Hot off the presses! Nov 01 Nat Rev Microbiol

The Nov 01 issue of the Nat Rev Microbiol is now up on Pubget (About Nat Rev Microbiol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

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  - Nat Rev Microbiol 9(11):761 (2011)
  
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  - Nat Rev Microbiol 9(11):762 (2011)
  
• Innate immunity: NAIPs give pathogens a warm reception | PDF (246 KB)
  - Nat Rev Microbiol 9(11):765 (2011)
  On bacterial infection, an inflammasome complex containing the NOD-like receptor (NLR) protein NLRC4 responds to flagellin and the rod component of type III secretion systems (T3SSs), and induces caspase 1 (CASP1) activation, cytokine production and pyroptotic cell death. However, a mechanistic understanding of how these different products are sensed and activate the NLRC4 inflammasome has been lacking.
• Fungal pathogenesis: Hungry fungus eats nematode | PDF (154 KB)
  - Nat Rev Microbiol 9(11):766 (2011)
  Nematophagous fungi can adopt a carnivorous lifestyle, during which they eat nematode worms. To do so, the cells organize themselves to form nets that trap nematodes, which are subsequently digested by the fungus.
• Fungal genetics: Killer sought in case of missing RNA interference | PDF (106 KB)
  - Nat Rev Microbiol 9(11):766 (2011)
  RNA interference (RNAi) systems were lost from the ancestors of some species of yeast but not from the ancestors of others. The authors investigated the consequences of restoring a functional RNAi system to Saccharomyces cerevisiae by introducing the genes encoding Argonaute and Dicer.
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  - Nat Rev Microbiol 9(11):766 (2011)
  
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  - Nat Rev Microbiol 9(11):766 (2011)
  
