authoritative, comprehensive and systematic

Innate receptors for adaptive immunity

Vesicular mechanisms of traffic of fungal molecules to the extracellular space

Cryptococcus neoformans constitutes an ideal model organism to unravel the contribution of cellular aging to the virulence of chronic infections

The role of ‘eat-me’ signals and autophagy cargo receptors in innate immunity

Fungal glycan interactions with epithelial cells in allergic airway disease

Fungal cell wall dynamics and infection site microenvironments: signal integration and infection outcome

The fungal Achilles’ heel: targeting Hsp90 to cripple fungal pathogens

Titan cells in Cryptococcus neoformans: cells with a giant impact

Candida albicans biofilms: building a heterogeneous, drug-tolerant environment

Signaling diversity and evolution of extracytoplasmic function (ECF) s factors

Type VI secretion: a beginner's guide

Type VI secretion is a newly described mechanism for protein transport across the cell envelope of Gram-negative bacteria. Components that have been partially characterised include an IcmF homologue, the ATPase ClpV, a regulatory FHA domain protein and the secreted VgrG and Hcp proteins. Type VI secretion is clearly a key virulence factor for some important pathogenic bacteria and has been implicated in the translocation of a potential effector protein into eukaryotic cells by at least one…

Volume 11, Issue 1, 01 February 2008, Pp 3-8
Bingle, L.E. | Bailey, C.M. | Pallen, M.J.

The mechanisms of carbon catabolite repression in bacteria

Carbon catabolite repression (CCR) is the paradigm of cellular regulation. CCR happens when bacteria are exposed to two or more carbon sources and one of them is preferentially utilised (frequently glucose). CCR is often mediated by several mechanisms, which can either affect the synthesis of catabolic enzymes via global or specific regulators or inhibit the uptake of a carbon source and thus the formation of the corresponding inducer. The major CCR mechanisms operative in Enterobacteriaceae…

Volume 11, Issue 2, 01 April 2008, Pp 87-93
Deutscher, J.

The type VI secretion system: translocation of effectors and effector-domains

A number of prominent Gram-negative bacteria use the type VI secretion system (T6SS) to transport proteins across the bacterial envelope. Rapid progress is being made in elucidating the structural components of the T6SS apparatus, and a few effectors have been reported to pass through it. However, this is not the complete story: a family of T6SS proteins, the VgrGs, share structural features with the cell-puncturing device of the T4 bacteriophage, and may be used in a similar fashion by…

Volume 12, Issue 1, 01 February 2009, Pp 11-17
Pukatzki, S. | McAuley, S.B. | Miyata, S.T.

Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules

Bacteria employ sophisticated cell-to-cell communication or 'quorum sensing' (QS) systems for promoting collective behaviours that depend on the actions of one or more chemically distinct diffusible signal molecules. As determinants of cell population density, multiple QS systems are often integrated with each other and within global regulatory networks and subject to the prevailing environmental conditions as well as the presence and activities of other organisms. QS signal molecules, although…

Volume 12, Issue 2, 01 April 2009, Pp 182-191
Williams, P. | Cámara, M.

Comparative genomics: the bacterial pan-genome

Bacterial genome sequencing has become so easy and accessible that the genomes of multiple strains of more and more individual species have been and will be generated. These data sets provide for in depth analysis of intra-species diversity from various aspects. The pan-genome analysis, whereby the size of the gene repertoire accessible to any given species is characterized together with an estimate of the number of whole genome sequences required for proper analysis, is being increasingly…

Volume 11, Issue 5, 01 October 2008, Pp 472-477
Tettelin, H. | Riley, D. | Cattuto, C. | Medini, D.

Alarming β-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae

Resistance to β-lactams and other antibiotics in the Enterobacteriaceae is frequently associated with plasmidic resistance determinants that are easily transferred among species. β-Lactamase-mediated resistance is increasingly associated with plasmid-encoded extended-spectrum β-lactamases (ESBLs) and carbapenemases, specifically the CTX-M family of ESBLs, the KPC family of serine carbapenemases, and the VIM, IMP, and NDM-1 metallo-β-lactamases. Although clonal dispersion of resistant isolates…

Volume 13, Issue 5, 01 October 2010, Pp 558-564
Bush, K.

