Mining soil for new antibiotics

Methicillin-resistant Staph aureus. Photo NIAID

The beginning of 2015 brought (potentially) good news for medicine: the discovery of a new antibiotic - teixobactin - isolated from soil bacteria. This result was published in Nature on January 22. (Unfortunately the whole text is not visible without payment or subscription.) Many newspapers and news outlets covered the story in early January, for instance the Guardian, and the New York Times. Teixobactin is a small peptide that acts as an inhibitor of cell wall synthesis in Gram-positive bacteria, which means it can kill pathogens like drug-resistant Staphylococcus aureus (often referred to as MRSA, or methicillin-resistant S. aureus).

The issue at stake here is, of course, the increasing prevalence of antibiotic-resistant bacteria worldwide, a situation well summarized in an article at Swissinfo.ch. We have thus seen a dramatic increase in resistant strains of, for instance, S. aureus, Escherichia coli and Klebsiella pneumoniae. Who or what is to blame? Most probably the overuse of antibiotics, not only in humans but also in animals. It is frightening to know that some pathogenic strains can survive our entire arsenal of antibiotics, while new potent drugs are extremely hard to find. Some simple solutions have helped mitigate the problem, notably more effective and systematic hand disinfection by hopital personnel, but this will not prevent all cases of infection. New antimicrobials are clearly needed, but where to find them?

The debate over influenza research is still on

H5N1 virion. Photo Cynthia Goldsmith/Jackie Katz

Two years ago, a controversy emerged about the research on influenza virus H5N1, and the potential risk associated with it. This controversy followed the publication of two research articles in Science and Nature, and I wrote about it in January 2012 in this blog post. Briefly, scientists have used so-called “gain-of-functions” experiments, in which strains of influenza viruses are selected for new traits such as higher transmissibility between ferrets (the preferred animal model in these studies). The objections that were raised by some critics of this research were of two kinds: first, the information available in these papers could be used by terrorists in order to produce bioweapons; second, modified influenza viruses could escape the lab by accident and create a pandemic. The first objection led to a very rare decision in scientific publishing, namely the redaction of the articles to remove potentially sensitive data. The important public concern also led the authors of these studies to promulgate a moratorium on this type of work. After this temporary stop, the experiments started again with additional biosafety measures. 

The debate, however, is far from over. The reason for this? Well, the recent publications of several studies dealing with influenza virus, most notably a paper by Y. Kawaoka (the author of the 2012 Nature publication) on avian influenza viruses related to the 1918 “Spanish flu” virus. This research triggered a heated response from several scientists, which was loudly echoed in the mainstream press (see for instance in the Guardian and in the Independent). In that particular case, it seems that the scientific community is truly divided on the matter. An example of this dissent was the publication of a statement of concern by a group of scientists known as the Cambridge Working Group, which in essence asked for a better assessment of the risks of virus research via the organization of a conference that would deal with all present issues. Such a meeting could resemble the famous Asilomar conference of 1975, where the risks associated with recombinant DNA were debated. Other virologists, however, have fought back these reactions of distrust and have created another group, Scientists for Science, which aims at promoting the benefits of this research, and highlight the fact that serious safety regulations are already in place for virus research. 

Oceans, bacteria, and the quest for new drugs

A marine sponge of the genus Theonella. Photo by Nick Hobgood.

We rely on natural products in medicine: the vast majority of pharmaceutical drugs are thus of plant or microbial origin. (The purely synthetic drugs, which have no counterparts in the environment, are the exception rather than the rule.) To name potent examples of natural products, take antibiotics (discovered in fungi and bacteria), the anti-malaria drug artemisinin (isolated from sweet wormwood) or simply aspirin (salicylic acid is present in willow bark). Many people, I think, forget about this, as they oppose a so-called ‘natural’ medicine to a ‘chemical’ medicine (the pills you get from your doctor). 

It is not easy to find new active compounds, however, and much more difficult to test them and turn them into a real medicine. The situation doesn’t look that good, notably because of the high increase of antibiotic-resistant strains of bacteria, and the paucity of new drugs available. A natural environment that has long been recognized as a promising source of new chemicals is the largest on Earth—oceans—, and many researchers are mining the sea in search of new organisms and their specific biochemical abilities. For instance, the research project PharmaSea, funded by the European Union, was launched in 2013 with the goal of discovering new microbial organisms that could be the source of useful chemicals for medicine or industry. This team of academics and industry researchers plan to explore the deep bottom of the sea, looking for environments that are poorly known and potentially harbor interesting organisms. Here’s an excerpt from the project website:

“Marine organisms that live more than 6,000 meters below the sea level are considered to be an interesting source of novel bioactive compounds as they survive under extreme conditions. "Trenches are separated from each other and represent islands of diversity. They are not connected to each other and life has evolved differently in each one", explains Marcel Jaspars [PharmaSea project leader]. “

PharmaSea is an ambitious project, and it may not be easy at all to get many new products out of it, but the goal has to be praised, as we surely are in need of new biochemicals, particularly new antibiotics.

Should science be apolitical?

Read the other day in the magazine the Atlantic: “The danger of making science political”, by Puneet Opal, medical doctor and professor of neurology at the Northwestern University Feinberg School of Medicine. Opal reflects on the relation between science and politics; he observes that, in the US, science is associated with the Democrat party, and he asks the question: why is it so?

