MicrobiologyBytes

Scientists have just challenged the notion that airborne prions are innocuous. It is known that prions can be transmitted through contaminated surgical instruments and, more rarely, through blood transfusions. However, prions are not generally considered to be airborne – in contrast to many viruses such as influenza and chicken pox. In the new study, the authors housed immunodeficient and immunocompetent mice in special inhalation chambers and exposed them to prion-containing aerosols, which induced disease. Exposure to aerosols for one minute was sufficient to induce disease in 100% of mice. The longer the exposure, the shorter the incubation time in the recipient mice, after which they developed the clinical signs of a prion disease. These findings indicate that prions are not airborne. Prions appeared to transfer from the airways and colonize the brain directly, since various immune system defects – known from previous experiments to prevent the passage of prions from the gut to the brain – did not prevent infection.

The prion is the infectious agent that caused the epidemic of “mad cow” disease, also termed bovine spongiform encephalopathy (BSE). BSE claimed the life of more than 280,000 cows in the past decades. Transmission of BSE to humans, e.g. by ingestion of food derived from BSE-infected cows, causes variant Creutzfeldt-Jakob disease which is characterized by a progressive and invariably lethal breakdown of brain cells. Consumption of food made from BSE-infected cows has caused the deaths of almost 300 people. The precautionary measures against prion infections in scientific laboratories, abattoirs, and animal feed factories have not typically included stringent protection against aerosols. These new findings suggest that it may be advisable to consider the possibility of airborne prion transmission, and to create regulations aimed at minimizing the prion infection risks to humans and animals.

Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice. (2011) PLoS Pathog 7(1): e1001257. doi:10.1371/journal.ppat.1001257
Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrPC, efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrPC selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrPSc and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.

Related:

• Researchers find new piece of BSE puzzle
• Oral transmission of prions is enhanced by binding to soil
• New forms of bovine spongiform encephalopathy

Traditionally, research in bacterial communication and co-operation has been performed at the molecular level and less attention has been paid to evolutionary and ecological factors which govern such actions. But Steve Diggle and Roman Popat ask in this article in Microbiology Today, what is the relevance of social evolution for microbes?

Most of us at some point have had the rather unpleasant experience of putting our fingers down a plug-hole only to pull up a slimy goo. As microbiologists are now well aware, this is a large mass of microbial cells that we commonly refer to as a biofilm, and such microbial communities can be found almost everywhere. They are the pioneers of rocky shores which help enable seaweed to settle on rocks. They cause problems in industrial settings such as contamination of beer lines. Clinically, they are of huge importance, contributing to infection, colonization of medical devices and antibiotic resistance. Biofilms consist of numerous cells, often belonging to a number of diverse species surrounded by a complex exopolysaccharide matrix. They remind us that bacterial cells interact with each other and inevitably lead social lives. Recently, there has been a growing interest in studying aspects of sociality using bacteria or other microbial study systems.

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Enteric bacteria such as Escherichia coli swim by rotating a set of flagella that forms a bundle when the flagellar motors turn in the counterclockwise (CCW) direction The bundle falls apart when one or more motors turns in the clockwise (CW) direction, and the bacterium tumbles. A new swimming direction is selected upon resuming the CCW rotation of the flagellar motors. By modulating the CCW and CW intervals according to external chemical cues, the cells are able to migrate toward attractants or away from repellents.

This paper report observations of motility patterns of marine bacterium Vibrio alginolyticus. The authors fround found that the bacteria employ a unique cyclic three-step (forward–reverse–flick) swimming pattern for chemotaxis; they regulate both forward and backward swimming times according to a given chemical profile. By employing the three-step chemotactic strategy, cells of V. alginolyticus are able to focus on a point source of attractant rapidly and form a compact swarm around it. This is apparently a significant niche for V. alginolyticus, which live in ocean where nutrients are scarce and rapidly dispersed by currents.

Bacterial flagellum as a propeller and as a rudder for efficient chemotaxis. PNAS USA 4th January 4 2011 doi: 10.1073/pnas.1011953108
We investigate swimming and chemotactic behaviors of the polarly flagellated marine bacteria Vibrio alginolyticus in an aqueous medium. Our observations show that V. alginolyticus execute a cyclic, three-step (forward, reverse, and flick) swimming pattern that is distinctively different from the run–tumble pattern adopted by Escherichia coli. Specifically, the bacterium backtracks its forward swimming path when the motor reverses. However, upon resuming forward swimming, the flagellum flicks and a new swimming direction is selected at random. In a chemically homogeneous medium (no attractant or repellent), the consecutive forward tf and backward tb swimming times are uncorrelated. Interestingly, although tf and tb are not distributed in a Poissonian fashion, their difference Δt = |tf – tb| is. Near a point source of attractant, on the other hand, tf and tb are found to be strongly correlated, and Δt obeys a bimodal distribution. These observations indicate that V. alginolyticus exploit the time-reversal symmetry of forward and backward swimming by using the time difference to regulate their chemotactic behavior. By adopting the three-step cycle, cells of V. alginolyticus are able to quickly respond to a chemical gradient as well as to localize near a point source of attractant.

