MicrobiologyBytes

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.

This article reviews recent research on Rift Valley fever virus (RVFV) infection, encompassing four main areas: epidemiology and outbreak prediction, viral pathogenesis, human diagnostics and therapeutics, and vaccine and therapeutic candidates. RVFV continues to extend its range in Africa and the Middle East. Better definition of RVFV-related clinical syndromes and human risk factors for severe disease, combined with early-warning systems based on remote-sensing, simplified rapid diagnostics, and tele-epidemiology, hold promise for earlier deployment of effective outbreak control measures. Advances in understanding of viral replication pathways and host cell-related pathogenesis suggest means for antiviral therapeutics and for more effective vaccination strategies based on genetically engineered virus strains or subunit vaccines. RVFV is a significant health and economic burden in many areas of Africa, and remains a serious threat to other parts of the world. Development of more effective methods for RVFV outbreak prevention and control remains a global health priority.

Advances in Rift Valley fever research: insights for disease prevention. Curr Opin Infect Dis. Jul 6 2010 doi: 10.1097/QCO.0b013e32833c3da6

Traditional treatment of bacterial infections relies heavily on the use of antibacterial compounds that either kill bacteria (bactericidal) or inhibit their growth (bacteriostatic). Typically, the targets for the main conventional antibiotics are essential cellular processes such as bacterial cell wall biosynthesis, bacterial protein synthesis, and bacterial DNA replication and repair. However, resistance to these drugs arises and spreads very rapidly, even to such an extent that bacteria have been identified that are simultaneously resistant to all available antibiotics. The increasing occurrence of resistant bacteria gradually renders antibiotics ineffective in treating infections and has enormous human and economic consequences worldwide. As a result, the identification of novel drug targets and the development of novel therapeutics constitute an important area of current scientific research. An alternative to killing or inhibiting growth of pathogenic bacteria is the specific attenuation of bacterial virulence, which can be attained by targeting key regulatory systems that mediate the expression of virulence factors. One of the target regulatory systems is quorum sensing (QS), or bacterial cell-to-cell communication. QS is a mechanism of gene regulation in which bacteria coordinate the expression of certain genes in response to the presence or absence of small signal molecules. As the importance of QS in virulence development of pathogenic bacteria became clear, about a decade ago, QS disruption was suggested as a new anti-infective strategy.

Although at this moment it is difficult to accurately estimate the risk of resistance development, this paper argues that scientists need to pay attention to the possibility that it will evolve. Once we have better knowledge of the risk of resistance development to QS disruption, it might be possible to direct further research on QS inhibition preferentially towards strategies that include a lower risk of resistance development.

Can Bacteria Evolve Resistance to Quorum Sensing Disruption? 2010 PLoS Pathog 6(7): e1000989. doi:10.1371/journal.ppat.1000989

The filamentous plant viruses of the family Potyviridae include almost a quarter of the known plant viruses. The family includes the genera Potyvirus, Rymovirus, Tritimovirus, Bymovirus, Maclurovirus, Ipomovirus and Brambyvirus. Potyvirid particles are approximately 7500 Å long and 120 Å in diameter and have helical pitches of about 33 Å. Circular dichroism measurements and secondary structure predictions suggest that the coat proteins are about 50% α-helical, similar to the potexviruses, and that the N- and C-termini of the coat proteins are located near the surface of the virions. Little other structural information was available for members of this family until recently. This paper shows that the potyvirids exhibit significant variation in helical symmetry, like the potexviruses and unlike the tobamoviruses.

Architecture of the potyviruses. Virology. Jul 1 2010 doi: 10.1016/j.virol.2010.06.013
X-ray fiber diffraction data were obtained and helical pitch and symmetry were determined for seven members of the family Potyviridae, including representatives from the genera Potyvirus, Rymovirus, and Tritimovirus. The diffraction patterns are similar, as expected. There are, however, significant variations in the symmetries, as previously found among the flexible potexviruses, but not among the rigid tobamoviruses. Wheat streak mosaic virus, the only member of the genus Tritimovirus examined, displayed the largest deviations in diffraction data and helical parameters from the other viruses in the group.