Opal’s article is echoing another piece published recently in Nature, “Science must be seen to bridge the political divide”, by Daniel Sarewitz, from the Consortium for Science, Policy and Outcomes at Arizona State University. Sarewitz complains about a very US-centered situation, that is, the fact that most American scientists seem to side with the Democrats against the Republicans. He takes as an example the letter written by many Nobel laureates in support of Obama’s reelection in 2012. This bias, Sarewitz claims, is a bad thing for science. He writes:

“To prevent science from continuing its worrying slide towards politicization, here’s a New Year’s resolution for scientists, especially in the United States: gain the confidence of people and politicians across the political spectrum by demonstrating that science is bipartisan.”

Scientists keep an eye on a new SARS-like virus

Coronavirus. Electron microscope photo by Phil Murphy/CDC.

In 2003, a coronavirus named SARS (for Severe Acute Respiratory Syndrome) made nine hundreds victims, most of them in Asia. Usually coronaviruses are not dangerous - they cause a cold or stomach flu -, but this one killed one among ten infected human beings. Thanks to the prompt response of the sanitary authorities all over the world, SARS was relatively rapidly controlled.

This year, a SARS-like virus has appeared in Middle East, and scientists and health officers keep a very close eye on it, as Nature News reports. At present it remains unclear whether this new virus could become a real worldwide threat, but it killed five of the nine cases known so far. 
The first cases were reported this Summer in Saudi Arabia and in Qatar, but in November evidence showed that people had been infected by the new virus in Jordan already this Spring.

The comeback of whooping cough

October issue of Microbe, published by ASM.

I read a very interesting—and somewhat alarming—article in the October issue of the journal Microbe (formerly ASM News). In this article, Merry Buckley explains that whooping cough (aka pertussis), a childhood disease that has strongly declined since the introduction of a vaccine in the 1940s, is now on the rise again. We even see epidemics! says Buckley.

In 2012, in the USA, the number of pertussis cases is expected to be the highest in fifty years, approaching 40,000. Other countries such as Australia and the Netherlands also have high incidence of the disease—in the Netherlands, 6,000 cases were reported in 2009, against only 30 cases in 1980. The causes of this comeback are not fully understood, but scientists have gathered many clues.

Whooping cough is caused by Bordetella pertussis, a Gram negative bacterium belonging to the group beta Proteobacteria. It infects the respiratory system, causing a characteristic ‘whoop’ sound in sick children. Teens and adults can also be infected, although the symptoms are milder than in small children. In the prevaccine era, pertussis was a terrible threat, killing on average 5,000 children a year during the 1920s and 30s in the USA alone. At this period, the epidemics peaked following a cyclic pattern of a couple of years.

Are all our modern health issues linked to our microbiome?

June issue of Scientific American

The human microbiome is definitely the sensation of this Summer 2012. [Kind of a Carly Rae Jepsen for science!]

In June alone, our microbial inhabitants were featured on the cover of Scientific American (watch their beautiful infographics), Nature, Science and Microbe…

The Human Microbiome Project (HMP), a $170 million research consortium funded by the US National Institute of Health (NIH), just released two reports in Nature accompanied by fifteen publications in PLoS ONE. The consortium, strong of about 200 researchers, studied the diversity of microbes inhabiting the body (skin, mouth, nose, gut, urogenital tract) of 242 healthy people, using new sequencing technologies to catalog the microbes.

The bottom line? Microbial diversity is very high between healthy individuals. It is therefore impossible to define a typical ‘healthy’ microbiome. In a way, every individual develops his/her own personal set of microbes. The diversity, however, is not totally random and patterns are clearly present in various areas of the body.

What news from the ‘arsenic life’ front?

Mono Lake, CA, photo by NASA

This story has already become sort of a case study. In December 2010, NASA held a press conference about its astrobiology research program and the discovery of a bacterium from Mono Lake (CA) allegedly capable of substituting phosphorus by arsenic in its DNA. The research was published in ScienceExpress and attracted a lot of attention from the media - mostly as a consequence of the ‘hype’ factor brought by NASA, which went as far as saying that “The definition of life has just expanded”. All life on Earth shares the same DNA, whose backbone is made of sugar and phosphate. If any organism could replace phosphate by arsenate, that indeed would be very surprising and exciting.

The controversy over H5N1 research

Ferret, photo by Mika Hiltunen

Since last November, the scientific community has been shaken by what the journal Science has called "a media storm" on H5N1 research. I don't really have an a priori opinion about the potential risks of this research – I am not a virologist, after all – but this is a fascinating controversy which is of importance for microbiologists in general. Science provides us with a special page archiving the news and commentaries related to these events. 

It all started with experiments on H5N1 avian influenza virus that were meant to study what mutations can increase its transmissibility in ferrets (commonly used as a model animal for influenza research). Two virologists in different countries – Ron Fouchier in the Netherlands and Yoshihiro Kawaoka in the USA/Japan – have managed to create H5N1 strains that are transmissible between ferrets (and thus, potentially, between human beings) and want to publish their independent results in Science (Fouchier) and Nature (Kawaoka). The question that these researchers are willing to answer is: can H5N1 cause a human pandemia, and if yes, what mutations would allow it to do so? Fouchier argues, for instance, that knowing the mutations will allow the researchers to look for them in the field, thus being proactive against the virus spread.