Related:

• Bacterial Motility

A large fraction of the world’s most widespread and problematic pathogens, such as the influenza virus, seem to persist in nature by evading host immune responses by inducing immunity to genetically and phenotypically plastic epitopes (aka antigenic variation). The more recent re-emergence of pandemic influenza A/H1N1 and avian H5N1 viruses has called attention to the urgent need for more effective influenza vaccines. Developing such vaccines will require more than just moving from an egg-based to a tissue-culture–based manufacturing process. It will also require a new conceptual understanding of pathogen–host interactions, as well as new approaches and technologies to circumvent immune evasion by pathogens capable of more genetic variation. This paper discusses these challenges, focusing on some potentially fruitful directions for future research.

Vaccines often take between 16 and 20 years to develop, and the challenge now is to understand deceptive imprinting better and to systematically identify and characterize deceptive epitopes and low-efficiency, interfering epitopes in influenza and other viruses. Progress would enable targeting of both immunodominant deceptive epitopes and low-efficiency epitopes for genetic modification. In addition, more studies are needed to determine whether such genetic modifications can actually lead to significantly greater vaccine efficacy, but there is great promise in these understanding-driven approaches.

How Can Vaccines Against Influenza and Other Viral Diseases Be Made More Effective? 2010 PLoS Biol 8(12): e1000571. doi:10.1371/journal.pbio.1000571

Related:

• The 2009 H1N1 pandemic – what went right and what went wrong?
• RNA replicons – a new approach to influenza virus vaccines
• Protective immunity against influenza

Most of us know how it feels to have an upset stomach. In this article in Microbiology Today Ian Poxton informs us how the enormous number of microbes that live in our gut usually get on very well together, living in relative harmony with one another, but disturb the balance and …

The gastrointestinal tract contains one of the most complex and diverse ecosystems found on the planet. The micro-organisms (microbiota: mainly bacteria) inhabiting this harsh and varying environment have to cope with physical and chemical extremes, as well as the host’s immune defences. Bacteria inhabiting the gut must enter via the mouth. They traverse the acidic stomach, and then travel through the small intestine where exposure to the powerful detergent actions of bile and destructive enzymes are maximal and flow rate is high. Oxygen becomes increasingly limiting, and by the time the large intestine is reached the conditions are extremely anaerobic and many toxic metabolites are produced there. However, the microbiota should not be considered a constantly flowing stream of micro-organisms that will be ultimately all eliminated in faeces: many are adherent, and even those free in the lumen have a division rate that exceeds the flow rate, so reaching a steady state that prevents their wash through.

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The recent discovery of miRNAs of viral origin has dramatically changed our view on virus-host interaction. Viral miRNAs have been shown to regulate genes of both cellular and viral origin, contributing to a favorable environment for the virus. However, the real importance of virus-encoded miRNAs during infection of their hosts remains elusive. This paper reports the first functional phenotype of a miRNA knock-out mutant of the mouse cytomegalovirus in vivo. It shows that the mutant virus is attenuated specifically in the salivary glands of infected mice, an organ essential for long-term persistence of the virus and host-to-host spread. This attenuation revealed a striking dependence on genetic background of the mice under study. Only combined depletion of natural killer and T cells abolished the phenotype. These results indicate that, by regulating the immune system, viral miRNAs may play an important role in an efficient persistent infection.

Cytomegalovirus microRNAs Facilitate Persistent Virus Infection in Salivary Glands. (2010) PLoS Pathog 6(10): e1001150. doi:10.1371/journal.ppat.1001150
Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets’ messenger RNAs through both translational inhibition and regulation of target RNA stability. Recently, a number of viruses, particularly of the herpesvirus family, have been shown to express their own miRNAs to control both viral and cellular transcripts. Although some targets of viral miRNAs are known, their function in a physiologically relevant infection remains to be elucidated. As such, no in vivo phenotype of a viral miRNA knock-out mutant has been described so far. Here, we report on the first functional phenotype of a miRNA knock-out virus in vivo. During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission. This phenotype depends on several parameters including viral load and mouse genetic background, and is abolished by combined but not single depletion of natural killer (NK) and CD4+ T cells. Together, our results point towards a miRNA-based immunoevasion mechanism important for long-term virus persistence.

Related:

• Cytomegalovirus immune manipulation
• Human Cytomegalovirus-encoded microRNA regulates expression of multiple genes involved in replication
• Human cytomegalovirus and the cell cycle