an Infected Muskmelon (Cucumis melo).

Erwinia tracheiphila is a bacterial plant pathogen emerging in eastern North America. To aid in understanding genetic variation within E. tracheiphila, here we sequence the first reference genome of an infected muskmelon (Cucumis melo). The genome assembles into a single chromosomal contig, three plasmid contigs, and one bacteriophage contig.

Enrichment of Verrucomicrobia, Actinobacteria and Burkholderiales drives selection of bacterial community from soil by maize roots in a traditional milpa agroecosystem.

Milpas are rain-fed agroecosystems involving domesticated, semi-domesticated and tolerated plant species that combine maize with a large variety of other crop, tree or shrub species. Milpas are low input and low-tillage, yet highly productive agroecosystems, which have been maintained over millennia in indigenous communities in Mexico and other countries in Central America. Thus, milpas may retain ancient plant-microorganisms interactions, which could have been lost in modern high-tillage monocultures with large agrochemical input. In this work, we performed high-throughput 16S ribosomal DNA sequencing of soil adjacent to maize roots and bulk soil sampled at 30 cm from the base of the plants. We found that the bacterial communities of maize root soil had a lower alpha diversity, suggesting selection of microorganisms by maize-roots from the bulk-soil community. Beta diversity analysis confirmed that these environments harbor two distinct microbial communities; differences were driven by members of phyla Verrucomicrobia and Actinobacteria, as well as the order Burkholderiales (Betaproteobacteria), all of which had higher relative abundance in soil adjacent to the roots. Numerous studies have shown the influence of maize plants on bacterial communities found in soil attached tightly to the roots; here we further show that the influence of maize roots at milpas on bacterial communities is detectable even in plant-free soil collected nearby. We propose that members of Verrucomicrobia and other phyla found in the rhizosphere may establish beneficial plant-microbe interactions with maize roots in milpas, and propose to address their cultivation for future studies on ecology and potential use.

An Introduced Crop Plant Is Driving Diversification of the Virulent Bacterial Pathogen Erwinia tracheiphila.

Erwinia tracheiphila is the causal agent of bacterial wilt of cucurbits, an economically important phytopathogen affecting an economically important phytopathogen affecting few cultivated Cucurbitaceae few cultivated Cucurbitaceae host plant species in temperate eastern North America. However, essentially nothing is known about E. tracheiphila population structure or genetic diversity. To address this shortcoming, a representative collection of 88 E. tracheiphila isolates was gathered from throughout its geographic range, and their genomes were sequenced. Phylogenomic analysis revealed three genetic clusters with distinct hrpT3SS virulence gene repertoires, host plant association patterns, and geographic distributions. Low genetic heterogeneity within each cluster suggests a recent population bottleneck followed by population expansion. We showed that in the field and greenhouse, cucumber (Cucumis sativus), which was introduced to North America by early Spanish conquistadors, is the most susceptible host plant species and the only species susceptible to isolates from all three lineages. The establishment of large agricultural populations of highly susceptible C. sativus in temperate eastern North America may have facilitated the original emergence of E. tracheiphila into cucurbit agroecosystems, and this introduced plant species may now be acting as a highly susceptible reservoir host. Our findings have broad implications for agricultural sustainability by drawing attention to how worldwide crop plant movement, agricultural intensification, and locally unique environments may affect the emergence, evolution, and epidemic persistence of virulent microbial pathogens.IMPORTANCEErwinia tracheiphila is a virulent phytopathogen that infects two genera of cucurbit crop plants, Cucurbita spp. (pumpkin and squash) and Cucumis spp. (muskmelon and cucumber). One of the unusual ecological traits of this pathogen is that it is limited to temperate eastern North America. Here, we complete the first large-scale sequencing of an E. tracheiphila isolate collection. From phylogenomic, comparative genomic, and empirical analyses, we find that introduced Cucumis spp. crop plants are driving the diversification of E. tracheiphila into multiple lineages. Together, the results from this study show that locally unique biotic (plant population) and abiotic (climate) conditions can drive the evolutionary trajectories of locally endemic pathogens in unexpected ways.

Evolutionary Determinants of Host and Vector Manipulation by Plant Viruses.

