MicrobiologyBytes

Time – the emerging dimension of plant virus studies

AJCann — Mon, 09 Nov 2009 17:00:35 +0000

Recent research has revealed that some plant viruses, like many animal viruses, have measurably evolving populations. Most of these viruses have single-stranded positive-sense RNA genomes, but a few have single-stranded DNA genomes. The studies show that extant populations of these virus species are only decades to centuries old, and the genera in which they are placed have diverged since agriculture was invented, and spread around the world during the Holocene. We suggest that this is not mere coincidence but evidence that the conditions generated by agriculture during this era have favoured particular viruses. There is also evidence, albeit less certain, that some plant viruses, including a few shown to have measurably evolving populations, have much more ancient origins. We discuss the possible reasons for this clear discordance between short-term and long-term evolutionary rate estimates, and how it might result from a large timescale dependence of the evolutionary rates. We also discuss briefly why it is useful to know the rates of evolution of plant viruses.

Time – the emerging dimension of plant virus studies. J Gen Virol. Nov 4 2009

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Fact Sheet on Guillain-Barré syndrome

AJCann — Fri, 06 Nov 2009 17:00:43 +0000

CDC have recently published the following fact sheet on Guillain-Barre syndrome (GBS), a rare disorder (wrongly) thought to be frequently associated with influenza infection:

Guillain-Barré syndrome is rare
Guillain-Barré syndrome (GBS) is a rare disorder in which a person’s own immune system damages the nerves, causing muscle weakness and sometimes paralysis. GBS can cause symptoms that last for as little as a few weeks, or go on for several months. Most people recover fully from GBS, but some people have nerve damage that does not go away. In rare cases, people have died of GBS, usually from not being able to breathe due to weakness of their breathing muscles.

GBS may have several causes
While it is not fully known what causes GBS, it is known that about two-thirds of people who get GBS do so several days or weeks after they have been sick with diarrhea or a lung or sinus illness. An infection with the bacterium Campylobacter jejuni, which can cause diarrhea, is one of the most common illnesses linked to GBS. Although rare, people can also get GBS after having the flu or other infections such as Epstein Barr virus. Except for the swine flu vaccine used in 1976, no other flu vaccines have been clearly linked to GBS.

GBS is more common in older adults
Anyone can get GBS, but it is far more common in adults than children. Adults over 50 years of age are 2-3 times more likely to get GBS than younger people. Each year, between 6,000 and 9,100 people in the United States get GBS. This means that about 140 people get GBS every week.

Getting GBS from a vaccination is very rare
In very rare cases, someone may develop GBS in the days or weeks after getting a vaccination. In 1976, there was a small increased chance of GBS after getting a flu (swine flu) vaccination. This means about 1 more case per 100,000 people who got the swine flu vaccine.

Many studies have looked at seasonal flu vaccines and GBS
Since 1976, many studies have been done to see if other flu vaccines may cause GBS. In most studies no link was found between the flu vaccine and GBS. However, two studies did suggest that about 1 more person out of 1 million people vaccinated with seasonal flu vaccine may develop GBS. This continues to be studied. For the most part, the chance of getting very ill from flu is far higher than the chance of getting GBS after getting the flu vaccine.

CDC has many systems to identify GBS cases
Since GBS is a serious disorder that people get every year, CDC has developed several GBS surveillance systems. These are tracking systems to better see whether some GBS cases are linked to flu vaccinations. During the 2009-2010 flu season, CDC and FDA will be closely looking at reports of serious problems, including GBS, which may be linked to the use of the 2009 H1N1 flu vaccine and to the seasonal flu vaccine. These systems already include some vaccination safety systems, such as the Vaccine Adverse Event Reporting System (VAERS), and new systems, such as the CDC Emerging Infections Program and a partnership with the American Academy of Neurology, which includes doctors who are most likely to see people with GBS. None of these systems existed in 1976. Through these systems, CDC and FDA will be able to find any possible link between GBS and seasonal or 2009 H1N1 flu vaccines early in the vaccination program and take action.

