MicrobiologyBytes

How bacterial plant pathogens escape their fate

AJCann — Wed, 28 Jul 2010 08:00:19 +0000

The immune system of plants can be unstable in the face of rapidly evolving micro-organisms, and pathogens that can evade recognition can spread with alarming speed through a plant population. In this article in Microbiology Today, Gail Preston and Dawn Arnold ask, what is the reason for this inherent instability, and how can disease control be improved?

Plants, unlike animals, lack an adaptive immune system that allows them to recognize and defend against novel pathogenic micro-organisms. Instead they rely on a heritable, innate immune system in which plant receptors recognize the presence or activity of microbial molecules known as elicitors. Plants exposed to infection can increase the effectiveness of their immune system by increasing the speed and strength of their defence mechanisms. However, pathogens that have the ability to evade recognition can spread rapidly through plant populations. The instability of receptor-dependent resistance in the face of rapid microbial evolution creates one of the most fundamental challenges in plant breeding. In this article we discuss why receptordependent resistance breaks down in the face of pathogen evolution and consider whether knowledge of pathogen evolution can provide insights to improve disease control.

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HIV and the CCR5 coreceptor

AJCann — Mon, 26 Jul 2010 08:00:13 +0000

The C-C chemokine receptor type 5 (CCR5) is a key player in HIV infection due to its involvement in the infection process. Investigations into the role of the CCR5 coreceptor first focused on its binding to the virus and the molecular mechanisms leading to the entry and spread of HIV. The identification of naturally occurring CCR5 mutations has allowed scientists to address the CCR5 molecule as a promising target to prevent or limit HIV infection in vivo. Naturally occurring CCR5-specific antibodies have been found in exposed but uninfected people, and in a subset of HIV seropositive people who show long-term control of the infection. This suggests that natural autoimmunity to the CCR5 coreceptor exists and may play a role in HIV control. Such natural immunity has prompted strategies aimed at achieving anti-HIV humoral responses through CCR5 targeting.

From Natural Resistance to a New Anti-HIV Strategy. Viruses 2010, 2(2), 574-600 doi:10.3390/v2020574

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Agnowhat?

AJCann — Fri, 23 Jul 2010 08:00:18 +0000

Most non-enveloped viruses exit their host cells following cell lysis, which involves breakdown of the cell membrane and death of the host cell, and which is presumably the final result of an increase in plasma membrane permeability. JC virus (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML) and belongs to the polyomavirus family, which have non-enveloped virions. The extracellular release of mature progeny polyomavirus virions has been suggested to occur when cells disintegrate or rupture; however, the molecular mechanism(s) employed by JCV to induce cell lysis and facilitate virion release remain elusive. The late coding region of JCV encodes a small and basic regulatory protein, the agnoprotein, whose functions in the virus life cycle remain unclear. Viroporins are a group of proteins that modify the permeability of cellular membranes and promote the release of viral particles from infected cells. These proteins are not essential for the replication of viruses, but their presence often enhances virus growth. This paper demonstrates that the JCV agnoprotein forms homo-oligomers as an integral membrane protein and acts as a viroporin, and that expression of agnoprotein results in plasma membrane permeabilization and virion release. These observations suggest that the process of virion release of this non-enveloped DNA virus is highly regulated by a single virus protein.

The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin. 2010 PLoS Pathog 6(3): e1000801. doi: 10.1371/journal.ppat.1000801
Virus infections can result in a range of cellular injuries and commonly this involves both the plasma and intracellular membranes, resulting in enhanced permeability. Viroporins are a group of proteins that interact with plasma membranes modifying permeability and can promote the release of viral particles. While these proteins are not essential for virus replication, their activity certainly promotes virus growth. Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease resulting from lytic infection of oligodendrocytes by the polyomavirus JC virus (JCV). The genome of JCV encodes six major proteins including a small auxiliary protein known as agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to viral propagation at various stages in the replication cycle, including transcription, translation, processing of late viral proteins, assembly of virions, and viral propagation. Previous studies from our and other laboratories have indicated that JCV agnoprotein plays an important, although as yet incompletely understood role in the propagation of JCV. Here, we demonstrate that agnoprotein possesses properties commonly associated with viroporins. Our findings demonstrate that: (i) A deletion mutant of agnoprotein is defective in virion release and viral propagation; (ii) Agnoprotein localizes to the ER early in infection, but is also found at the plasma membrane late in infection; (iii) Agnoprotein is an integral membrane protein and forms homo-oligomers; (iv) Agnoprotein enhances permeability of cells to the translation inhibitor hygromycin B; (v) Agnoprotein induces the influx of extracellular Ca2+; (vi) The basic residues at amino acid positions 8 and 9 of agnoprotein key are determinants of the viroporin activity. The viroporin-like properties of agnoprotein result in increased membrane permeability and alterations in intracellular Ca2+ homeostasis leading to membrane dysfunction and enhancement of virus release.