Plant viruses possess adaptations for facilitating acquisition, retention, and inoculation by vectors. Until recently, it was hypothesized that these adaptations are limited to virus proteins that enable virions to bind to vector mouthparts or invade their internal tissues. However, increasing evidence suggests that viruses can also manipulate host plant phenotypes and vector behaviors in ways that enhance their own transmission. Manipulation of vector-host interactions occurs through virus effects on host cues that mediate vector orientation, feeding, and dispersal behaviors, and thereby, the probability of virus transmission. Effects on host phenotypes vary by pathosystem but show a remarkable degree of convergence among unrelated viruses whose transmission is favored by the same vector behaviors. Convergence based on transmission mechanism, rather than phylogeny, supports the hypothesis that virus effects are adaptive and not just by-products of infection. Based on this, it has been proposed that viruses manipulate hosts through multifunctional proteins that facilitate exploitation of host resources and elicitation of specific changes in host phenotypes. But this proposition is rarely discussed in the context of the numerous constraints on virus evolution imposed by molecular and environmental factors, which figure prominently in research on virus-host interactions not dealing with host manipulation. To explore the implications of this oversight, we synthesized available literature to identify patterns in virus effects among pathogens with shared transmission mechanisms and discussed the results of this synthesis in the context of molecular and environmental constraints on virus evolution, limitations of existing studies, and prospects for future research.

Complete Genome Sequence of EtG, the First Phage Sequenced from Erwinia tracheiphila.

Erwinia tracheiphila is the causal agent of bacterial wilt of cucurbits. Here, we report the genome sequence of the temperate phage EtG, which was isolated from an E. tracheiphila-infected cucumber plant. Phage EtG has a linear 30,413-bp double-stranded DNA genome with cohesive ends and 45 predicted open reading frames.

Rhizosphere-associated Pseudomonas induce systemic resistance to herbivores at the cost of susceptibility to bacterial pathogens.

Plant-associated soil microbes are important mediators of plant defence responses to diverse above-ground pathogen and insect challengers. For example, closely related strains of beneficial rhizosphere Pseudomonas spp. can induce systemic resistance (ISR), systemic susceptibility (ISS) or neither against the bacterial foliar pathogen Pseudomonas syringae pv. tomato DC3000 (Pto DC3000). Using a model system composed of root-associated Pseudomonas spp. strains, the foliar pathogen Pto DC3000 and the herbivore Trichoplusia ni (cabbage looper), we found that rhizosphere-associated Pseudomonas spp. that induce either ISS and ISR against Pto DC3000 all increased resistance to herbivory by T. ni. We found that resistance to T. ni and resistance to Pto DC3000 are quantitative metrics of the jasmonic acid (JA)/salicylic acid (SA) trade-off and distinct strains of rhizosphere-associated Pseudomonas spp. have distinct effects on the JA/SA trade-off. Using genetic analysis and transcriptional profiling, we provide evidence that treatment of Arabidopsis with Pseudomonas sp. CH267, which induces ISS against bacterial pathogens, tips the JA/SA trade-off towards JA-dependent defences against herbivores at the cost of a subset of SA-mediated defences against bacterial pathogens. In contrast, treatment of Arabidopsis with the ISR strain Pseudomonas sp. WCS417 disrupts JA/SA antagonism and simultaneously primes plants for both JA- and SA-mediated defences. Our findings show that ISS against the bacterial foliar pathogens triggered by Pseudomonas sp. CH267, which is a seemingly deleterious phenotype, may in fact be an adaptive consequence of increased resistance to herbivory. Our work shows that pleiotropic effects of microbiome modulation of plant defences are important to consider when using microbes to modify plant traits in agriculture.

Horizontal Gene Acquisitions, Mobile Element Proliferation, and Genome Decay in the Host-Restricted Plant Pathogen Erwinia Tracheiphila.

Modern industrial agriculture depends on high-density cultivation of genetically similar crop plants, creating favorable conditions for the emergence of novel pathogens with increased fitness in managed compared with ecologically intact settings. Here, we present the genome sequence of six strains of the cucurbit bacterial wilt pathogen Erwinia tracheiphila (Enterobacteriaceae) isolated from infected squash plants in New York, Pennsylvania, Kentucky, and Michigan. These genomes exhibit a high proportion of recent horizontal gene acquisitions, invasion and remarkable amplification of mobile genetic elements, and pseudogenization of approximately 20% of the coding sequences. These genome attributes indicate that E. tracheiphila recently emerged as a host-restricted pathogen. Furthermore, chromosomal rearrangements associated with phage and transposable element proliferation contribute to substantial differences in gene content and genetic architecture between the six E. tracheiphila strains and other Erwinia species. Together, these data lead us to hypothesize that E. tracheiphila has undergone recent evolution through both genome decay (pseudogenization) and genome expansion (horizontal gene transfer and mobile element amplification). Despite evidence of dramatic genomic changes, the six strains are genetically monomorphic, suggesting a recent population bottleneck and emergence into E. tracheiphila's current ecological niche.

Draft Genome Sequence of Erwinia tracheiphila, an Economically Important Bacterial Pathogen of Cucurbits.