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Campylobacter jejuni

Cell division in rod-shaped bacteria

AJCann — Thu, 05 Nov 2009 17:00:00 +0000

Cell division is a highly complex cytological process to produce viable progeny. Rod-shaped bacteria often divide with high precision at midcell to produce two equally sized daughter cells. In virtually all cells cytokinesis requires cytoskeletal elements. In bacteria the tubulin homolog FtsZ is the central cell division protein that assembles into a cytoskeletal scaffold known as the Z-ring. Subsequently, other proteins that drive invagination of cell membrane and synthesis of cell wall material are recruited to the division site. It has long been known that cell division in rod-shaped bacteria is restricted to midcell, between the segregated nucleoids.

In the last decades research has revealed that two inhibitory systems are involved in the spatial regulation of cytokinesis. The Min system has been shown to prevent aberrant cell division close to the cell poles, while nucleoid occlusion prevents cell division from occurring over the nucleoids. The current models suggest that the target of the inhibitory mechanism is the cytoskeletal element FtsZ and that the concerted action of nucleoid occlusion and Min are necessary for correct placement of the division machinery. However, recent advances show that at least the Min system also ensures that division occurs only once in a cell cycle and might also act downstream of FtsZ assembly. The combined action of these two negative regulators of FtsZ assembly defines the site of septation in many rod-shaped bacteria. Recent discoveries have added to the knowledge about the mechanism how the division machinery is spatially regulated and opened up new, unexpected, insights into division site selection.

Division site selection in rod-shaped bacteria. Curr Opin Microbiol. Oct 31 2009

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Solving the mystery of BK virus transmission

AJCann — Wed, 04 Nov 2009 17:00:10 +0000

BK virus (BKV) belongs to the polyomavirus family and is ubiquitous in the human population. The viral capsid is icosahedral and has a diameter of 45–50 nm. The genome consists of a closed circular double-stranded DNA molecule with approximately 5 kb. BKV infection typically occurs during childhood, without specific symptoms, followed by a state of non-replicative infection in various tissues, with the urogenital tract as the principal site. In the setting of relative or absolute cell-mediated immunosuppression, dramatic increase in BK viral replication occurs, resulting in the lytic destruction of infected uroepithelial cells, which in turn induces the influx of inflammatory immune cells. This destruction of kidney cells most often occurs in 5–8% of kidney transplants resulting in organ loss in half of these cases and is termed BKV-associated nephropathy. Rise in the incidence of Polyomavirus viruria and viremia has been detected in recipients of bone marrow, kidney and heart transplants, as well as an increase in viruria in HIV-infected individuals. The potential for BK replication at distant sites such as the salivary gland may certainly exist in the setting of HIV infection.

While it is clear that BKV infection is an ubiquitous childhood infection, BKV transmission is not currently well understood. The present studies were undertaken to determine whether BKV could infect and replicate within salivary gland cells resulting in virus production and potentially transmission. BKV has been detected in the saliva of patients with HIV-associated salivary gland pathology and in healthy individuals. In order to begin to decipher BKV pathogenesis within the salivary gland cell it was essential to develop an in vitro model system. Submandibular and parotid gland cell lines were able to support virus entry, transcription, translation and virion production and BKV infection could be inhibited by saturating the capsid protein with its ganglioside receptor. This data demonstrates for the first time, BKV detection in saliva and evidence that human salivary gland cells can be productively infected with BK virus. This suggests that while kidney/uroepithelial cells have long been known to be a site of BKV replication and latency, the salivary gland may also constitute an infectious reservoir for BKV. Although the natural route of BKV transmission has not been resolved, this study suggests a potential for oral BKV transmission.