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Tracking bacterial gene expression in the ocean

AJCann — Thu, 22 Jul 2010 08:00:24 +0000

How do marine microbial ecosystems respond to climate change and pollution? In this article in Microbiology Today, Jack Gilbert explains how treating microbial marine communities as single cells in a metatranscriptomics approach could shed light on this fundamental question:

If the number of known stars in the Milky Way is multiplied by the number of known galaxies in the universe the result is a huge number, a septillion (1×10²⁴). Yet, large as this is, it pales in comparison to the number of microbial cells found in the world oceans, estimated to be 1 nonillion (1×10³⁰). When we start to include soil, air and organism-associated environments, this number becomes unimaginable. Traditional microbiology is our gold standard for understanding how these trillions and trillions of bacteria function. Basically, we grow the bugs in a laboratory, one species at a time, and test how they respond to chemical stimuli. Ultimately, we sequence their genome and try to map their genes to particular functions. To help make this link we can observe the expression of these genes in response to certain stimuli, so called transcriptomics.

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PLoS: A Primer on Metagenomics

How RNA viruses maintain genome integrity

AJCann — Wed, 21 Jul 2010 08:00:45 +0000

A range of mechanisms exist to enable maintenance and restoration of genome integrity in RNA viruses. Despite their often fastidious mechanisms to ensure accurate replication initiation and termination, virus RNA-dependent RNA polymerases (RdRps) are sufficiently flexible to accommodate alternative modes of initiation and elongation, enabling terminal repair, terminal transferase activity and recombination. For any given virus, the behaviour of the RdRp at the 3′ end of a template might be impacted by the nature of the 3′-terminal sequence. It seems likely that, if the genome termini are intact and all promoter and accessory sequences required for replication initiation are present, the RdRp will engage preferentially in accurate replication initiation. However, if key terminal sequences are missing, the replicase complex might not be able to assemble correctly, releasing the RdRp to perform ‘abnormal’ actions, such as non-templated polymerization or terminal transferase activity. Once a genome has been repaired, the RdRp could revert to its ‘normal’ function of template-dependent polymerization.

Viruses that replicate in particularly harsh environments or which have no passive defences to protect their genomes may have replicases that accommodate alternative initiation mechanisms to facilitate terminal repair more readily, and fundamental differences in virus genome and replicase architecture probably affect the propensity for RNA recombination. It is striking that most examples of RNA virus genome repair involve positive-strand viruses, whose genomes might be more vulnerable than those of the double-stranded or negative-sense viruses, in which the genomes are sequestered in protein capsids during the entire cycle of infection. The data also suggest that formation of truncated genomes, whilst hindering virus replication kinetics, might allow or aid some viruses to become persistent, which ultimately could aid their propagation within the host population. Thus the capacity for genome repair could be an important factor in virus pathogenesis.

How RNA viruses maintain their genome integrity. 2010 J Gen Virol. 91(6): 1373-1387
RNA genomes are vulnerable to corruption by a range of activities, including inaccurate replication by the error-prone replicase, damage from environmental factors, and attack by nucleases and other RNA-modifying enzymes that comprise the cellular intrinsic or innate immune response. Damage to coding regions and loss of critical cis-acting signals inevitably impair genome fitness; as a consequence, RNA viruses have evolved a variety of mechanisms to protect their genome integrity. These include mechanisms to promote replicase fidelity, recombination activities that allow exchange of sequences between different RNA templates, and mechanisms to repair the genome termini. In this article, we review examples of these processes from a range of RNA viruses to showcase the diverse approaches that viruses have evolved to maintain their genome sequence integrity, focusing first on mechanisms that viruses use to protect their entire genome, and then concentrating on mechanisms that allow protection of the genome termini, which are especially vulnerable. In addition, we discuss examples in which it might be beneficial for a virus to ‘lose’ its genomic termini and reduce its replication efficiency.

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Microbial nanoscopy

AJCann — Tue, 20 Jul 2010 08:00:59 +0000

With its ability to observe single microbial cells at nanometre resolution, to monitor structural dynamics in response to environmental changes or drugs, and to detect and manipulate single-cell surface constituents, atomic force microscopy (AFM) provides new insight into the structure–function relationships of cell envelopes. This emerging field of microbial nanoscopy should have an important impact on many disciplines of microbiology, including cellular and molecular microbiology, pathogenesis, diagnosis, antimicrobial therapy and environmental microbiology.