• Virology: Unusual escape for HCMV | PDF (141 KB)
  - Nat Rev Microbiol 9(11):766 (2011)
  The clinical development of a neutralizing antibody to treat human cytomegalovirus (HCMV)-associated retinitis in patients with AIDS was stopped at the Phase II–III stage owing to a lack of efficacy. At the time, it was suspected that the virus had developed resistance to the antibody, MSL-109, but the mechanism involved was unclear.
• Antimicrobials: Disruption of quorum sensing meets resistance | PDF (527 KB)
  - Nat Rev Microbiol 9(11):767 (2011)
  The use of drugs that specifically target mechanisms associated with virulence rather than cell growth has been suggested as a strategy to reduce the selective pressure that leads to antibiotic resistance in bacteria. However, Maeda et al.
• Bacterial toxins: Breaking the barrier | PDF (256 KB)
  - Nat Rev Microbiol 9(11):768 (2011)
  α-haemolysin, a pore-forming toxin produced by Staphylococcus aureus, was recently shown to bind the host cell metalloproteinase ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10). Bubeck Wardenburg and colleagues now find that this interaction is key to barrier disruption in epithelial cells during infection.
• Bacterial physiology: LCP proteins take the final step | PDF (213 KB)
  - Nat Rev Microbiol 9(11):768 (2011)
  In a recent paper in the EMBO Journal, Jeff Errington and colleagues describe a new family of bacterial cell wall assembly proteins, the LytR–Cps2A–Psr (LCP) family, members of which are responsible for the final step in the biogenesis of the bacterial cell wall.
• A new piece of the eukaryotic puzzle | PDF (391 KB)
  - Nat Rev Microbiol 9(11):769 (2011)
  This month's Genome Watch discusses the genome of the free-living amoeboflagellate protist Naegleria gruberi.
• In the news | PDF (277 KB)
  - Nat Rev Microbiol 9(11):770 (2011)
  Lasker victory for artemisinin researcher Chinese scientist Tu Youyou, of the China Academy of Chinese Medical Sciences, Beijing, has been recognized by the Albert and Mary Lasker Foundation with the prestigious Lasker–DeBakey Clinical Medical Research Award for her discovery of the antimalarial drug artemisinin. In the 1960s, Tu was working on a Chinese military project looking for a new antimalarial treatment targeting chloroquine-resistant parasites. One of the ancient Chinese herbal remedies Tu and her colleagues investigated was sweet wormwood (Artemisia annua), extracts of which have been used in Chinese medicine to treat fever for more than 2,000 years. The team identified an extract with strong antimalarial properties, which was subsequently modified to remove the toxic portion and used to develop artemisinin. Today, artemisinin is administered as a combination therapy to prevent the development of resistance. It is recommended by the WHO as the first-line treatment for malaria in regions where the disease! is endemic, and has saved million of lives, in particular in the developing world. New York Times/Financial Times TB vaccine hope A new type of vaccine for tuberculosis (TB) that elicits a strong immune response is reported in Nature Medicine. Currently, Mycobacterium bovis bacillus Calmette–Gurin (BCG), an attenuated form of M. bovis, is the only TB vaccine, but this has produced variable results and in fact shows very low efficacy in areas with a high number of TB cases. Jacobs and colleagues generated mutant Mycobacterium smegmatis lacking the secretion system Esx-3, which is conserved in mycobacteria and thought to have a key role in virulence. Injection of these bacteria at a high dose into mice activated a strong immune response and led to bacterial clearance from the tissues. Importantly, Jacobs and colleagues introduced Esx-3 from Mycobacterium tuberculosis into the mutant M. smegmatis and found that vaccination of mice with this strain (termed IKEPLUS) could induce robust immunity against M. tuberculosis, leading to clearance of bacteria in many tissues. Although further work is needed to de! termine the efficacy and safety of the vaccine, it is encouraging that IKEPLUS offered stronger protection against TB than M. bovis BCG, as well as a higher level of survival. Nature Medicine/BBC Linking malaria and bacteraemia Strategies to control malaria could also lower the rates of bacteraemia, which kills thousands of children every year in many parts of the world, in particular in Africa. A group at the Kenya Medical Research Institute (funded by the Wellcome Trust) in Kilifi examined the link between the two diseases by assessing rates of bacteraemia in children carrying one copy of the sickle cell gene, which naturally protects against malaria. They found that children carrying this 'sickle cell trait' were less likely to develop bacteraemia than those that lacked it. This was not because the two diseases are targeted by the same immune mechanism or because the sickle cell trait also protects against bacteraemia. Instead, in areas where malaria has nearly been eradicated (where the incidence of bacteraemia has also decreased), the protection against bacteraemia offered by the sickle cell trait disappeared. On the basis of these findings, the researchers suggest that malaria infection makes! children more susceptible to bacteraemia and may account for more than half of bacteraemia cases in malaria-endemic areas. Lancet/Science Daily New tick-borne disease identified Russian scientists have confirmed that the spirochaete Borrelia miyamotoi can cause tick-borne disease. B. miyamotoi is distantly related to Borrelia burgdorferi (which includes B. burgdorferi str. s.s., the causative agent of Lyme disease) and had previously been identified in ixodid tick vectors, which also carry B. burgdorferi. However, whether the species caused disease had been unclear. In collaboration with a group based at Yale University, New Haven, Connecticut, USA, the Russian group developed a diagnostic test that could distinguish disease caused by B. miyamotoi and