BK virus has tropism for human salivary gland cells in vitro: Implications for transmission. Virology Sep 24 2009
In this study, it was determined that BKV is shed in saliva and an in vitro model system was developed whereby BKV can productively infect both submandibular (HSG) and parotid (HSY) salivary gland cell lines. BKV was detected in oral fluids using quantitative real-time PCR (QRTPCR). BKV infection was determined using quantitative RT-PCR, immunofluorescence and immunoblotting assays. The infectivity of BKV was inhibited by pre-incubation of the virus with gangliosides that saturated the major capsid protein, VP1, halting receptor mediated BKV entry into salivary gland cells. Examination of infected cultures by transmission electron microscopy revealed 45-50 nm BK virions clearly visible within the cells. Subsequent to infection, encapsidated BK virus was detected in the supernatant. We thus demonstrated that BKV was detected in oral fluids and that BK infection and replication occur in vitro in salivary gland cells. These data collectively suggest the potential for BKV oral route of transmission and oral pathogenesis.

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Signals of growth regulation in bacteria

AJCann — Tue, 03 Nov 2009 17:00:58 +0000

A fundamental characteristic of living cells is their ability to regulate growth in response to changing environmental conditions. This review focuses on recent progress toward understanding the mechanisms by which bacterial growth is regulated. These phenomena include the ‘viable but not culturable’ (VBNC) state, in which bacterial growth becomes conditional, and ‘persistence’, which confers antibiotic resistance to a small fraction of bacteria in a population. Notably, at least one form of persistence appears to involve the generation of nongrowing phenotypic variants after transition through stationary phase. The possible roles of toxin-antitoxin modules in growth control are explored, as well as other mechanisms including contact-dependent growth inhibition, which regulates cellular metabolism and growth through binding to an outer membrane protein receptor.

This review focuses on recent advances in our understanding of bacterial growth regulation, with an emphasis on the mechanisms that control entry and exit from a slow growth or nongrowth (dormant) state, excluding spore formation. This topic has relevance to a number of important aspects of bacterial biology including resistance of a small fraction of a bacterial population to killing by an antibiotic, termed “persistence”. The maintenance of bacterial viability without growth impacts human health in a number of ways including maintenance of pathogen reservoirs and chronic infections such as tuberculosis and melioidosis. This has been a difficult area of research, in part due to phenotypic variability in which only a small fraction of bacteria are within a dormant state in a population, making it hard to isolate and study dormant cells. Moreover, since many genes influence cell growth, it has been a challenge to identify those that constitute specific pathway(s) for dormancy/antibiotic resistance. The aim of this review is to delineate some of the key findings and concepts in growth control, bringing together new developments in different fields of research that may impinge on one another.

Signals of growth regulation in bacteria. Curr Opin Microbiol. Oct 22 2009

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Replication cycle of chikungunya virus

AJCann — Mon, 02 Nov 2009 17:59:20 +0000

The unprecedented 2005-2006 epidemics of chikungunya virus (CHIKV) in the French Reunion Island in the Indian Ocean, followed by several outbreaks in other parts of the world such as India, have attracted the attention of clinicians, scientists, and state authorities about the risks linked to this re-emerging mosquito-borne virus. CHIKV, which belongs to the Alphaviruses genus, was not previously regarded as a highly pathogenic arbovirus. However, this opinion was challenged by the death of several CHIKV-infected persons in Reunion Island. The epidemic episode began in December 2005 and four months later the seroprevalence survey report indicated that 236,000 persons, more than 30% of Reunion Island population, had been infected with CHIKV, among which 0.4-0.5% of cases were fatal. Since the epidemic peak, the infection case number has continued to increase to almost 40% of the population, with a total of more than 250 fatalities.

Although information available on CHIKV is growing quite rapidly, we are still far from understanding the strategies required for the ecologic success of this virus, virus replication, its interactions with its vertebrate hosts and arthropod vectors, and its genetic evolution. This paper summarizes the current knowledge of CHIKV genomic organization, cell tropism, and the virus replication cycle, and evaluate the possibility to predict its future evolution. Such understanding may be applied in order to anticipate future epidemics and reduce the incidence by development and application of, for example, vaccination and antiviral therapy.

