Biofilms are a principal form of microbial growth and are critical to development of clinical infection. They are responsible for a broad spectrum of microbial infections in the human host. Many medically important fungi produce biofilms, including Candida, Aspergillus, Cryptococcus, Trichosporon, Coccidioides, and Pneumocystis. This review emphasizes common features among fungal biofilms and points toward genes and pathways that may have conserved roles.
Many bacteria can actively take up DNA from their environment, a genetically programmed ability called natural competence. When this DNA recombines and changes the cell’s genotype, the cell is said to be transformed. Natural competence has previously never been directly demonstrated in Escherichia coli, and most transformation instead relies on artificial permeabilisation to bring DNA into cells:
Natural DNA Uptake by Escherichia coli. (2012) PLoS ONE 7(4): e35620. doi:10.1371/journal.pone.0035620 Escherichia coli has homologues of the competence genes other species use for DNA uptake and processing, but natural competence and transformation have never been detected. Although we previously showed that these genes are induced by the competence regulator Sxy as in other gamma-proteobacteria, no conditions are known that naturally induce sxy expression. We have now tested whether the competence gene homologues encode a functional DNA uptake machinery and whether DNA uptake leads to recombination, by investigating the effects of plasmid-borne sxy expression on natural competence in a wide variety of E. coli strains. High- and low-level sxy expression alone did not induce transformation in any of the strains tested, despite varying the transforming DNA, its concentration, and the incubation conditions used. Direct measurements of uptake of radiolabelled DNA were below the limit of detection, however transformants were readily detected when recombination functions were provided by the lambda Red recombinase. This is the first demonstration that E. coli sxy expression can induce natural DNA uptake and that E. coli‘s competence genes do encode a functional uptake machinery. However, the amount of transformation cells undergo is limited both by low levels of DNA uptake and by inefficient DNA processing/recombination.
Tuberculosis (TB) and HIV co-infections place an immense burden on health care systems and pose particular diagnostic and therapeutic challenges. Infection with HIV is the most powerful known risk factor predisposing for Mycobacterium tuberculosis infection and progression to active disease, which increases the risk of latent TB reactivation 20-fold. TB is also the most common cause of AIDS-related death. Thus, M. tuberculosis and HIV act in synergy, accelerating the decline of immunological functions and leading to subsequent death if untreated. The mechanisms behind the breakdown of the immune defense of the co-infected individual are not well known. The aim of this review is to highlight immunological events that may accelerate the development of one of the two diseases in the presence of the co-infecting organism.
The term “prion” was originally coined by Prusiner to explain the unusual infectious agent in transmissible spongiform encephalopathies (TSEs, also known as prion disease). Now the term has expanded to include a growing list of fungal proteins that stably maintain an atypical self-propagating conformation and epigenetically modify a variety of cellular processes. Although fungal prions and the TSE agent share the capability of maintaining an atypical self-propagating conformation, fungal prions distinctly differ from the TSE agent in several aspects. Thus far, the TSE agent is the only prion that behaves as a bona fide infectious agent, having an infectious cycle, capable of transmitting horizontally (among a community) and causing epidemic outbreaks.
A key concept of the prion hypothesis is that prion is a self-propagating PrP conformer, which elicits the conversion of host-encoded normal PrPC to pathogenic PrPSc. Polyanions, such as RNA molecules and proteoglycans, have been identified as one type of cofactors in the brain homogenate that enhance prion propagation. Lipids are another type of cofactors that promote prion propagation in cell-free conversion assay and in propagating recombinant prions.
Virion Assembly Factories in the Nucleus of Polyomavirus-Infected Cells. (2012) PLoS Pathog 8(4): e1002630. doi:10.1371/journal.ppat.1002630
Polyomaviruses are infectious pathogens of mammals and birds that have been linked to the development of cancers in their hosts. Members of the polyomavirus family are associated with human disease, such as JCV and BKV, and over the past few years, several more human polyomaviruses (WUV, KIV and MCV) have been discovered in immune-suppressed individuals. We are studying the way in which these viruses assemble in cells in order to identify critical points where anti-viral therapies could target these viruses. Using a structural, biochemical and cell biological approach, we set out to define sites of virus assembly and virus intermediates. We identified virus-specific structures that we termed “virus factories”. We believe that these sites serve as an assembly line for the production of new viruses. Our study provides new evidence for the presence and composition of virus assembly factories, and identifies a host protein that may be important for infection by polyomaviruses.
Continually faced with changing environmental conditions, free-living bacteria are under enormous pressure to develop new traits and gain a selective advantage over competing strains. Crucial to bacterial adaptation and survival is the ability to obtain new genetic material via horizontal gene transfer (HGT). HGT, which has been described as ‘evolution in quantum leaps’, allows bacteria to rapidly acquire novel functions such as the ability to survive within eukaryotic host cells, combat other bacteria, and gain resistance to antimicrobial agents. Despite their potential benefits, however, newly acquired sequences are particularly problematic to bacteria.
Silencing of foreign DNA in bacteria. Current Opinion in Microbiology 19 January 2012
Xenogeneic silencing proteins facilitate horizontal gene transfer by silencing expression of AT-rich sequences. By virtue of their activity these proteins serve as master regulators of a variety of important functions including motility, drug resistance, and virulence. Three families of silencers have been identified to date: the H-NS like proteins of Gram-negative bacteria, the MvaT like proteins of Pseudomonacae, and the Lsr2 proteins of Actinobacteria. Structural and biochemical characterization of these proteins have revealed that they share surprising commonalities in mechanism and function despite extensive divergence in both sequence and structure. Here we discuss the mechanisms that underlie the ability of these proteins to selectively target AT-rich DNA and the contradictory data regarding the mode by which H-NS forms nucleoprotein complexes.
VacA toxin from the cancer-inducing bacterium Helicobacter pylori is currently classified as a pore-forming toxin but is also considered a multifunctional toxin, apparently causing many pleiotropic cell effects. However, an increasing body of evidence suggests that VacA could be the prototype of a new class of monofunctional A-B toxins in which the A subunit exhibits pore-forming instead of enzymatic activity. Thus, VacA may use a peculiar mechanism of action, allowing it to intoxicate the human stomach. By combining the action of a cell-binding domain, a specific intracellular trafficking pathway and a novel mitochondrion-targeting sequence, the VacA pore-forming domain is selectively delivered to the inner mitochondrial membrane to efficiently kill target epithelial cells by apoptosis.
While affecting all age groups, respiratory syncytial virus (RSV) infections can be particularly severe in infants, who develop functionally distinct immune responses, as well as in immunocompromised individuals. The extent to which environmental, viral and host factors contribute to the pathogenesis of RSV varies considerably between infected individuals. A correlation between the level of virus replication and pathogenesis has been established, and several viral proteins, in particular NS1 and NS2, modulate the immune response. Host immunity clearly contributes to RSV pathogenesis, and a number of specific cell populations may be involved. Ultimately, whether the response induced by RSV is protective or pathogenic depends on a combination of host factors, young age being one of the most important ones.
