MicrobiologyBytes

Globalization and the trend toward the integration of trade of crops and livestock could have a major impact on the emergence and dissemination of pathogens. Shifts in agricultural practice result in opportunities for pathogens to expand into new host species and to spread rapidly to new territories. For example, the epidemics of bovine spongiform encephalitis (BSE) and the foot and mouth disease epidemic were caused by changing agricultural practices providing new opportunities for transmission, including the use of meat and bone meal in cattle feed, and the long-distance transport of livestock, respectively. The broiler poultry industry has been transformed within the last 50 years from a market dominated by smallholder chicken farms to a multibillion dollar industry controlled by a handful of multinational companies who supply a limited number of breeding lines to a global market. Infectious diseases of chicken flocks are a major economic burden on the industry. In particular, Staphylococcus aureus is associated with several infections of poultry including septic arthritis, subdermal abscesses (“bumble foot”), and gangrenous dermatitis. The impact of globalization on the emergence and spread of pathogens is an important veterinary and public health issue. S. aureus is a notorious human pathogen associated with serious nosocomial and community-acquired infections. In addition, S. aureus is a major cause of animal diseases including skeletal infections of poultry, which are a large economic burden on the global broiler chicken industry.

This new article provides evidence that the majority of S. aureus isolates from broiler chickens are the descendants of a single human-to-poultry host jump that occurred approximately 38 years ago (range, 30 to 63 years ago) by a subtype of the worldwide human ST5 clonal lineage unique to Poland. In contrast to human subtypes of the ST5 radiation, which demonstrate strong geographic clustering, the poultry ST5 clade was distributed in different continents, consistent with wide dissemination via the global poultry industry distribution network. The poultry ST5 clade has undergone genetic diversification from its human progenitor strain by acquisition of novel mobile genetic elements from an avian-specific accessory gene pool, and by the inactivation of several proteins important for human disease pathogenesis. These genetic events have resulted in enhanced resistance to killing by chicken heterophils, reflecting avian host-adaptive evolution.

This work shows the evolutionary history of a major new animal pathogen that has undergone rapid avian host adaptation and intercontinental dissemination. These data provide a new paradigm for the impact of human activities on the emergence of animal pathogens.

Recent human-to-poultry host jump, adaptation, and pandemic spread of Staphylococcus aureus. PNAS USA November 2, 2009. doi: 10.1073/pnas.0909285106

Related:

• Evolution and pathogenesis of Staphylococcus aureus
• Staphylococcus aureus: superbug
• Is that chicken bugged?

Dengue fever is a major public health problem in many tropical regions of the world. It is a vector-borne disease, transmitted most often by the mosquito Aedes aegypti. According to the WHO, the prevalence of dengue is highest in tropical areas of Asia and the Americas, with 50-100 million estimated cases of dengue fever and 250,000-500,000 cases of dengue hemorrhagic fever occurring annually worldwide as explosive outbreaks in urban areas.

In Brazil, three dengue virus serotypes (DENV) have been introduced in the past three decades. In 2007-2008, a dengue fever epidemic in Rio de Janeiro led to 240 deaths registered (100 deaths due to dengue hemorrhagic fever and 140 due to other dengue-related complications). This populous city presents highly favorable conditions for transmission of dengue. Dengue surveillance and control in large urban areas with high levels of dengue transmission pose important challenges. Therefore, consistent knowledge of the dynamics of this disease that integrates epidemiological and entomological data is essential.

Human movement is a key factor of dengue virus inflow in Rio de Janeiro, Brazil. The results published in a new paper, based on data from a severe epidemic in 2007-2008, contribute to new understanding on the dynamics of dengue fever in the second largest city in Brazil. This research combines data on dengue fever seroprevalence, recent dengue infection, and vector density in three neighborhoods of Rio de Janeiro: an urban, a suburban, and a slum area. Serological surveys were conducted before and during the epidemic period. Entomological surveys consisted of weekly collections of A. aegypti eggs and adults from traps. This integrated entomological-serological survey showed evidence of silent transmission even during a severe epidemic. No association was observed between household infestation index and risk of dengue infection in these areas, raising new questions about where transmission occurs – in the household, at work or elsewhere. When combined, the neighborhood-specific seroprevalence maps correlated significantly higher risk with areas of intense people traffic. These results add to previous epidemiological studies of dengue virus infections and contribute to the understanding of A. aegypti habits. The conclusions may provide a basis for new studies that could further identify the higher seroprevalence risk areas and help to develop and implement dengue-control programs.