Replication cycle of chikungunya: A re-emerging arbovirus. Virology. Sep 2 2009

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Whooping cough immunity lasts longer than previously thought

AJCann — Fri, 30 Oct 2009 16:00:26 +0000

The eradication of vaccine-preventable infectious diseases remains an important public health priority. To achieve this goal, the level of immunity afforded needs to be high and long-lasting. For whooping cough (pertussis), one of the leading causes of mortality in infants, immunity has been shown to wane in some individuals. The epidemiological impacts of this observation depend critically on the duration of protective immunity in the entire population, which remains notoriously difficult to estimate. Immunity to whooping cough lasts at least 30 years on average, much longer than previously thought, according to a new study. Once thought to be under control following widespread childhood vaccination, whooping cough has been on the rise since the 1980s in the United States and other countries. Several explanations have been proposed for the surprising increase in cases, and one leading idea is that the immunity enjoyed by vaccinated or previously exposed people is waning. It has been documented that, in some individuals, immunity has waned over time, but details of how long protection typically lasts and how its waning affects disease transmission have not been clear.

To try to answer these questions, researchers used mathematical models to explore various scenarios and compared the predictions generated by those models to data on whooping cough incidence. They constructed two different models based on assumptions of the effects of pertussis exposure on a person whose immunity has lapsed and that person’s relative contribution to transmission. Then they compared the models’ predictions to whooping cough incidence data from England and Wales from both the pre-vaccine era (1945-1957) and the vaccine era (1958-1972). In particular, they looked for matches in two key measures: the number of years between big outbreaks and the frequency of “extinctions” – periods of time when no whooping cough cases were reported in the population.

The analysis revealed that, on average, whooping cough immunity lasts at least 30 years and perhaps as long as 70 years after natural infection. This is surprising because clinical epidemiologists currently believe the duration of pertussis immunity is somewhere between four and 20 years. In addition, repeat infections appear to contribute relatively little to the transmission cycle. And when people whose immunity has waned are re-exposed to whooping cough, they rarely become infected. In fact, their immunity to the disease may be boosted by re-exposure. Still, the researchers are cautious about drawing conclusions about current day vaccination practices from their study of historical data. It is worth pointing out that in the past 20 years or so, the nature of the vaccines that have been used has changed quite fundamentally. The data used in the study are from a time when a whole-cell vaccine was in use; now an acellular vaccine, which stimulates a different part of the immune system, is typically used, especially in North America.

Estimating the Duration of Pertussis Immunity Using Epidemiological Signatures. PLoS Pathog 5(10): e1000647 doi:10.1371/journal.ppat.1000647
Case notifications of pertussis have shown an increase in a number of countries with high rates of routine pediatric immunization. This has led to significant public health concerns over a possible pertussis re-emergence. A leading proposed explanation for the observed increase in incidence is the loss of immunity to pertussis, which is known to occur after both natural infection and vaccination. Little is known, however, about the typical duration of immunity and its epidemiological implications. Here, we analyze a simple mathematical model, exploring specifically the inter-epidemic period and fade-out frequency. These predictions are then contrasted with detailed incidence data for England and Wales. We find model output to be most sensitive to assumptions concerning naturally acquired immunity, which allows us to estimate the average duration of immunity. Our results support a period of natural immunity that is, on average, long-lasting (at least 30 years) but inherently variable.

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Healthcare for insects?

AJCann — Thu, 29 Oct 2009 17:00:28 +0000

Insects are the most abundant and diverse animal class on earth, and they are associated with an amazing variety of symbiotic microorganisms. In fact, mutualistic bacteria probably constitute a key factor for the enormous success of insects in adapting to novel environments and food sources. Several insect taxa completely depend on their mutualistic bacteria for successful growth and reproduction, and the nutrients that are provided by the bacteria have been elucidated in some cases by physiological and/or genomic studies. These nutritional interactions have been the focus of considerable attention, and it is generally assumed that the advantage for the insect in most insect–bacteria symbioses is the supply with nutrients. Recently, however, an increasing number of studies indicate that another type of symbiotic associations can play an equally crucial role: the protection of the insect host or its nutritional resources against pathogens, parasitoids or predators by symbiotic microorganisms. Interestingly, a specific group of bacteria is involved in approximately half of the described defensive symbioses: the high-GC Gram-positive actinobacteria. Why are members of this group so common as defensive mutualists in insects, while they are only very rarely found to be involved in nutritional symbioses? This article argues that actinobacteria are predisposed towards engaging in defensive rather than nutritional interactions owing to their ecological and physiological prerequisites, in particular their ability to exploit a wide range of nutrient sources and their extraordinary potential to produce secondary metabolites with antibiotic properties. A comparison of defensive insect–actinobacteria symbioses known to date yields interesting insights into the conditions under which such associations evolve and points to future directions for research on other insect taxa that might be protected by microorganisms.

