Short articles


As the saying goes, if it sounds too good to be true then it probably is. So when the BBC announced last week that “predatory bacteria can wipe out superbugs” I felt somewhat sceptical. The article suggested that Bdellovibrio bacteriovorus could help ease fears of an antibiotic apocalypse by “devouring” the insides of bacteria that are resistant to multiple drugs. The paper in question, less excitingly titled “Injections of predatory bacteria work alongside host immune cells to treat Shigella infection in zebrafish larvae”, is much more cautiously realistic about its ability to cure the world of superbugs any time soon.

Bdellovibrio is a small, motile bacterium that hunts other bacteria, attaching to their surface before entering and forming a structure known as a bdelloplast. Four hours later, the infected cell bursts open and releases the Bdellovibrio harboured inside, allowing them to attack other cells. It is this predatory behaviour that the researchers suggest could be harnessed and used to treat infections that are resistant to all other lines of treatment.

The scientists found that introducing Bdellovibrio into zebrafish larvae in isolation had no adverse effect on the survival rate of the host. When they added a normally-lethal amount of drug-resistant Shigella to the mix they found that intriguingly, the Bdellovibrio seemed to assist the zebrafish immune system in clearing the pathogen. They believe it worked by reducing the number of Shigella to the point where the immune system could take over and clear the rest. The Bdellovibrio was also targeted after a longer period of time, seemingly producing no ill-effects of its own.

The biology behind Bdellovibrio is a very interesting one and serves neatly to highlight the quirks that you can find once you start digging a bit. The issue here is that, contrary to the BBC news report, it is extraordinarily unlikely to ever become a viable therapeutic option. First, it is hard to believe that patients would find the thought of receiving a dose of bacteria at the large quantity described in the paper a pleasant one. Second, no one would argue against the point that zebrafish and humans are not the most similar. Third, the test subject, Shigella, is not perhaps the most well-known of all multidrug-resistant bacteria and therein lies a flaw in the claims. That being said, the science behind predatory bacteria is fascinating and if it is making some kind of headline news then that can only be a good thing.

Source – Injections of predatory bacteria work alongside host immune cells to treat Shigella infection in zebrafish larvae. Willis et al. 2016. Current Biology.

With thanks to the Thomas lab for useful discussion.


Human African trypanosomiasis (HAT), more commonly known as sleeping sickness, is a disease caused by the protozoan parasite Trypanosoma and spread by its host, the tsetse fly. Endemic in 36 sub-Saharan African countries, HAT causes fever, headaches, joint pain and, once the parasite has crossed the blood-brain barrier, the characteristic sleep cycle disturbances that give the condition its colloquial name.

Developing drugs to combat sleeping sickness and nagana, its equivalent in cattle, is a complex and frequently unsuccessful process. The drugs that are available currently to treat HAT are limited by a risk of toxicity and are not always effective. The hope is that new therapeutic targets could be found by identifying essential components of the parasite, including its metabolism.

Amino acid uptake is hugely important for trypanosomes. Blood is the sole diet of the tsetse and therefore the parasite must be able to survive on amino acids as their energy source when they are in this stage of their life cycle. They are also auxotrophic for a number of amino acids, meaning they cannot produce them themselves. The transporters for these therefore provide a potential drug target; block the ability to uptake essential metabolites and the parasite will die.

A paper published in early January describes two transporters that could become potential therapeutic targets. Mathieu et al. looked at two amino acids, arginine and lysine, that are essential for trypanosome survival. They transformed these into Saccharomyces cerevisiae mutants and found that they enabled growth on lysine and arginine in strains of S. cerevisiae that would otherwise have been unable to grow.

The team then used transport assays to reveal that these transporters have both high affinity and selectivity for their substrates, then assessed the essentiality of these proteins by down-regulating their expression through RNA interference and found that growth of these parasites was significantly reduced.

These transporters are therefore interesting therapeutic candidates because of the reliance of the trypanosome on them for survival. Importantly, these are not related to uptake systems in humans and so any drug that worked against them would not run the risk of off-target effects.

For the full article, visit Transporting Science.

Source – Arginine and lysine transporters are essential for Trypanosoma brucei, Mathieu et al. (2017), PLOS ONE



Computational biology may provide the key to curing neglected tropical diseases. The parasitic worm Schistosoma mansoni appears to have lost the ability to uptake glucose through two of its four transporters, raising the possibility that the functional ones could be a promising target of new drugs to treat the disease it causes, schistosomiasis.