Erwinia tracheiphila is one of the most economically important pathogens of cucumbers, melons, squashes, pumpkins, and gourds in the northeastern and midwestern United States, yet its molecular pathology remains uninvestigated. Here, we report the first draft genome sequence of an E. tracheiphila strain isolated from an infected wild gourd (Cucurbita pepo subsp. texana) plant. The genome assembly consists of 7 contigs and includes a putative plasmid and at least 20 phage and prophage elements.

Bacterial Wilt of Cucurbits: Resurrecting a Classic Pathosystem.

Bacterial wilt threatens cucurbit crop production in the Midwestern and Northeastern United States. The pathogen, Erwinia tracheiphila, is a xylem-limited bacterium that affects most commercially important cucurbit species, including muskmelon, cucumber, and squash. Bacterial wilt is transmitted and overwintered by striped and spotted cucumber beetles. Since there are few commercially available resistant cultivars, disease management usually relies on use of insecticides to suppress vector populations. Although bacterial wilt was initially described more than 100 years ago, our knowledge of disease ecology and epidemiology advanced slowly for most of the 20th century. However, a recent wave of research has begun to fill in missing pieces of the bacterial wilt puzzle. This article-the first review of research toward understanding the cucurbit bacterial wilt pathosystem-recounts early findings and updates our understanding of the disease cycle, including pathogen and vector biology. We also highlight research areas that could lead to more efficient and ecologically based management of bacterial wilt.

Disease interactions in a shared host plant: effects of pre-existing viral infection on cucurbit plant defense responses and resistance to bacterial wilt disease.

Both biotic and abiotic stressors can elicit broad-spectrum plant resistance against subsequent pathogen challenges. However, we currently have little understanding of how such effects influence broader aspects of disease ecology and epidemiology in natural environments where plants interact with multiple antagonists simultaneously. In previous work, we have shown that healthy wild gourd plants (Cucurbita pepo ssp. texana) contract a fatal bacterial wilt infection (caused by Erwinia tracheiphila) at significantly higher rates than plants infected with Zucchini yellow mosaic virus (ZYMV). We recently reported evidence that this pattern is explained, at least in part, by reduced visitation of ZYMV-infected plants by the cucumber beetle vectors of E. tracheiphila. Here we examine whether ZYMV-infection may also directly elicit plant resistance to subsequent E. tracheiphila infection. In laboratory studies, we assayed the induction of key phytohormones (SA and JA) in single and mixed infections of these pathogens, as well as in response to the feeding of A. vittatum cucumber beetles on healthy and infected plants. We also tracked the incidence and progression of wilt disease symptoms in plants with prior ZYMV infections. Our results indicate that ZYMV-infection slightly delays the progression of wilt symptoms, but does not significantly reduce E. tracheiphila infection success. This observation supports the hypothesis that reduced rates of wilt disease in ZYMV-infected plants reflect reduced visitation by beetle vectors. We also documented consistently strong SA responses to ZYMV infection, but limited responses to E. tracheiphila in the absence of ZYMV, suggesting that the latter pathogen may effectively evade or suppress plant defenses, although we observed no evidence of antagonistic cross-talk between SA and JA signaling pathways. We did, however, document effects of E. tracheiphila on induced responses to herbivory that may influence host-plant quality for (and hence pathogen acquisition by) cucumber beetles.

Pathogen effects on vegetative and floral odours mediate vector attraction and host exposure in a complex pathosystem.

Pathogens can alter host phenotypes in ways that influence interactions between hosts and other organisms, including insect disease vectors. Such effects have implications for pathogen transmission, as well as host exposure to secondary pathogens, but are not well studied in natural systems, particularly for plant pathogens. Here, we report that the beetle-transmitted bacterial pathogen Erwinia tracheiphila - which causes a fatal wilt disease - alters the foliar and floral volatile emissions of its host (wild gourd, Cucurbita pepo ssp. texana) in ways that enhance both vector recruitment to infected plants and subsequent dispersal to healthy plants. Moreover, infection by Zucchini yellow mosaic virus (ZYMV), which also occurs at our study sites, reduces floral volatile emissions in a manner that discourages beetle recruitment and therefore likely reduces the exposure of virus-infected plants to the lethal bacterial pathogen - a finding consistent with our previous observation of dramatically reduced wilt disease incidence in ZYMV-infected plants.

Pathway to dry skin prevention and treatment.

BACKGROUND: This article presents an evidence-supported clinical pathway for dry skin prevention and treatment. OBJECTIVE: The development of the pathway involved the following: a literature review was conducted and demonstrated that literature on dry skin is scarce. To compensate for the gap in the available literature, a modified Delphi method was used to collect information on prevention and treatment practice through a panel, which included 10 selected dermatologists who currently provide medical care for dermatology patients in Ontario. An advisor experienced in this therapeutic area guided the process, including a central meeting. Panel members completed a questionnaire regarding their individual practice in caring for these patients and responded to questions on assessment of dry skin etiology, frequency of skin care visits for consultation and follow-up, assessment, and referral to other specialties. The panel members reviewed a summary of all responses and reached a consensus. The result was presented as a clinical pathway. CONCLUSION: The panel concluded that our current awareness of dry skin and therefore prevention and effective treatment is limited; that identifying dry skin and its clinical issues requires tools such as clinical pathways, which may improve patient outcomes; and that additional research on dry skin etiology, prevention, and treatment is necessary.