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Sporulation is a strategy used by many organisms, including bacteria, fungi, protozoa, algae, and ferns to survive conditions that are too harsh to sustain vegetative growth. Survival is generally facilitated by developing specialized cells (spores) with physical properties that confer resistance to environmental assault. Many organisms also produce spores on specialized structures that are adapted for efficient dispersal via wind or water currents. Through these adaptations, sporulation is an effective mechanism to either persist until local conditions improve or disperse to new environments conducive for growth.

For pathogenic microbes, favorable growth conditions are often found in a mammalian host, resulting in serious consequences for human health. For example, spores of protozoan parasites, such as the oocytes of Cryptosporidium sp., can be found in untreated or fecal waste-contaminated water and have been estimated to cause >50% of water-borne parasitic disease worldwide, including major outbreaks in the United States. Spores of bacterial pathogens, such as those produced by Bacillus anthracis, are extremely resistant to physical and chemical insult, making B. anthracis a potentially devastating biological weapon. In fungi, spores are thought to be the infectious particles of many fungal pathogens. This has been shown rigorously for a number of plant fungal pathogens, such as the wheat rusts, Puccinia sp., which disperse globally on an annual basis and cause damage to food crops totaling 3 billion dollars per year.

Among human fungal pathogens, spores are presumed infectious particles for many organisms. The infection-causing potential of spores from human fungal pathogens is exemplified by Coccidioides immitis, as few as 10 spores can establish disease and cause fatal disease. Because these highly infectious spores are adapted for wind dispersal, C. immitis spores, similar to spores from B. anthracis, have been postulated to be serious threats as biological weapons. Despite the demonstrated capacity of spores from human fungal pathogens to infect mammalian hosts, the specific roles that spores play in establishing disease are less clear.

Dueling in the lung: how Cryptococcus spores race the host for survival. Curr Opin Microbiol. Jun 4 2010
Many human fungal pathogens infect people when they are inhaled as spores. Despite the serious impact of fungal spores on human health, little is known about their basic properties or how they interact with the host. This is particularly true for Cryptococcus neoformans, a human fungal pathogen that causes more than 600,000 deaths annually. Spores of C. neoformans have not been well characterized previously because of technical challenges in isolating them; however, recent advances in spore isolation have lead to the first direct analyses of spores. Novel insights into the spore-host interaction, specifically how spores interact with alveolar macrophages, have provided a new model of cryptococcosis that could have broad implications for human fungal pathogenesis.

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Eukaryotic marine parasites could have a wide impact on marine ecology. This article in Microbiology Today describes the role of these parasites in processes as diverse as species competition, carbon cycling and gene transfer:

Parasites are typically small organisms that exploit their host both as a food source and as a habitat. Although well-studied as human pathogens and organisms prejudicial to human interests, they have been persistently ignored in microbial aquatic ecology. Increased awareness of the important role of viruses in marine aquatic ecosystems in processes as diverse as species competition, carbon cycling, and gene transfers has recently changed our overall view of aquatic parasites. Recent evidence of the widespread occurrence of small eukaryotic parasites, requiring eukaryotic hosts, has highlighted the existence of another kind of pathogen which potentially has specific ecological roles.

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Indoor environments, where the average person in an industrial nation spends ~90% of his or her life, represent the most important interface between humans and microbes. Examples of well-known fungi include a few human pathogens, allergens, agents of structural rot and food spoilers. Indoor fungi’s prominent role in successful litigation around the world contributes to rising costs for various industries and insurance companies. Increasingly strict standards for indoor sanitation have resulted in regulatory agencies and private industries seeking to quantify building health. Mould surveys that target the relatively few visibly apparent fungal species or those readily cultivable on artificial media are now standard, and a U.S. Environmental Protection Agency-developed set of real-time PCR probes facilitates their quantification. However, the recent rise in fungal infections caused by species formerly considered benign but now seen as causing disease in immunosuppressed humans, and a vastly increased resolution of indoor fungal composition afforded by culture-independent sampling methods, force us to reconsider what constitutes a normal indoor environment and the factors that shape it. Recent efforts to describe the processes shaping indoor and urban fungal composition show temporal effects and modest correlations with human activity. The existence of global-scale patterns in fungal composition, however, is unexamined, despite evidence of biogeographical patterning in other microbial systems.