B. burgdorferi. Using this test, they were able to conclude that B. miyamotoi causes disease in humans. Clinically, the disease resembles that caused by the other spirochaetes, albeit with a higher fever and incidence of relapse, and can be treated by the same drugs. Emerg. Infect. Dis. Outbreak news Poliovirus. Wild poliovirus 1 (WPV1) has appeared in China for the first time since 1999. The virus was isolated from four young children from the Hotan Prefecture, Xinjiang Uygur Autonomous Region, China, who have been left paralyzed. A team of specialists, including epidemiologists and laboratory experts, has been dispatched in the area to investigate this outbreak, and China plans to vaccinate a large number of children in the region to avoid further spread. The virus is genetically related to the WPV1 currently present throughout Pakistan, where the only cases of WPV3 infection in Asia have also been reported. WHO/Nature News Listeriosis. Up to 13 listeriosis-associated deaths and 72 cases of illness have been reported throughout the United States, all caused by eating contaminated cantaloupe melons. The melons, which were confirmed to contain Listeria monocytogenes by the US Food and Drug Administration, were traced back to a farm in Holly, Colorado, USA, that distributes the fruit throughout the country. As the bacterium has a long incubation period, the CDC expects the number of cases to increase. New York Times/The Guardian 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 his Twitter page (@Ojcius).
• De novo generation of prion strains
  - Nat Rev Microbiol 9(11):771 (2011)
  Prions are self-replicating proteins that can cause neurodegenerative disorders such as bovine spongiform encephalopathy (also known as mad cow disease). Aberrant conformations of prion proteins accumulate in the central nervous system, causing spongiform changes in the brain and eventually death. Since the inception of the prion hypothesis — which states that misfolded proteins are the infectious agents that cause these diseases — researchers have sought to generate infectious proteins from defined components in the laboratory with varying degrees of success. Here, we discuss several recent studies that have produced an array of novel prion strains in vitro that exhibit increasingly high titres of infectivity. These advances promise unprecedented insight into the structure of prions and the mechanisms by which they originate and propagate.
• Regulation of growth and death in Escherichia coli by toxin–antitoxin systems
  - Nat Rev Microbiol 9(11):779 (2011)
  Escherichia coli K-12 contains at least 36 toxin genes, the expression of which causes growth inhibition and eventual death. These toxins are usually co-expressed with their cognate antitoxins in operons called toxin–antitoxin (TA) modules. Under normal growth conditions, toxins and antitoxins form stable complexes. However, stress-induced proteases preferentially eliminate unstable antitoxins, releasing free toxins to inhibit various cellular functions. TA systems have important roles in the physiology of cells in their natural habitats, including functions in biofilm formation and multidrug resistance. In this Review, we describe these TA systems in light of their functions and roles in the regulation of cell growth and death.
• Microbial ultraviolet sunscreens
  - Nat Rev Microbiol 9(11):791 (2011)
  Exposure to the shortest wavelengths in sunlight, ultraviolet light, constitutes a deleterious ecological factor for many microorganisms. The use of secondary metabolites as sunscreens has emerged as an important photoprotective mechanism in certain groups of large-celled microorganisms, such as cyanobacteria, fungi and many protists. In this Review, we describe our current understanding of microbial 'sunscreen' compounds, including scytonemin, the mycosporines and the naphthalene-based melanins. Study of these sunscreens has led to the discovery of new classes of compounds, new metabolic pathways, a deeper understanding of microbial photobiology and the potential for dermatological or biomedical applications.
• Microbial degradation of aromatic compounds — from one strategy to four
  - Nat Rev Microbiol 9(11):803 (2011)
  Aromatic compounds are both common growth substrates for microorganisms and prominent environmental pollutants. The crucial step in their degradation is overcoming the resonance energy that stabilizes the ring structure. The classical strategy for degradation comprises an attack by oxygenases that hydroxylate and finally cleave the ring with the help of activated molecular oxygen. Here, we describe three alternative strategies used by microorganisms to degrade aromatic compounds. All three of these methods involve the use of CoA thioesters and ring cleavage by hydrolysis. However, these strategies are based on different ring activation mechanisms that consist of either formation of a non-aromatic ring-epoxide under oxic conditions, or reduction of the aromatic ring under anoxic conditions using one of two completely different systems.
• Non-transcriptional regulatory processes shape transcriptional network dynamics
  - Nat Rev Microbiol 9(11):817 (2011)
  Information about the extra- or intracellular environment is often captured as biochemical signals that propagate through regulatory networks. These signals eventually drive phenotypic changes, typically by altering gene expression programmes in the cell. Reconstruction of transcriptional regulatory networks has given a compelling picture of bacterial physiology, but transcriptional network maps alone often fail to describe phenotypes. Cellular response dynamics are ultimately determined by interactions between transcriptional and non-transcriptional networks, with dramatic implications for physiology and evolution. Here, we provide an overview of non-transcriptional interactions that can affect the performance of natural and synthetic bacterial regulatory networks.