Schistosomes are trematode parasites that transmitted to humans through contaminated water sources. Their intermediate hosts, freshwater snails, release larval parasites that bury through the skin to establish infection. Over 60 million people were estimated to have received treatment for schistosomiasis in 2014, a disease widespread across Africa, the Middle East and South America.

Schistosome infection is controlled largely through improving sanitation and targeting the snail hosts. With the number of people infected annually still very high it is however desirable to find a new treatment option that might have fewer side effects than the pre-existing option, praziquantel. As the only drug available to treat schistosomiasis there is also concern about the risk of resistance to praziquantel developing.

Designing drugs against parasites is considerably trickier than for their bacterial counterparts – as eukaryotes they share a lot of their cellular machinery with humans, meaning any drug that targets these may also have effects on the patient. It is therefore important to exploit all differences between parasites and humans to maximise the probability of developing a successful candidate.

A paper published in BMC Genomics is a good example of this. The team led by Alejandro Cabezas-Cruz and James Valdes investigated four glucose transporters encoded by the schistosome genome, SGTP1-4. Glucose is a particularly interesting molecule in schistosome metabolism because the parasite switches to glycolysis from oxidative phosphorylation after infection in the presence of glucose. It was thought therefore that if a drug could block uptake of glucose then this switch could not occur and result in morbidity for the parasite.

The team found that two of these transporters, SGTP2 and 3, were relatively similar to human glucose transporters whereas SGTP1 and 4 were Platyhelminthes(worm)-specific. SGTP2 and 3 appeared to have lost the ability to transport glucose whereas the worm-specific ones were still functional. That the schistosomes have essential glucose transporters that are unlike human ones is greatly promising for the developing of a drug against them; blocking them should be lethal to the parasite without affecting mammalian cells.

With advances in high-throughput screening and computational biology it is likely that more such targets will be revealed in the near future. It now remains to be seen whether these candidates will be followed up on given the lack of financial incentive in the parasitic disease market.

Source – Cabezas-Cruz et al. (2015). Fast evolutionary rates associated with functional loss in class I glucose transporters of Schistosoma mansoni. BMC Genomics, 16:980.



An ABC transporter in Leishmania potentially confers resistance to the antimony used in leishmanicidal drugs by sequestering the compound in vesicles and exporting them via the parasite’s flagellar pocket.

Leishmaniasis is a neglected tropical disease (NTD) caused by the protozoan parasite Leishmania. It is responsible for 20 000 – 30 000 deaths every year in countries including India, Bangladesh and South Sudan. The World Health Organisation (WHO) estimates that 310 million are at risk of developing visceral leishmaniasis.

Leishmania has two distinct life cycles, one in its mammalian host and one in its sandfly vector.  The sandfly injects promastigotes into the skin during a blood meal. These promastigotes are then taken up by macrophages where they transform into amastigotes and multiply. They are eventually released from the infected cell into the bloodstream from where they may be taken up by another sandfly during its next blood meal.

Current treatments for leishmaniasis, including amphotericin B, miltefosine and pentavalent antimonials, can be both toxic and expensive. This coupled with the ever-increasing issue of drug resistance means that the disease is in danger of reaching crisis point. Scientists have been attempting to elucidate the various ways in which resistance could arise in the hope of curtailing some of the problems facing Leishmania control.

A team from Spain have done just that, identifying an ATP-binding cassette (ABC) transporter in Leishmania which they believe might be involved in resistance to antimony. Leishmania has 42 ABC genes yet few have been characterised. The team led by Ana Perea looked at SbV, an antimony-based drug which is taken up by the amastigote (intracellular) form of the parasite. It becomes reduced to SbIII and activated once inside the macrophages. Leishmania encodes enzymes that are capable of reducing SbV to SbIII, which then combines with thiols that are effluxed from the parasite.

The transporter in question is LABCG2. It was chosen as related transporters LABCG4 and LABCG6 had previously been implicated in resistance to the drug miltefosine. LABCG2 is involved in phosphatidylserine (PS) externalisation during infection of the host macrophages. They found that overexpressing LABCG2 resulting in the promastigotes becoming 7-fold more resistant to the antimony-based compound. This resistance was however not seen in other leishmanicidal drugs such as miltefosine.