As with larger organisms, bacterial and archaeal composition is determined by both the contemporary environment and historical processes such as dispersal. The relative importance of these factors and the particular environmental variables involved depend on the taxa and habitat sampled. For indoor fungi whose association with highly mobile humans presents opportunities for global dispersal, it was presumed that most taxa would be relatively cosmopolitan on a global scale, and that the local indoor environment (as determined by building function, construction material, or circulation system) would play a relatively large role in shaping composition. As a result of the combination of presumably high dispersal rates between indoor habitats and the highly selective indoor environment, little influence of the outdoor environment was expected on fungal composition. But are these assumptions true?

Indoor fungal composition is geographically patterned and more diverse in temperate zones than in the tropics. PNAS USA June 28 2010 doi: 10.1073/pnas.100045410
Fungi are ubiquitous components of indoor human environments, where most contact between humans and microbes occurs. The majority of these organisms apparently play a neutral role, but some are detrimental to human lifestyles and health. Recent studies that used culture-independent sampling methods demonstrated a high diversity of indoor fungi distinct from that of outdoor environments. Others have shown temporal fluctuations of fungal assemblages in human environments and modest correlations with human activity, but global-scale patterns have not been examined, despite the manifest significance of biogeography in other microbial systems. Here we present a global survey of fungi from indoor environments using both taxonomic and phylogeny-informative molecular markers to determine whether global or local indoor factors determine indoor fungal composition. Contrary to common ecological patterns, we show that fungal diversity is significantly higher in temperate zones than in the tropics, with distance from the equator being the best predictor of phylogenetic community similarity. Fungal composition is significantly auto-correlated at the national and hemispheric spatial scales. Remarkably, building function has no significant effect on indoor fungal composition, despite stark contrasts between architecture and materials of some buildings in close proximity. Distribution of individual taxa is significantly range- and latitude-limited compared with a null model of randomized distribution. Our results suggest that factors driving fungal composition are primarily global rather than mediated by building design or function.

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Group A rotaviruses (RVs) are important pathogens that cause acute, dehydrating gastroenteritis in infants and young children. The burden of disease is severe, particularly in developing countries where RV infections lead to more than 500,000 deaths annually. RVs are non-enveloped, triple-layered icosahedral particles that enclose an eleven-segmented, double-stranded (ds) RNA genome. The genome encodes six structural proteins (VP1–VP4, VP6, and VP7) and five or six non-structural proteins (NSP1–NSP5, and sometimes NSP6). Individual RV strains have traditionally been classified into serotypes based on the antibody responses generated against the outermost structural proteins VP7 (G-serotypes) and VP4 (P-serotypes). Due to the ease of sequencing, RVs are now classified into G/P-genotypes based on the relatedness of the genes encoding VP7 and VP4.

Although the mechanism by which RV infection leads to immunological protection is not fully understood, G/P-type-specific neutralizing antibodies have been shown to play an important role. Strains with particular G/P-type combinations are the most prevalent causes of disease in humans worldwide, and these are the targets of the two currently licensed RV vaccines. RotaTeq (Merck) contains five live-attenuated, reassortant viruses with human VP7 genes in a predominantly bovine RV background. In contrast, Rotarix (GlaxoSmithKline) is a live-attenuated, human RV containing genotype 1 internal genes. Both vaccines have proven safe and effective at protecting against severe diarrheal disease in industrialized countries and Latin America. However, the efficacy of RotaTeq and Rotarix in developing countries is expected to be reduced, which may be related to viral serotype diversity among other factors. Additionally, the high monetary cost of these current vaccines may limit their availability in regions of the world where they are most needed. As a result, there is a global health initiative to develop new RV vaccines that can be manufactured on-site at a lower cost. Two vaccine candidates being considered are the live-attenuated human strains RV3 and 116E.