A renaissance for the pioneering 16S rRNA gene

Culture-independent molecular surveys using the 16S rRNA gene have become a mainstay for characterizing microbial community structure over the past quarter century. More recently this approach has been overshadowed by metagenomics, which provides a global overview of a community's functional potential rather than just an inventory of its inhabitants. However, the pioneering 16S rRNA gene is making a comeback in its own right thanks to a number of methodological advancements including higher…

Volume 11, Issue 5, 01 October 2008, Pp 442-446
Tringe, S.G. | Hugenholtz, P.

Control of bacterial transcription, translation and replication by (p)ppGpp

The small nucleotides pppGpp and ppGpp (or (p)ppGpp) are rapidly synthesized in response to nutritional stress. In Escherichia coli, the enzymes RelA and SpoT are triggered by different starvation signals to produce (p)ppGpp. In many Gram-positive bacteria this is carried out by RelA and two small homologs. (p)ppGpp, along with the transcription factor DksA, has profound effects on transcription initiation in E. coli. (p)ppGpp/DksA exert differential effects on promoters by playing upon their…

Volume 11, Issue 2, 01 April 2008, Pp 100-105
Srivatsan, A. | Wang, J.D.

Salmonella takes control: effector-driven manipulation of the host

Salmonella pathogenesis relies upon the delivery of over thirty specialised effector proteins into the host cell via two distinct type III secretion systems. These effectors act in concert to subvert the host cell cytoskeleton, signal transduction pathways, membrane trafficking and pro-inflammatory responses. This allows Salmonella to invade non-phagocytic epithelial cells, establish and maintain an intracellular replicative niche and, in some cases, disseminate to cause systemic disease. This…

Volume 12, Issue 1, 01 February 2009, Pp 117-124
McGhie, E.J. | Brawn, L.C. | Hume, P.J. | Humphreys, D. | Koronakis, V.

Pseudomonas syringae type III secretion system effectors: repertoires in search of functions

The ability of Pseudomonas syringae to grow and cause diseases in plants is dependent on the injection of multiple effector proteins into plant cells via the type III secretion system (T3SS). Genome-enabled bioinformatic/experimental methods have comprehensively identified the repertoires of effectors and related T3SS substrates for P. syringae pv. tomato DC3000 and three other sequenced strains. The effector repertoires are diverse and internally redundant. Insights into effector functions are…

Volume 12, Issue 1, 01 February 2009, Pp 53-60
Cunnac, S. | Lindeberg, M. | Collmer, A.

The role of Hfq in bacterial pathogens

The ubiquitous RNA-binding protein, Hfq, has been shown to be required for the fitness and virulence of an increasing number of bacterial pathogens. Mutants lacking Hfq are often sensitive to host defense mechanisms and highly attenuated in animal models, albeit there is considerable variation in both severity and extent of phenotypes. RNomics and deep sequencing (RNA-seq) approaches discovered the small RNA and mRNA targets of Hfq, and indicated that this protein might impact on the expression…

Volume 13, Issue 1, 01 February 2010, Pp 24-33
Chao, Y. | Vogel, J.

Bacteriophage lysins as effective antibacterials

Lysins are highly evolved enzymes produced by bacteriophage (phage for short) to digest the bacterial cell wall for phage progeny release. In Gram-positive bacteria, small quantities of purified recombinant lysin added externally results in immediate lysis causing log-fold death of the target bacterium. Lysins have been used successfully in a variety of animal models to control pathogenic antibiotic resistant bacteria found on mucosal surfaces and infected tissues. The advantages over…

Volume 11, Issue 5, 01 October 2008, Pp 393-400
Fischetti, V.A.

