No abstract

We demonstrate the use of the nematode Caenorhabditis elegans as a facile and inexpensive model host for several Gram-positive human bacterial pathogens. Enterococcus faecalis, Streptococcus pneumoniae, and Staphylococcus aureus, but not Bacillus subtilis, Enterococcus faecium, or Streptococcus pyogenes, kill adult C. elegans. Focusing our studies on the enterococcal species, we found that both E. faecalis and E. faecium kill C. elegans eggs and hatchlings, although only E. faecalis kills the adults. In the case of adults, a low inoculum of E. faecalis grows to a high titer in the C. elegans intestine, resulting in a persistent infection that cannot be eradicated by prolonged feeding on E. faecium. Interestingly, a high titer of E. faecium also accumulates in the nematode gut, but does not affect the longevity of the worms. Two E. faecalis virulence-related factors that play an important role in mammalian models of infection, fsr, a putative quorum-sensing system, and cytolysin, are also important for nematode killing. We exploit the apparent parallels between Gram-positive infection in simple and more complex organisms by using the nematode to identify an E. faecalis virulence factor, ScrB, which is relevant to mammalian pathogenesis. Gram-positive pathogens in the genera Streptococcus, Staphylococcus, and Enterococcus are leading causes of human infections, causing diseases such as pneumonia, meningitis, bacteremia, endocarditis, and necrotizing fasciitis. The genus Enterococcus, the main focus of this article, is particularly problematic because of multidrug resistance, including resistance to vancomycin, often the antibiotic of last resort. Nevertheless, only a limited number of enterococcal virulence-related factors have been described, including cytolysin (Cyl), a factor called aggregation substance (AS), a zinc metalloprotease (gelatinase), and fsr, a putative quorum-sensing system thought to be involved in gelatinase and͞or serine protease regulation (1-5). As the development of antibiotic resistance continues to erode one of the greatest advances in modern health care, it is crucial to identify bacterial targets that can form the basis of novel anti-infective therapies.One reason that relatively little is known about enterococcal virulence factors is that the mammalian models used to study enterococcal infections are cumbersome and expensive. Using a mammalian host to screen enterococcal mutant libraries for avirulent mutants, for example, would be prohibitively time consuming and expensive because of the large number of animals involved. Therefore, we have sought to develop alternative nonvertebrate hosts for Enterococcus and other Grampositive human pathogens.Previously, our laboratory and others have shown not only that the Gram-negative human pathogens Pseudomonas aeruginosa and Salmonella enterica kill the nematode Caenorhabditis elegans, but also that P. aeruginosa and S. enterica virulence factors required for mammalian pathogenesis also are required for efficient killing of C. elegans (6-10). In...

Google Flu Trends can detect regional outbreaks of influenza 7-10 days before conventional Centers for Disease Control and Prevention surveillance systems. We describe the Google Trends tool, explain how the data are processed, present examples, and discuss its strengths and limitations. Google Trends shows great promise as a timely, robust, and sensitive surveillance system. It is best used for surveillance of epidemics and diseases with high prevalences and is currently better suited to track disease activity in developed countries, because to be most effective, it requires large populations of Web search users. Spikes in search volume are currently hard to interpret but have the benefit of increasing vigilance. Google should work with public health care practitioners to develop specialized tools, using Google Flu Trends as a blueprint, to track infectious diseases. Suitable Web search query proxies for diseases need to be established for specialized tools or syndromic surveillance. This unique and innovative technology takes us one step closer to true real-time outbreak surveillance.