The team then delved into exactly what was behind the resistance to SbIII. The parasites were incubated in antimony and after 60 minutes the accumulation of the compound was measured. The mutants which overexpressed LABCG2 were found to have accumulated 76% of the total amount of SbIII that the controls had. They interpreted this as an indication that the LABCG2 transporter mediates the elimination of antimony from the parasite.

Finally, they looked to establish whether thiols, which bind to and export heavy metals, could play a role in Leishmania antimony resistance. They found that thiol efflux from the parasites was greater in the presence of antimony and, following tagging by green fluorescent protein (GFP) discovered that the transporter does localise at the plasma membrane.

Overexpressing the LABCG2 ABC transporter might therefore protect Leishmania against otherwise toxic antimonic drugs by effluxing them as a complex bound to thiols. They believe that this could be a mechanism by which Leishmania may become drug resistant, although emphasise the need for LABCG2 knockout mutants to really establish what role the transporter plays in the parasite.

Source – Perea et al. (2016). The LABCG2 transporter from the protozoan parasite Leishmania is involved in antimony resistance. Antimicrobial Agents and Chemotherapy, 60, 3489 – 3496.



A transporter has been linked to the survival of the parasite that causes Chagas disease in Latin America.

Chagas disease is caused by infection of Trypanosoma cruzi and affects approximately 6 million people worldwide. The parasite spends part of its life cycle in its insect vector and part in the bloodstream of its mammalian host. During this time it is exposed to a variety of different metabolites at various concentrations. The trypanosome has adapted to this and chooses to scavenge these nutrients rather than make them itself.

One group of compounds that the parasite scavenges are polyamines, responsible for cell growth. T. cruzi is auxotrophic for polyamines, meaning it is unable to synthesise them itself. It therefore relies on taking up polyamines from its environment to survive. A team of scientists from Argentina have now found a transporter, TcPAT12, which they think is responsible for this and have linked it to drug resistance.

The team made trypanosome mutants which overexpressed TcPAT12 then grew them in low and high concentrations of polyamines. They found that these mutants took up a much greater concentration of putrescine and spermidine compared to normal (wild-type) parasites, confirming that TcPAT12 is a putrescine/spermidine transporter.

They then grew these mutants in solutions which would cause stress; hydrogen peroxide and two trypanocidal drugs nifurtimox and benznidazole. The mutants fared much better, surviving at greater concentrations of the toxins than the wild-type parasites. Bioinformatics analysis suggests that there could be examples of polyamine transporters in other parasite species too, including Trypanosoma brucei, causative agent of African trypanosomiasis or sleeping sickness, and Leishmania major, which causes leishmaniasis in North Africa and the Middle East.

The team concluded that this TcPAT12 transporter could be a way by which trypanosomes may become resistant to drug treatment. Overexpressing TcPAT12, and subsequently increasing their internal concentration of polyamines, could produce a protective effect against the oxidative stress caused by the trypanocidal drugs. This is therefore something to be mindful of during a time when drug resistance is an increasingly urgent problem.

 Source: Reigada et al. (2016). J Membrane Biol. Trypanosoma cruzi polyamine transporter: its role on parasite growth and survival under stress conditions.



A team of scientists from the Charles University, Prague, have discovered a living organism that appears to be missing a component thought to be essential for life, surviving instead on something taken from bacteria. The components in question are the mitochondria. These are the so-called powerhouses of eukaryotic cells are responsible for making all of the energy for the organism.

Mitochondria were acquired way back in evolutionary time by a process called endosymbiosis, where an ancient ancestor of eukaryotes engulfed a bacterium that somehow managed to survive. This was more successful than those without this bacterium and so it stuck around, eventually becoming the eukaryotic mitochondria. It must have therefore come as quick a shock when Anna Karnkowska’s team discovered a microbe that appeared to manage just fine without mitochondria, a finding which has the potential to really shake up widely accepted evolutionary ideas.

The scientists looked into the DNA of this microbe, Monocercomonoides, and found no genes associated with the presence of mitochondria, including a lack of ones to build it. They believe that it manages to get around the need for this component by acquiring a second system from bacteria in their surroundings. This sulfur mobilisation (SUF) system allows Monocercomonoides to form Fe-S clusters, something that the mitochondria normally assist with. The team believe that the SUF system does a good enough job to make mitochondria dispensable.

So what does this mean for our view on how life evolved? This discovery emphasises the need to continuously question accepted ‘facts’ in science. It also raises the exciting possibility that there are other microbes that have also jettisoned seemingly essential components, highlighting the fluid nature of evolution.