Mutualistic microorganisms are well known to play a key role in providing nutrients for successful growth and reproduction in many insects. Several recent studies indicate that they can be equally important for the protection of the host and its nutritional resources against pathogen attack. In particular, different actinobacteria have been found to defend ants, beetles and wasps against detrimental microorganisms by producing antibiotics. The extraordinary abilities of actinobacteria to exploit a wide variety of carbon and nitrogen sources and their extensive repertoire of secondary metabolites probably predispose this group to engage in protective symbioses. Defensive mutualisms with actinobacteria might constitute a general and widespread theme in the ecology and evolution of arthropods, and the study of the secondary metabolites involved promises to uncover novel drug candidates for human medicine.

Actinobacteria as mutualists: general healthcare for insects? Trends Microbiol. Oct 21 2009

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Rethinking dengue hemorrhagic fever

AJCann — Wed, 28 Oct 2009 16:00:47 +0000

Dengue virus infection usually causes a severe flu like illness, although symptoms may be mild in young children. DHF, however, is a severe and sometimes fatal complication of dengue virus infection that affects about half a million people every year after infection with any one of the four dengue virus (DENV) serotypes. DHF patients usually fall into two groups; children and adults who become infected with a second dengue virus serotype after an initial primary dengue virus infection with a different serotype, and infants with primary dengue virus infections born to mothers who have some dengue virus immunity. The widely accepted explanation for the pathogenesis of DHF in these settings, particularly during infancy, is antibody-dependent enhancement (ADE) of DENV infection.

Researchers conducted a prospective nested case-control study of DENV infections during infancy. Clinical data and blood samples were collected from 4,441 mothers and infants in up to two pre-illness study visits, and surveillance was performed for symptomatic and inapparent DENV infections. Pre-illness plasma samples were used to measure the associations between maternally derived anti-DENV3 antibody-neutralizing and enhancing capacities at the time of DENV3 infection and development of infant DHF. The study examined 60 infants with DENV infections across a wide spectrum of disease severity. DENV3 was the predominant serotype among the infants with symptomatic (35/40) and inapparent (15/20) DENV infections, and 59/60 infants had a primary DENV infection. The estimated in vitro anti-DENV3 neutralizing capacity at birth positively correlated with the age of symptomatic primary DENV3 illness in infants. At the time of symptomatic DENV3 infection, essentially all infants had low anti-DENV3 neutralizing activity and measurable DENV3 ADE activity. The infants who developed DHF did not have significantly higher frequencies or levels of DENV3 ADE activity compared to symptomatic infants without DHF. A higher weight-for-age in the first 3 mo of life and at illness presentation was associated with a greater risk for DHF from a primary DENV infection during infancy. This prospective nested case-control study of primarily DENV3 infections during infancy has shown that infants exhibit a full range of disease severity after primary DENV infections.

The current model for development of DHF in infants around 6 months old is that anti-dengue virus antibodies transferred from a dengue-immune mother to her child somehow enhance dengue virus infection, resulting in more severe symptoms (the antibody-dependent enhancement model). These results support an initial in vivo protective role for maternally derived antibody. There was no significant association between DENV3 ADE activity at illness onset and the development of DHF compared with less severe symptomatic illness. The results of this study should encourage rethinking or refinement of the current ADE pathogenesis model for infant DHF and stimulate new directions of research into mechanisms responsible for the development of DHF during infancy.

A Prospective Nested Case-Control Study of Dengue in Infants: Rethinking and Refining the Antibody-Dependent Enhancement Dengue Hemorrhagic Fever Model. PLoS Med 6(10): e1000171 doi:10.1371/journal.pmed.1000171

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