How cell envelope constituents are organised and how they interact with the environment are key questions in microbiology. Unlike other bioimaging tools, AFM provides information about the nanoscale surface architecture of living cells and about the localization and interactions of their individual constituents. These past years have witnessed remarkable advances in our use of the AFM molecular toolbox to observe and force probe microbial cells. Recent milestones include the real-time imaging of the nanoscale organization of cell walls, the quantification of subcellular chemical heterogeneities, the mapping and functional analysis of individual cell wall constituents and the analysis of the mechanical properties of single receptors and sensors.

Microbial nanoscopy: a closer look at microbial cell surfaces. Trends Microbiol. Jul 12 2010

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Bacteria and IBD

AJCann — Mon, 19 Jul 2010 08:00:57 +0000

Inflammatory bowel disease (IBD) in humans, such as Crohn’s disease and ulcerative colitis, is a complex chronic inflammatory disorder of largely unknown cause in a genetically predisposed host. The incidence of these diseases varies widely between different countries, but overall has increased greatly in recent years, and IBD is now a major public health problem. The gastrointestinal tract of mammals is colonized by a vast range of microorganisms, and this intestinal microbiota is required for intestinal homeostasis and function. Tolerance towards commensal or symbiotic organisms must be maintained to benefit from this colonization. In contrast, colonization with specific pathogenic bacteria can be detrimental to the host, leading to infectious diseases. Thus the host has evolved numerous homeostatic responses towards microbial infections or harmless colonization on the one hand and host defence mechanisms on the other. The multifactorial mechanisms underlying IBD are emphasized by the number of host IBD susceptibility genes that have been identified in recent years. The contributions of the host immune system and the genetic factors that predispose to IBD have been extensively researched and reviewed. This review focuses on the role of bacteria in IBD.

The impact of the microbiota on the pathogenesis of IBD: lessons from mouse infection models. (2010) Nature Reviews Microbiology 8, 564-577 doi:10.1038/nrmicro2403
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a major human health problem. The bacteria that live in the gut play an important part in the pathogenesis of IBD. However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in establishing a healthy intestinal barrier and in its disruption is evolving only slowly. In recent years, mouse models of intestinal inflammatory disorders based on defined bacterial infections have been used intensively to dissect the roles of individual bacterial species and specific bacterial components in the pathogenesis of IBD. In this Review, we focus on the impact of pathogenic and commensal bacteria on IBD-like pathogenesis in mouse infection models and summarize important recent developments.

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Cyanobacteria

AJCann — Fri, 16 Jul 2010 08:00:07 +0000

Cyanobacteria are the most environmentally significant group of bacteria on Earth. In this article in Microbiology Today, David Adams explains how in many ways life on Earth owes its very existence to this ancient group of micro-organisms:

Cyanobacteria are a huge group of photosynthetic bacteria found in almost every environment on Earth, including many of those most inhospitable to life, such as hot springs, deserts and the Antarctic. They are also enormously abundant, particularly in the oceans, and are primary producers, meaning that they fix CO₂ and in many cases also N₂; as a consequence they have an immense influence on the planet’s nutrient cycles and even its weather. Life on Earth owes a further great debt to this group of bacteria because their evolution of oxygenic photosynthesis, in which oxygen is released from the splitting of water, resulted in the eventual oxygenation of the atmosphere, providing the stimulus for the evolution of complex life forms. In addition, cyanobacteria are the ancestors of plastids, the photosynthetic organelles of today’s algae and plants.

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Good news about chronic wasting disease

AJCann — Thu, 15 Jul 2010 08:00:16 +0000

Chronic wasting disease (CWD) is a prion disease affecting wild and captive deer. Like all mammalian prion diseases, which include Creutzfeldt-Jakob disease (CJD), kuru and variant CJD (vCJD) in humans and bovine spongiform encephalopathy (BSE) in cattle, the central event in CWD infection is the post-translational conversion of the host-encoded, cellular prion protein (PrPC), to an abnormal form called PrPSc. Progressive accumulation of PrPSc in the central nervous system is associated with clinical signs of CWD which includes weight loss, behavioural changes, excessive salivation, difficulty swallowing and ataxia prior to death. International concern over CWD is growing as infected cervids have now been reported in fourteen states in North America, two Canadian provinces and in South Korea. To date, CWD has not been reported in Europe, although surveillance has been limited.

The negative transmission data reported in this paper support the conclusion that the transmission barrier associated with the interaction of human PrP and these CWD prions is greater than that associated with interaction of human PrP and the prion strain causing epizootic BSE in cattle. This is good news from a human health perspective, but further studies will be required to evaluate the transmission properties of distinct deer prion strains as they are characterized.

Chronic wasting disease prions are not transmissible to transgenic mice over-expressing human prion protein. J Gen Virol. Jul 7 2010
Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk, and moose. CWD-infected cervids have been reported in fourteen US states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice over-expressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilised in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains; further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterised.