Getting nosey with S. aureus
How can we prevent Staphylococcus aureus infections, given that resistance to antibiotics is on the rise and effective vaccinations remain elusive? One solution may be directly under our noses. Approximately 20% of the human population carries strains of S. aureus in their nasal cavities. Not only are these strains responsible for around 80% of invasive S. aureus infections, but individuals with persistent nasal S. aureus colonization are more likely to develop infection. But to therapeutically target S. aureus nasal colonization, which could reduce infection, it would be useful to first determine the S. aureus colonization factors. To this end, Heiman Wertheim, from the University Medical Center Rotterdam, the Netherlands, and colleagues inoculated 16 healthy individuals (or 32 healthy nostrils) with 2 strains of S. aureus (1 for each nostril). Whereas one nostril received a wild-type strain, the other received a mutant that lacked the cell-wall protein clumping factor B (ClfB); ClfB enables colonization in mice, but its importance for human colonization was unknown. After 2 weeks, the wild-type strain persisted in 3 volunteers, whereas the mutant strain persisted in none. These findings indicate that ClfB is necessary for human nasal colonization and might be a potential target for strategies to reduce S. aureus infection. PLoS Med.
Ebola declawed
By generating a 'safe' form of Ebola virus, researchers may have made it possible for research laboratories around the world to study Ebola. Because Ebola virus causes deadly haemorrhagic fever, has a 50–90% mortality rate and cannot be treated, the virus can currently only be studied in laboratories that are rated at biosafety level 4 (BSL4) — the highest rating. Peter Halfmann, from the University of Wisconsin–Madison, United States, and colleagues removed the gene that encodes VP30, a transcription factor that is crucial for viral replication, from the Ebola genome. Consequently, the modified Ebola strain, which is genetically stable and morphologically indistinguishable from wild-type Ebola, can only reproduce inside genetically modified cells that express VP30. So, if the modified Ebola virus escapes from the Petri dish, laboratory workers need not fear infection. If approved by national regulatory bodies — and if safeguards can be met to ensure that the 'contained' virus is not inadvertently converted back into the lethal form — Ebola may be coming soon to a BSL2 or BSL3 laboratory near you. PNAS/Nature
Listeria 's hideaway
Listeria monocytogenes can cause acute infection in pregnant and immunocompromised individuals, and replicates rapidly in the cytosol of host cells. Curiously, the bacteria can also persist inside vacuoles in liver granuloma macrophages, with unknown effect. John Brumell, from the Hospital for Sick Children, Toronto, Canada, and colleagues now report that the toxin listeriolysin O (LLO) promotes the formation of so-called spacious Listeria-containing phagosomes (SLAPs), which enable the pathogen to establish persistent infections. In the livers of severe combined immunodeficient mice and in macrophages in vitro, the authors observed L. monocytogenes in compartments they named SLAPs. Whereas phagosomes naturally mature into degradative phagolysosomes, SLAPs do not. Although L. monocytogenes can replicate inside SLAPs (in ∼8 hours), the rate is far slower than in the cytosol (∼40 minutes). Intriguingly, SLAP formation depends on the expression of the bacterial protein LLO and on autophagy. The authors suggest that SLAPs represent a stalemate between L. monocytogenes and its host; the host prevents rapid colonization by forcing the bacteria into SLAPs, but is unable to fully eliminate the bacteria. Nature
Syphilis sailed the ocean blue
Syphilis — once called the 'French disease' by the Italians, the 'Spanish disease' by the Dutch and the 'Christian disease' by the Arabs — was imported from South America by Columbus and his sailors, report Kristin Harper, from Emory University, United States, and colleagues. Two competing, although unverified, theories had been postulated for the emergence of syphilis in Europe. First reported in 1495, some say that syphilis circulated in Europe for centuries before it became virulent and was recognized; others propose that Columbus brought it over from the Americas. Harper and colleagues built a phylogenetic tree by comparing 21 genetic regions of 26 disparate strains of Treponema species, including the subspecies that causes syphilis. The syphilis-causing strains were most closely related to, although evolutionarily younger than, South American yaws-causing strains. As yaws is a tropical disease that is transmitted by skin–skin contact, the first syphilis-causing strain would have needed to evolve into a venereal form before it could spread between heavily clad Europeans in cooler climates. Some researchers, however, want to see a comparison of the full genomes, rather than only the 21 regions, before they will be convinced that syphilis was really a case of Montezuma's revenge. PLoS Negl. Trop. Dis./Science
Neil Smith
Google gives
With an informal company motto of “Don't be evil”, it is fitting that Google pledged 1% of the firm's equity, annual profits and employees' time “to address some of the world's most urgent problems” when they went public in 2004. Now, Larry Brilliant, Director of Google.org, has announced that the organization will fund five philanthropic initiatives, which will include the development of early warning systems for emerging threats, such as infectious diseases. Their approach to these systems is twofold: first, identify hot spots, and second, enable a rapid response. To this end, Google.org is funding various projects, such as InSTEDD (Innovative Support to Emergencies, Diseases and Disasters), which will build platforms to rapidly detect and respond to health threats, and HealthMap, which will study how online data can be used in disease surveillance. Spending is currently far less than the 1% that was initially pledged, but if the pilot projects do well then Google's giving is expected to increase. Google.org/Economist
Probing probiotics
Twenty-four patients died in probiotic clinical trials between 2004 and 2007, according to researchers from the University Medical Centre in Utrecht, the Netherlands. During the studies, species of Lactobacillus, Enterococcus or Bifidobacterium were administered to 296 patients to treat inflammation of the pancreas. Both the International Probiotics Association and the European Food and Feed Cultures Association stress, however, that all volunteers were critically ill before the trials began and that the probiotics were administered directly into the intestine through a tube. An investigation has been launched to determine the exact cause of the deaths, and Dutch doctors have been advised not to give probiotics to patients with organ failure or who are in intensive care.
