Reviews & Analysis

To evade immune responses in mammalian hosts, many pathogens use complex genetic systems to vary the surface antigens that are recognized by host defences. In this Review, Kirk Deitsch and colleagues highlight how bacterial, protozoan and fungal pathogens from distinct evolutionary lineages have evolved surprisingly similar mechanisms for antigenic variation.

The evolution and molecular characteristics of theMycobacterium tuberculosiscomplex are hotly debated. Here, Noel Smith and colleagues address several misconceptions about the origins of tuberculosis that have arisen over the years.

Galectins are important for recognition of carbohydrate ligands during embryogenesis, development and immune regulation. In addition, recent work has shown that galectins also function as receptors for glycans expressed on the surface of potentially pathogenic microorganisms. In this Review, Gerardo Vasta discusses the roles of galectins in host immunity and how pathogens have evolved to evade or subvert galectin-mediated immune responses.

Tagging eukaryotic proteins with ubiquitin can target them for proteasomal degradation. However, despite the presence of proteasomes in several bacterial and all archaeal species, prokaryotic homologues of ubiquitin were presumed to be absent. In this Progress article, Heran Darwin describes the characterization of a prokaryotic ubiquitin-like protein (Pup) that is covalently attached to proteins, resulting in their proteasome-mediated degradation.

Using large-scale, systems biology approaches, we can now systematically map synergistic and antagonistic interactions between drugs. Consequently, drug antagonism is providing us with insight into the functions and relatedness of cellular components, mechanisms of drug action and novel ways to inhibit the evolution of antibiotic resistance.

Coronaviruses gained prominence during the SARS outbreaks of 2002–2003, but there are many different coronaviruses that infect humans and animals. Perlman and Netland describe the biology of the coronaviruses, including their replication, host immune response and interspecies transmission.

Cleavage of membrane proteins by intramembrane proteases can release effector domains that carry out a range of cellular functions. In higher eukaryotes, the functions of such proteases are well characterized. However, the importance of such proteases in unicellular organisms is only recently being appreciated. In this article, Sin Urban reviews the recent advances in our understanding of how intramembrane proteases play pivotal parts in a range of pathogenic microorganisms.

The host cell and intracellular pathogens are in a continuous struggle. Flannagan, Cosío and Grinstein describe the pathway by which the bacteria are taken up, the antimicrobial mechanisms of the host cell and the different ways bacteria evade these mechanisms.

Movies, made possible by the combination of time-lapse microscopy, quantitative image analysis and fluorescent protein reporters, are allowing us to directly observe various cellular components over time in individual cells. As such, movies are providing powerful insights into the behaviour of genetic circuit behaviours in diverse microbial systems.

For diseases that are both rare and lethal, it is difficult to test vaccines. Sullivan and colleagues describe the use of immune correlates and the animal rule for the licensing of Ebola vaccines.

The malaria parasite exports an array of proteins while it resides in the erythrocytes of its host. This Review describes the functions of parasite proteins that interact with the erythrocyte membrane skeleton or that promote delivery of the major virulence protein, PfEMP1, to the erythrocyte membrane.

Many bacterial pathogens can invade non-phagocytic cells and survive within a membrane-bound vacuole. However, few pathogens are able to escape the vacuoles and proliferate in the host cell cytosol. In this Review, Tang and colleagues discuss the mechanisms by which these pathogens enter the cytosol, obtain nutrients and subvert host immune responses.

The mammalian intestine is colonized by complex indigenous bacterial communities that establish beneficial symbiotic relationships with their host, making important contributions to host metabolism and digestive efficiency. In this Opinion article, Lora Hooper explores the roles of immune suppression, evasion and subversion in the establishment of these important symbiotic relationships.

Bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) was recently identified as a second messenger in bacteria that regulates a wide range of phenotypes, including biofilm formation and motility. The discovery that the enzymes that make and break c-di-GMP are widespread in the bacterial world highlighted their central importance in bacterial physiology, but raised questions about the specificity of the signalling. Regine Hengge describes the mechanisms and evolutionary variations of c-di-GMP signalling.

Neisseria meningitidisandNeisseria gonorrhoeaeshare extensive genetic and antigenic similarities but have distinct lifestyles and niche preferences. In this Review, Mumtaz Virji examines the mechanisms underlying niche establishment and the challenges posed by the rapidly modulated surface structures of these bacteria to vaccine development.

The use of microbial fuel cells to generate electrical current is increasingly being seen as a viable source of renewable energy production. In this Progress article, Bruce Logan highlights recent advances in our understanding of the mechanisms used by exoelectrogenic bacteria to generate electrical current and the important factors to consider in microbial fuel cell design.

The pathogenesis of HIV-1 is markedly different to that of most simian immunodeficiency viruses (SIVs). Frank Kirchhoff proposes a model in which the presence ofvpuin HIV-1 and a small number of SIV strains allowed changes in the Nef proteins that contribute to these differences.

Rhizobia are a diverse group of soil bacteria that induce the formation of nitrogen-fixing nodules on the roots of legumes. In this Opinion article, a group of proteins that are secreted by rhizobia, some of which have homologues in bacterial pathogens, are used to support the hypothesis that some pathogenic pathways have been co-opted by rhizobia for symbiotic purposes.

Viruses are widespread and come in many shapes and sizes. They play an important part in the evolution of many species. But are they alive and should they be included as part of the tree of life? Moreira and López-García discuss ten reasons why they should be excluded.

Synthetic biology will provide the potential to redesign, or even build from scratch, specialized organisms to carry out complex tasks. In this Opinion article, Nitin Baliga and colleagues argue that to achieve the integrated framework for such complex bioengineering, a convergence of the fields of synthetic biology and systems biology will be required.