Spatial Evaluation and Modeling of Dengue Seroprevalence and Vector Density in Rio de Janeiro, Brazil. PLoS Negl Trop Dis 3(11): e545. doi:10.1371/journal.pntd.0000545
Rio de Janeiro, Brazil, experienced a severe dengue fever epidemic in 2008. This was the worst epidemic ever, characterized by a sharp increase in case-fatality rate, mainly among younger individuals. A combination of factors, such as climate, mosquito abundance, buildup of the susceptible population, or viral evolution, could explain the severity of this epidemic. The main objective of this study is to model the spatial patterns of dengue seroprevalence in three neighborhoods with different socioeconomic profiles in Rio de Janeiro. As blood sampling coincided with the peak of dengue transmission, we were also able to identify recent dengue infections and visually relate them to Aedes aegypti spatial distribution abundance. We analyzed individual and spatial factors associated with seroprevalence using Generalized Additive Model (GAM). Three neighborhoods were investigated: a central urban neighborhood, and two isolated areas characterized as a slum and a suburban area. Weekly mosquito collections started in September 2006 and continued until March 2008. In each study area, 40 adult traps and 40 egg traps were installed in a random sample of premises, and two infestation indexes calculated: mean adult density and mean egg density. Sera from individuals living in the three neighborhoods were collected before the 2008 epidemic (July through November 2007) and during the epidemic (February through April 2008). Sera were tested for DENV-reactive IgM, IgG, Nested RT-PCR, and Real Time RT-PCR. From the before– after epidemics paired data, we described seroprevalence, recent dengue infections (asymptomatic or not), and seroconversion. Recent dengue infection varied from 1.3% to 14.1% among study areas. The highest IgM seropositivity occurred in the slum, where mosquito abundance was the lowest, but household conditions were the best for promoting contact between hosts and vectors. By fitting spatial GAM we found dengue seroprevalence hotspots located at the entrances of the two isolated communities, which are commercial activity areas with high human movement. No association between recent dengue infection and household’s high mosquito abundance was observed in this sample. This study contributes to better understanding the dynamics of dengue in Rio de Janeiro by assessing the relationship between dengue seroprevalence, recent dengue infection, and vector density. In conclusion, the variation in spatial seroprevalence patterns inside the neighborhoods, with significantly higher risk patches close to the areas with large human movement, suggests that humans may be responsible for virus inflow to small neighborhoods in Rio de Janeiro. Surveillance guidelines should be further discussed, considering these findings, particularly the spatial patterns for both human and mosquito populations.

Related:

• Dengue Virus
• Rethinking dengue hemorrhagic fever
• Pathogenic Flaviviruses

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

Related:

• Plant viruses: master explorers of evolutionary space. Curr Opin Genet Dev. 1993 3(6): 873-877
• Experimental evolution of plant RNA viruses. Heredity. 2008 100(5): 478-483
• Resistance to Plant Viruses

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.

Related:

• Campylobacter jejuni

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

Related:

• Unique cell division machinery in the Archaea
• Getting bacteria into shape
• Cell shape and cell-wall organization in Gram-negative bacteria
• Peptidoglycan – the strength and weakness of bacteria

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.

Related:

• Polyomavirus and Human Merkel Cell Carcinoma
• High prevalence of infection with three new human polyomaviruses
• Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections

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

Related:

• Metabolism, cell growth and the bacterial cell cycle
• How smart are bacteria?

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

Related:

• Chikungunya, an epidemic arbovirosis
• Changing patterns of chikungunya virus
• Chikungunya pandemic reaches Europe