But it's not all bad news for probiotics. A study in Molecular Systems Biology shows, for the first time, that orally administered probiotics can be beneficial for the make-up of the gut microbiota and for metabolic processes (see The bacteria diet, pages 174–175). BBC/Food and Drink Europe/The Telegraph
The shape of resistance
For H5N1 to spread among humans, the haemagglutinin (HA) must first adapt so that it can bind to the sialylated glycans that line the epithelial cells of the airways and lungs in humans. Currently, H5N1 HA has high specificity for the avian-like α2,3 sialylated glycans, but poor specificity for human-like α2,6 sialylated glycans. Aarthi Chandrasekaran and colleagues from the Massachusetts Institute of Technology, United States, used various techniques to investigate how HA specificity is determined. Their findings revealed that it is the structural topology, rather than the biochemical linkage, of the sialylated glycans that determines specificity. Whereas avian α2,3 sialylated glycans are cone shaped, human α2,6 sialylated glycans are umbrella shaped. Thus, a preference for cone-shaped sialylated glycans may have stopped H5N1 from spreading throughout the human population. The authors suggest that arrays of umbrella-shaped α2,6 sialylated glycans may be useful tools to monitor whether avian 'flu viruses are adapting to human hosts. Nature Biotechnol./BBC
Open wide
Waiting several days, and performing several diagnostic tests, to find out which virus is causing a cough might be a thing of the past. Two tests that identify respiratory viruses in only a few hours have been certified by the Food and Drug Administration (FDA). xTAG, which is manufactured by Luminex Molecular Diagnostics, will be used in the United States to test for the presence of 12 respiratory viruses — including various influenza subtypes and adenoviruses, respiratory syncytial virus A and B, and rhinovirus. In Europe, xTAG is certified to test for an additional eight viruses, including the virus that causes SARS (severe acute respiratory syndrome). ProFlu+, which is manufactured by Prodesse, tests for only four viruses: influenza A and B, and respiratory syncytial virus A and B. However, what ProFlu+ lacks in scope, it makes up for in accuracy and speed. According to the FDA, “other diagnostic tests for respiratory viruses are fast but not as accurate, or are accurate but not as rapid.” Samples for both tests are acquired by swabbing the back of the throat. By improving the speed at which we can identify respiratory viruses, these tests will help doctors prescribe antivirals when they are most effective — within 2 days of the onset of symptoms. FDA
Novel virus linked to cancer
Merkel cell carcinoma (MCC) is a rare, but extremely aggressive, form of skin cancer. It tends to occur on sun-exposed areas of the body, but is more common in people who are immunocompromised, including patients with AIDS. In addition, its incidence has tripled in the United States in the past 20 years. Although these findings suggest that MCC may have an infectious origin, no causative agent has been identified. To investigate this possibility, Patrick Moore and colleagues from the University of Pittsburgh Cancer Institute, United States, screened MCC skin samples for non-human DNA. Although 8 of the 10 MCC samples possessed a polyomavirus, only 4 of the 25 control skin samples possessed the virus. As this virus had never been identified before, the authors named it Merkel cell polyomavirus (MCV). Further analysis revealed that MCV DNA was integrated into the genomes of six of the eight MCC tumours. Taken together, these findings suggest that MCV might be a contributing factor in MCC pathogenesis. Science
Outbreak news
Cholera. More than 1,700 cases of cholera were reported in January in the Democratic Republic of the Congo, according to Médecins Sans Frontières. Most cases have affected people from poor regions near large cities, such as Lubumbashi, Bukama and Likasi. Cholera has a 50% mortality rate if left untreated. Médecins Sans Frontières
Rift Valley fever. Sudan's outbreak of Rift Valley fever seems to have ended. Only one new case, in Gazeera state, was reported in January. In total, there were 698 confirmed cases and 222 deaths across 6 Sudanese states. WHO
In the News was compiled with the assistance of David Ojcius, University of California, Merced, USA. David's links to infectious disease news stories can be accessed on Connotea ( http://www.connotea.org ), under the username ojcius.