Source: Kamkowska et al., 2016. Current Biology. A eukaryote without a mitochondrial organelle.



‘Putting your face on’ just got a whole lot more literal. Scientists from Massachusetts have developed a new way to turn back the years and make your skin look younger, and it is a bit different to the usual make ups and moisturisers. They have engineered a product called Second Skin and it does exactly what it says on the tin.

As we age, collagen and elastin break down and our skin starts to lose elasticity, leading to the wrinkles and drooping associated with the elderly. This process is accelerated by sun exposure. There is a huge demand for anti-aging creams that promise to increase the collagen within the skin to reduce wrinkles but there are doubts as to how well these actually work. Regardless, the market for such products was valued at approximately $250 billion in 2012 and such a lucrative field is bound to attract the attention of innovators and scientists.

It has been reported in Nature that a new approach has been developed that involved physically layering a new, invisible, ‘skin’ on top of problematic areas. The application works in two steps – a cream made of a form of silicon is first applied before a second, a platinum catalyst, it spread over the top. The catalyst crosslinks the silicon which causes a reflectiveness of the skin surface that is usually found in more youthful complexions.

How does it work? The group claim that this second skin ‘mimics the mechanical properties of natural skin, with respect to elastic recoil, flexibility…’. They say it is comfortably wearable over a period of 24 hours, as well as being moisturising and well tolerated. It has been tested on a double-blind, randomised study in comparison to a placebo and was found to reduce bags under the eyes and wrinkles.

So, could this be the anti-aging revolution? Potentially. Extending the wearability to longer than a single day is surely a must, and it is not yet clear how the product would react against skin disorders such as psoriasis. It is definitely something to keep an eye on though for those keen to keep the years off.

Source –Yu et al. (2016). Nature. An elastic second skin



Dengue who? Dengue is another virus wreaking havoc across the tropics but it isn’t grabbing headlines in the same way that malaria and Zika do. Yet it might be the key to bringing mosquito-borne diseases under control.

Symptoms of dengue infection include fever, headaches and vomiting and can in extreme cases develop in fatal dengue haemorrhagic fever. Dengue fever affects an estimated 100 million people worldwide each year yet it isn’t nearly as well publicised as other diseases, possibly due to a limited effect on Western communities.

However, research into dengue might help us hit the jackpot in the hunt for ways to bring Zika under control. Both viruses are transmitted by the mosquito Aedes aegypti. Researchers have infected this mosquito with a species of bacteria called Wolbachia, and it is this which may hold the key to defeating dengue, Zika and the like.

Wolbachia is a symbiont, which means it will not cause disease to its insect host. When introduced into the mosquito, Wolbachia reduces its ability to transmit dengue virus.

A project has launched in Australia to harness this effect of Wolbachia. Called ‘Eliminate Dengue’, the programme involves releasing mosquitos that contain Wolbachia with the aim of reducing disease spread.

What makes this project brilliant is the involvement of the communities affected by the virus – so called ‘mozzie boxes’ are distributed to willing residents of Cairns and Townsville, who only need to add water and food to the mosquito eggs and wait for them to hatch in a cool, shaded place.

Even school children are getting involved. These ‘Wolbachia Warriors’ are also growing Wolbachia-infected mosquitos.

So what about Zika? As they are transmitted by the same species of mosquito, there‘s no reason why this technique can’t be applied to Zika. The Eliminate Dengue programme is now being rolled out across more densely populated areas like Indonesia, but all initial signs are promising. So it could be goodbye Zika soon if Wolbachia comes up trumps.

For more information, visit



Once bitten, twice shy? Anxious people may overgeneralise experiences in a way that non-anxious people do not.

A study by Rony Paz at the Weizmann Institute of Science investigated how volunteers with generalised anxiety disorder (GAD), a chronic condition characterised by anxiety about a range of issues, would react to a stimulus that had previously been associated with a stressful situation.

Each participant received a sum of money and sounds were played to them as they either gained or lost from their pot. When the sounds were played again later, anxious people were less able to distinguish the ones they had heard before from unfamiliar ones.

This suggests that people with GAD may perceive the world differently to non-anxious people, leaving them less able to copy with stressful situations. Researchers hope that this study may help to develop new therapies to treat anxiety; challenging the altered perceptions first might increase responsiveness to treatment.

Source – New Scientist. 6th April 2016.