Antibiotics as signals that trigger specific bacterial responses

The ecological and evolutionary roles of antibiotics have been usually inferred from their therapeutical activity. Since those compounds inhibit bacterial growth, it was thought that they should be produced by soil microorganisms to inhibit the growth of competitors in natural habitats. It has been shown however that antibiotics modulate transcription of bacteria in a dose dependent manner. Furthermore, each antibiotic triggers a specific response, and those responses may have adaptive values.…

Volume 11, Issue 2, 01 April 2008, Pp 161-167
Fajardo, A. | Martínez, J.L.

ESX/type VII secretion systems and their role in host-pathogen interaction

The ESX-1 system is responsible for the secretion of the prototypic ESX proteins, namely the 6 kDa early secreted antigenic target (ESAT-6) and the 10 kDa culture filtrate protein (CFP-10). These two proteins, which form a 1:1 heterodimeric complex, are among the most important proteins of Mycobacterium tuberculosis involved in host-pathogen interaction. They induce a strong T cell mediated immune response, are apparently involved in membrane and/or host-cell lysis and represent key virulence…

Volume 12, Issue 1, 01 February 2009, Pp 4-10
Simeone, R. | Bottai, D. | Brosch, R.

The clinical consequences of antimicrobial resistance

The continued evolution of antimicrobial resistance in the hospital and more recently in the community threatens to seriously compromise our ability to treat serious infections. The major success of the seven-valent Streptococcus pneumoniae vaccine at reducing both infection and resistance has been followed by the emergence of previously minor serotypes that express multiresistance. The almost universal activity of cephalosporins and fluoroquinolones against community Escherichia coli strains…

Volume 12, Issue 5, 01 October 2009, Pp 476-481
Rice, L.B.

New insights into transcriptional regulation by H-NS

H-NS, a nucleoid-associated DNA-binding protein of enteric bacteria, was discovered 35 years ago and subsequently found to exert widespread and highly pleiotropic effects on gene regulation. H-NS binds to high-affinity sites and spreads along adjacent AT-rich DNA to silence transcription. Preferential binding to sequences with higher AT-content than the resident genome allows H-NS to repress the expression of foreign DNA in a process known as 'xenogeneic silencing.' Counter-silencing by a…

Volume 11, Issue 2, 01 April 2008, Pp 113-120
Fang, F.C. | Rimsky, S.

Role of Pseudomonas aeruginosa type III effectors in disease

Pseudomonas aeruginosa uses a type III secretion system (T3SS) to directly inject four known effectors into host cells. ExoU is a potent cytotoxin with phospholipase A2 activity that causes rapid necrotic death in many cell types. The biological function of ExoY, an adenylate cyclase, remains incompletely defined. ExoS and ExoT are closely related bifunctional proteins with N-terminal GTPase activating protein (GAP) activity toward Rho family proteins and C-terminal ADP ribosylase (ADPRT)…

Volume 12, Issue 1, 01 February 2009, Pp 61-66
Engel, J. | Balachandran, P.

New developments in microbial interspecies signaling

There is a growing appreciation that in addition to well-documented intraspecies quorum sensing systems, small molecules act as signals between microbes of different species. This review will focus on how bacterial small molecules modulate these interspecies interactions. We will particularly emphasize complex relationships such as those between microbes and insects, interactions resulting in non-antagonistic outcomes (i.e. developmental and morphological processes), how co-culture can lead to…

Volume 12, Issue 2, 01 April 2009, Pp 205-214
Shank, E.A. | Kolter, R.

Plant pathogenic bacterial type III effectors subdue host responses

Like animals, plants sense bacterial pathogens through surface-localized pattern recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat proteins (NB-LRR) and trigger defense responses. Many plant-pathogenic bacteria secrete a large repertoire of effector proteins into host cells to modulate host responses, enabling successful infection and multiplication in plants. A number of these effector proteins target plant innate immunity signaling pathways, while others…

Volume 11, Issue 2, 01 April 2008, Pp 179-185
Zhou, J.-M. | Chai, J.