Complete genome sequence analysis of candidate human rotavirus vaccine strains RV3 and 116E. Virology. Jun 25 2010
Rotaviruses (RVs) cause severe gastroenteritis in infants and young children; yet, several strains have been isolated from newborns showing no signs of clinical illness. Two of these neonatal strains, RV3 (G3P[6]) and 116E (G9P[11]), are currently being developed as live-attenuated vaccines. In this study, we sequenced the eleven-segmented double-stranded RNA genomes of cell culture-adapted RV3 and 116E and compared their genes and protein products to those of other RVs. Using amino acid alignments and structural predictions, we identified residues of RV3 or 116E that may contribute to attenuation or influence vaccine efficacy. We also discovered residues of the VP4 attachment protein that correlate with the capacity of some P[6] strains, including RV3, to infect newborns versus older infants. The results of this study enhance our understanding of the molecular determinants of RV3 and 116E attenuation and are expected to aid in the ongoing development of these vaccine candidates.

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• Rotavirus vaccines for the developing world
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The Komodo dragon (Varanus komodoensis) is the world’s largest lizard, with a mass up to 90 kg and a length of 3 m. It is restricted to five small islands in Eastern Indonesia where it is an apex predator, with adult lizards killing the largest ungulate prey found on the island – water buffalo, pigs and Timor deer – that often equal or exceed its own body mass. Individual dragons often kill their prey directly but also feed on carcasses of prey killed by other lizards or other agents. A large carcass enables multiple dragons to feed on one carcass at the same time.

In some cases, the ultimate demise of a prey is purportedly due to more than just direct bite induced trauma, involving bacterial sepsis acquired from the lizard’s bite or envenomation. Whilst direct bite inflicted injury is the most intuitive and oft observed mechanism to rapidly dispatch prey, the role of bacteria or venom to aid prey death is poorly known. In a study of multiple lizards, 58 species of bacteria were identified from the saliva and oral cavities, 93% of which are classified as potentially pathogenic. At least one species, tentatively identified as Pastuerella multocida, caused high mortality among mice injected with Komodo dragon saliva. Thus, the potential exists for bite-induced sepsis to contribute to prey mortality, but the bacteria may instead be coincidental to any effect on prey. Or are they?

Deathly Drool: Evolutionary and Ecological Basis of Septic Bacteria in Komodo Dragon Mouths. 2010 PLoS ONE 5(6): e11097. doi:10.1371/journal.pone.0011097
Komodo dragons, the world’s largest lizard, dispatch their large ungulate prey by biting and tearing flesh. If a prey escapes, oral bacteria inoculated into the wound reputedly induce a sepsis that augments later prey capture by the same or other lizards. However, the ecological and evolutionary basis of sepsis in Komodo prey acquisition is controversial. Two models have been proposed. The “bacteria as venom” model postulates that the oral flora directly benefits the lizard in prey capture irrespective of any benefit to the bacteria. The “passive acquisition” model is that the oral flora of lizards reflects the bacteria found in carrion and sick prey, with no relevance to the ability to induce sepsis in subsequent prey. A third model is proposed and analyzed here, the “lizard-lizard epidemic” model. In this model, bacteria are spread indirectly from one lizard mouth to another. Prey escaping an initial attack act as vectors in infecting new lizards. This model requires specific life history characteristics and ways to refute the model based on these characteristics are proposed and tested. Dragon life histories (some details of which are reported here) prove remarkably consistent with the model, especially that multiple, unrelated lizards feed communally on large carcasses and that escaping, wounded prey are ultimately fed on by other lizards. The identities and evolutionary histories of bacteria in the oral flora may yield the most useful additional insights for further testing the epidemic model and can now be obtained with new technologies.