mBiosphere

The Anthrax Attacks: Good for Research? Not Really.

The anthrax attacks that took the lives of five people and infected seventeen others took place ten years ago. What are the repurcussions of the events in the Fall of 2001 for science? That’s the question Mike Imperiale of the University of Michigan and Arturo Casadevall of the Albert Einstein College of Medicine seek to address with their new Opinion piece in mBio this week. They say the overall effect of the attacks has been a mixed bag.

On the plus side, say Imperiale and Casadevall, the extra dollars that concern about bioterrorism preparedness has brought to biology research have been welcome at a time when federal funding of biology research overall has declined. But beyond this benefit, the news has mostly been pretty bleak: the added regulatory burden of heightening security has slowed research and increased the expense of studying select agents such as anthrax, discouraged new talent from entering the field, and resulted in the destruction of several microbial collections while preventing the development of new ones.

If you’re involved in research on select agents, has the research climate changed for you since the anthrax attacks? Have the changes helped improve your work or do they detract from it? Use the comments function to let us know.

Commentary: Q Fever Bacterium Needs a Room. Any Room.

A Commentary in mBio this week discusses how new findings on Coxiella burnetii, the causative agent of Q fever, paves the way for future progress in understanding this zoonotic disease.

First discovered in Australia, Q fever is most often contracted from cattle, goats and sheep or from infected meat and milk products. C. burnetii is an unusual intracellular pathogen: it is the only bacterium known to replicate within a vacuole that resembles a phagolysosome. (Note: the phagolysosome is kind of a killing room. It’s a combination of a phagosome, a compartment for killing and digesting pathogens, and a lysosome, an organelle containing enzymes for breaking down wastes and other materials. And yet C. burnetii not only survives in these compartments, it replicates.)

Recent finding show that the Dot/Icm Type 4 Secretion System (T4SS) is necessary for the bacterium to be able to renovate a lysosome into a mature Coxiella-containing vacuole.

In a study in the July/August issue of mBio, researchers proved that when C. burnetii lacks this T4SS, it isn’t picky about what kind of vacuole it inhabits. Beare et al. got the pathogen to replicate in a different kind of vacuole entirely: one that was created by the protozoan parasite Leishmania amazonensis.

The authors of this week’s Commentary say this says something important about how C. burnetii uses T4SS to take advantage of human cells. The cohort of Dot/Icm effector proteins are not the necessary aspect of T4SS, but rather the collective action of those effector proteins, which creates the phagolysosome. In other words, C. burnetii needs a home within human or animal cells, and anything resembling a phagolysosome will do. Advances in genetic analyses will help move studies of the Dot/Icm effector functions forward to figure out more about how the Coxiella-containing vacuole is created.

Antibiotic resistance is ruining our best drugs. Can antivirulence drugs save the day?

Antivirulence drugs disarm pathogens rather than kill them, and although they could be effective in theory, antivirulence drugs have never been tested in humans. A new study to in mBio this week reveals these drugs have the potential to fight infection while avoiding the pitfalls of drug resistance.

Traditional antibiotics aim to kill or stop the growth of pathogens, but antivirulence drugs prevent disease by neutralizing virulence factors, the specific proteins or toxins that a pathogen uses to establish an infection. It’s long been thought that such a strategy could prevent pathogens from developing drug resistance, since antivirulence drugs don’t kill the pathogens that are susceptible and leave a wide opening for the few resistant organisms that may be left. Thus, in theory, antivirulence drugs don’t offer much benefit to the resistant pathogens that get around the drug. However, these ideas have never been tested.

This new study provides evidence that antivirulence drugs have the potential to suppress resistance – if they are applied in the right way. Researchers from Oregon State University carried out laboratory simulations to determine the effect antivirulence drug-resistant strains could have on therapy. They found that in pathogens that rely on cell-to-cell communication and cooperation, resistant strains will not overtake sensitive strains, allowing antivirulence therapies that target social interactions to work even when resistance arises.

“It’s a very important demonstration of the principle that social effects can slow or even halt the spread of resistance to antivirulence drugs,” says Sam Brown, of Edinburgh University, Invited Editor on the study. “Their results align with our understanding of social evolution.”

Mellbye and Schuster created a microcosm that simulates an infection, says Brown, and they used bacteria that employ quorum sensing, a form of communication that enables the bacteria to time their attack for greatest effect. Quorum sensing is an important target for antivirulence drugs because many bacterial pathogens, including the lung pathogen Pseudomonas aeruginosa, employ quorum sensing to control the manufacture of their virulence factors.