Immunopathogenesis of hypersensitivity syndrome reactions to sulfonamides.

Cytokines play a role in the immunopathological and molecular mechanisms of sulfonamide-induced hypersensitivity reactions (HSRs). The objective of this study was to analyze the reliability and correlation between the clinical symptoms observed in affected patients (n = 86) because of a sulfonamide-induced HSR and their lymphocyte toxicity assay (LTA) values. Another goal was to determine the cytokine secretion in the patient's sera and their expression in the peripheral blood mononuclear cells (PBMCs) and to explore whether a correlation exists among positive LTA score, cytokine levels, and HSR occurrence. The final goal is to determine whether these measures could be used to predict the likelihood of a patient to experience an HSR during sulfonamide treatment. Such a predictive ability would be valuable to the clinician to know whether the patient would tolerate sulfonamides or whether an alternative antibiotic should be prescribed. The LTA showed a good correlation with the clinical involvement of patients with hypersensitivity syndromes. In addition, the pro-inflammatory cytokines presented significant differences in patients that had rash, fever, and organ involvement than in control patients or any of the other patient groups. Expression of tumor necrosis factor alpha (TNF-alpha) is significantly higher in patients presenting rash, fever, and organ involvement versus all other groups. It is concluded that a positive LTA is a predictor for sulfonamide-induced true HSR. In addition, T-helper cell 1 cytokines [TNF-alpha, interleukins (ILs) 1 and 2] as well as the chemokine regulated upon activation, normal T-cell expressed and secreted (RANTES) control the pathogenesis of sulfonamide-induced HSR and may be used in early diagnosis of the syndrome.

Drug interactions of clinical significance for the dermatologist: recognition and avoidance.

While it would be impossible for any dermatologist to remember all potential drug interactions, knowledge of the mechanisms of drug interactions can help reduce the risk of serious adverse outcomes. Most drugs are associated with interactions but the majority do not produce significant outcomes. Dealing with drug interactions is a challenge in all clinical practice, including dermatology. New information continues to appear, and dermatologists need to know about the drugs they use.This article focuses on the mechanisms of drug interactions. In particular, the life of a drug in terms of absorption, distribution, metabolism and excretion are reviewed with the focus on points of importance and relevance to drug interactions. The most clinically important drug interactions in dermatological practice are caused by alterations in drug metabolism. The contributions of P-glycoprotein, pharmacogenetic variation and genetic polymorphisms to drug interactions are highlighted, and the best evidence for drug interactions involving drug classes relevant to the dermatologist is presented. Since the initial evidence for clinically relevant drug interactions comes from case reports, prescribing physicians can have a major role in collating information on interactions. By understanding the mechanisms behind drug interactions and staying alert for toxicities, we can help make drug therapy safer and reduce the fear of drug interactions.

Reactive metabolites and adverse drug reactions: clinical considerations.

Idiosyncratic reactions can affect many different organ systems, either as -an isolated event (e.g., hepatitis) or as part of a syndrome (e.g., drug hypersensitivity syndrome). Formation of reactive metabolites of drugs in conjunction with a decreased ability for detoxification is believed to be the initiating step in many idiosyncratic reactions. The drug hypersensitivity syndrome, defined by the presence of fever, rash and internal organ involvement, is estimated to occur in approx 1 in 1000 to 1 in 10,000 exposures with drugs such as anticonvulsants sulfonamide antibiotics, allopurinol, and dapsone. Symptoms usually start within 2-8 wk of drug initiation. Serum sicknesslike reaction, most frequently found after 7-14 d of drug exposure, is distinguished by a fever, cutaneous eruption and arthralgias. Medications such as cefaclor, minocycline and bupropion are most frequently implicated in this reaction. In contrast, drug-induced lupus can occur l-2 yr after initiation of medication. Drug-induced lupus is characterized by musculoskeletal complaints and fever and weight loss. Drugs most commonly associated with drug-induced lupus include procainamide, hydralazine, chlorpromazine, isoniazid, and minocycline. Management of patients who develop idiosyncratic reactions includes discontinuation of the implicated drug, initiation of corticosteroids (when appropriate), and symptomatic relief as required. Internal organ involvement, which may initially be asymptomatic, should be monitored. Confirmatory or diagnostic tests are not readily available in most areas, except for research purposes.