Review Articles in 2009

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.

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.

Almost one-quarter of the calories consumed by the global human population is derived from rice. Epidemics of rice blast disease, which are caused by the filamentous fungusMagnaporthe oryzae, therefore represent a major threat to global food stocks. This Review discusses how functional genomic approaches are shedding light on the mechanisms used by M. oryzaeduring plant infection.

It is not easy to study how microbial communities function. Microbial community proteogenomics, which integrates genomics, ecology, biological mass spectrometry and informatics, could help us to unravel the physiology, ecology and evolution of microbial populations and communities.

New sequencing methods have enabled the assembly of whole microbial genomes in a matter of days, greatly expanding the volume and scope of microbial sequencing efforts. This article reviews the current capabilities of the various high-throughput sequencing technologies and data analysis tools in the context of their application to microbial genomics.

The outbreaks of severe acute respiratory syndrome (SARS) between 2002 and 2004 killed hundreds of people. Vaccines against the SARS coronavirus (SARS-CoV) could protect the population during future outbreaks. In this Review, Shibo Jiang and colleagues describe such vaccines, as well as other therapeutics, based on the SARS-CoV spike protein.

Formation of disulphide bonds between cysteine residues is key for the stability and activity of a range of exported bacterial proteins. Disulphide bond formation occurs during the oxidative protein folding processes that are catalysed by the DSB protein family. In this article, Heras and colleagues review oxidative folding pathways inEscherichia coliK12 and other bacteria and their impact on pathogenesis.

Considerable advances have been made in the field of outer membrane protein biogenesis during the past year. The β-barrel assembly machinery (BAM) mediates efficient insertion of folded β-barrels into the outer membrane of Gram-negative bacteria. The role of the BAM in the folding of membrane proteins is discussed in this Review.

Apoptosis is associated with virus-induced human diseases of the central nervous system, heart and liver, and causes morbidity and mortality. Animal models of virus-induced diseases provide insights into the role of apoptosis in pathogenesis, the pathways involved and potential therapeutic implications.

Bluetongue virus is a substantial health risk to sheep and other ruminants. Livestock can be protected by vaccination, but as described in this Review, current vaccines can have severe drawbacks. New molecular techniques will provide safer and more effective vaccines and allow for better surveillance of the spread of vaccine strains.

Microorganism- and host-derived signals can stimulate formation of a multiprotein complex called the inflammasome, which activates the cysteine protease caspase 1. In turn, caspase 1 triggers an inflammatory programmed cell death pathway known as pyroptosis. Numerous pathogens have evolved a mechanism to subvert pyroptosis and persist within infected cells.

Metalloproteins constitute up to one-third of the total cellular cohort of proteins, and cells have evolved elaborate mechanisms for scavenging and storing metal atoms. In this Review, the authors summarize the homeostatic mechanisms by which bacteria and archaea ensure that metalloproteins receive and bind the correct metal.

Humans contract Buruli ulcer following infection withMycobacterium ulcerans, a slow-growing toxin producer that evolved from Mycobacterium marinum. Both M. ulcerans and M. marinum are waterborne, but M. ulceransis associated with various insects that might serve as vectors. This Review summarizes recent findings and explains how the toxin, a polyketide called mycolactone, acts on immune cells.

In the filamentous bacteriaStreptomyces, morphological differentiation is closely integrated with fundamental growth and cell-cycle processes, as well as with truly complex multicellular behaviour. Important progress is being made towards understanding the intriguing processes that underlie growth and morphogenesis in Streptomyces.