To circumvent the problem of creating a strain that is resistant to an antivirulence drug, Brown says, the authors used surrogates. “It’s kind of a role-playing exercise,” to test their ideas, he says. “They used bacteria that behave as we expect drug-resistant bacteria might behave.” “Sensitive” mimics are bacteria that lack the ability to communicate and cooperate. “Resistant” mimics are actually run-of-the-mill bacteria that retain the ability to “talk” amongst themselves.

The researchers pitted resistant mimics against sensitive mimics to test whether resistant strains can proliferate in an infection. The results showed that sensitive mimics cheat to get ahead: they exploit the resources that the resistant bacteria provide through quorum sensing. This delays the growth of all the bacteria, suggesting that resistance to an antivirulence drug that targets quorum sensing would not spread. The authors say this highlights the potential of antivirulence strategies that target cooperative behaviors and shared virulence factors.

Brown is optimistic but circumspect about the findings. “These results could very well stand, but in the the real world resistance could still emerge and we need to be cautious.”

“I think these drugs are promising, even if we do anticipate resistance, because they can slow the rate of resistance evolution, much slower than the rate of resistance evolution to traditional antibiotics,” says Brown.

New genomes show off the abilities of ocean cyanobacterium

The cyanobacterium Cyanothece is a resident of the open ocean, where it fixes nitrogen and carries out photosynthesis. But five new genome sequences reveal that Cyanothece is equipped for a lot more than just plain-old nitrogen fixation. It has versatile metabolic pathways – an asset that makes it a good candidate for light-driven biofuels production.

Raw sewage: home to millions of undescribed viruses

It may hardly seem like news, but here’s the latest: raw sewage is loaded with viruses. That’s the part you may have already guessed. The more astounding aspect of a study published in mBio this week is the diversity those viruses represent. Biologists have described only a few thousand different viruses so far, but this latest study reveals that raw sewage is home to the most diverse array of viruses ever found. Apparently, a vast world of unseen viral diversity exists right under our noses.

Viruses are everywhere: every moment of every day, humans are exposed to viruses on surfaces, in foods, and in water. However, our knowledge of the viral universe is limited to a tiny fraction of those that likely exist. A quick calculation bears this out: there are roughly 1.8 million species of organisms on planet Earth, and each one is host to untold numbers of unique viruses, but only about 3,000 have been identified to date.

To explore this diversity and to better gauge the numbers of unknown viruses that are out there, the researchers applied a metagenomics approach to raw sewage samples from North America, Europe, and Africa. (Unfortunately, in my mind, they lumped the results from these three locations together. How do sewage viruses in Addis Ababa differ from those in Pittsburg?) Cantalupo et al. concentrated and purified the virions in their samples, then isolated DNA and RNA and reverse transcribed it. Deep sequencing resulted in a total of 897,647 high-quality reads (approximately 278 Megabases), which were compared to databases by a series of BLAST searches.

The authors detected signatures from 234 known viruses that represent 26 different “families”, or types, of viruses. Known viruses included human pathogens like Human papillomavirus and norovirus. Also present were several viruses belonging to those familiar denizens of sewers everywhere: rodents and cockroaches. Bacteria are also plentiful in sewage, so it was not surprising that the viruses that prey on bacteria dominated the known genetic signatures. Finally, a large number of the known viruses found in raw sewage came from plants, probably owing to the fact that humans eat plants and plant viruses outnumber other types of viruses in human stool.

Raw sewage contains more mysteries than answers, however: the vast majority of viral genetic signatures belong to unknown viruses. This fact is significant, says the study’s editor, Michael Imperiale of the University of Michigan. Unknown viruses like those found in sewage probably play many roles in human health and environmental processes that we simply do not appreciate yet, he says.

Of the unknown sewage viruses that come from humans, some of them may be opportunists that lie in wait for the human host’s immune system to break down and provide an opening, he says.

Other viruses may be benign or even helpful. “There’s a theory out there that we may be infected with viruses that don’t cause any disease and may have beneficial effects,” says Imperiale. There are examples of animal viruses that bear this out, he says, including a herpes virus in mice that makes them somewhat resistant to bacterial infections.

The study’s authors plan to follow up their examination of sewage viruses with studies of other environments around the world where viruses are likely to thrive.

Michael Imperiale expects more discoveries to come. “I think this is going to be the tip of the iceberg of how many viruses are out there,” he says. “I think the ocean is going to top raw sewage by orders of magnitude,” although they won’t be found in such densities as they are in sewage, he concedes.

[The study's lead author is James Pipas of the University of Pittsburgh. Coauthors are affiliated with Pitt, the University of Barcelona, and Washington University in St. Louis.]