Bacteriophage genomics

The past three years have seen an escalation in the number of sequenced bacteriophage genomes with more than 500 now in the NCBI phage database, representing a more than threefold increase since 2005. These span at least 70 different bacterial hosts, with two-thirds of the sequenced genomes of phages representing only eight bacterial hosts. Three key features emerge from the comparative analysis of these genomes. First, they span a very high degree of genetic diversity, suggesting early…

Volume 11, Issue 5, 01 October 2008, Pp 447-453
Hatfull, G.F.

SagA of CagA in Helicobacter pylori pathogenesis

Much attention has recently been given to the role of the Helicobacter pylori CagA protein, the only as yet identified H. pylori protein that is delivered into the host gastric epithelial cells by a type IV secretion system, in the development of H. pylori-associated diseases, including gastric carcinoma. This review summarizes the latest advances in our understanding of pathogenic actions of H. pylori CagA, particularly focusing on the molecular mechanisms underlying CagA entry into the host…

Volume 11, Issue 1, 01 February 2008, Pp 30-37
Hatakeyama, M.

New microbial fuels: a biotech perspective

Bioethanol and plant oil-derived biodiesel are generally considered first generation biofuels. Recognizing their apparent disadvantages, scientists and engineers are developing more sustainable and economically feasible second generation biofuels. The new microbial fuels summarized here have great potential to become viable replacements or at least supplements of petroleum-derived liquid transportation fuels. Yields and efficiencies of the four metabolic pathways leading to these microbial…

Volume 12, Issue 3, 01 June 2009, Pp 274-281
Rude, M.A. | Schirmer, A.

Activation of gene expression by small RNA

Small regulatory RNAs (sRNAs) commonly act to downregulate gene expression. In bacteria, however, sRNAs have also been shown to activate genes by a variety of direct or indirect mechanisms. Several sRNAs (DsrA, GlmZ, RNAIII, RprA, RyhB, and Qrr) act as direct translational activators by an 'anti-antisense mechanism' in the 5′ mRNA region to liberate a sequestered ribosome binding site, while pairing of GadY sRNA to the 3′-end alters processing and increases stability of its target mRNA.…

Volume 12, Issue 6, 01 December 2009, Pp 674-682
Fröhlich, K.S. | Vogel, J.

The effector repertoire of enteropathogenic E. coli: ganging up on the host cell

Diarrhoeal disease caused by enteropathogenic E. coli (EPEC) is dependent on a delivery system that injects numerous bacterial 'effector' proteins directly into host cells. The best-described EPEC effectors are encoded together on the locus of enterocyte effacement (LEE) pathogenicity island and display high levels of multifunctionality and cooperativity within the host cell. More recently, effectors encoded outside the LEE (non-LEE effectors) have been discovered and their functions are…

Volume 12, Issue 1, 01 February 2009, Pp 101-109
Dean, P. | Kenny, B.

The Salmonella-containing vacuole-Moving with the times

Salmonella pathogenesis is dependent on its ability to invade and replicate within host cells. Following invasion the bacteria remain within a modified phagosome known as the Salmonella-containing vacuole (SCV), within which they will survive and replicate. Invasion and SCV biogenesis are dependent on two Type III secretion systems, T3SS1 and T3SS2, which are used to translocate distinct cohorts of bacterial effector proteins into the host cell. Elucidating the roles of individual effector…

Volume 11, Issue 1, 01 February 2008, Pp 38-45
Steele-Mortimer, O.

Inflammasomes and host defenses against bacterial infections

Studying bacterial transcriptomes using RNA-seq

Microbial diversity and function in soil: from genes to ecosystems

Single cell genomics: an individual look at microbes

CRISPR-based adaptive immune systems

Ribosome heterogeneity: another level of complexity in bacterial translation regulation

Exploiting social evolution in biofilms

Uropathogenic Escherichia coli virulence and innate immune responses during urinary tract infection

Entering the era of bacterial epigenomics with single molecule real time DNA sequencing

Determinants of specificity in two-component signal transduction