The Bug Blog has been on holiday; okay you know this because there have been no blogs for 4 weeks or so. Having finally finished the 3rd Edition of “Nuts & Bolts” we went on holiday to Costa Rica to see what wildlife we could see; although Costa Rica only represents 0.03% of the World’s land mass it contains 6% of its biodiversity!

​We were really lucky. We saw all sorts of creatures from coatis and kinkajous (possibly the cutest animal ever!) to red-eyed tree frogs, massive cane toads, scarlet macaws and even the resplendent quetzal.

One of the critters you see all over Costa Rica, in fact all over tropical America, is the Leafcutter ant. Leafcutter ants are a curious species of ant. They are seen forming long lines across the rainforest floor carrying oversized pieces of vegetation on their backs. Leafcutter ants form large, complex societies in underground nests more than 30m across, with smaller radiating mounds extending out to a radius of 80m. A whole nest complex can cover up to 600m2 and contain eight million individual ants! But what does this all have to do with Microbiology I hear you ask?

​Well the particular Leafcutter ants at La Selva Biological Station, a protected area of rainforest dedicated to research and study of this special ecosystem, and a place I went on a guided walk with a ranger, has studied these ants and found some new microbiology! La Selva is a special (and very wet) place in Sarapiqui, Costa Rica.

But back to the ants…
Leafcutter ants don’t actually eat the leaves they collect, they are farmers. They use the leaves to produce compost; they use the compost to “feed” and grow a fungus which they then eat. Did you know there are 47 different species of Leafcutter ant and all eat fungi from the Lepiotaceae family (each species of ant eats a slightly different type of fungus)? OK so what has this fungus got to do with clinical microbiology…honest it’s explained a little later! …
 
In order for the ants to farm and grow fungi successfully, it is really important they do not bring back bits of leaf accidentally “contaminated” with a different fungus which might damage their crop. This is especially true if the leaf is contaminated with the fungi Escovopsis spp., which lives and feeds on other fungi! The ants therefore need some way of cleaning the leaves and preventing this contamination from happening. In order to protect their crop the Leafcutter ants are symbiotically colonised with a Pseudonocardia spp. bacterium. This bacterium produces an antifungal which kills the Escovopsis spp., how cool is that!? This previously unknown antifungal was discovered at La Selva in Costa Rica and they called it Selvamicin...
 
Apparently the researchers collected the Pseudonocardia spp. bacterium from two adjacent nests of Leafcutter ants and “screened them” for antimicrobial compounds. Fascinating, I would love to know how they did this… how on earth do you swab a leafcutter ant? I can imagine having to chase it around the laboratory without accidentally squishing it with the swab, or maybe they have a “swab trap” like a camera trap…? Who knows??  
 
Does this have any clinical relevance?
Yes! Selvamicin is a polyene antifungal, similar to Amphotericin B and Nystatin which we already use in clinical microbiology. Selvamicin has been shown to be active against Candida spp., Saccharomyces spp. and Aspergillus fumigatus. I presume it has no activity against the Lepiotaceae spp. which the ants are trying to grow; as clearly that would be a poor evolutionary step!
 
Although Selvamicin is a polyene antifungal, it is different to Amphotericin B and Nystatin in some important areas, especially it’s mechanism of action and its water solubility.
 
Mechanism of Action
So far we don’t yet know how Selvamicin works; we do know it is different to the currently used polyenes. Whereas Amphotericin B and Nystatin interact with ergosterol in the fungal cell membrane, essentially behaving like a detergent by making holes in the membrane, Selvamicin does not. This is important because it means Selvamicin won’t be affected by mechanisms that lead to resistance through changes in ergosterol synthesis.
 
Water solubility
Neither Amphotericin B nor Nystatin is available orally because of their poor solubility; this means they cannot be absorbed from the gut. Selvamicin however has a 300-fold better solubility; so it probably will be orally bioavailable. This could be a game changer because currently only the azole antifungals are available orally. Therefore at the moment, if a patient has an azole resistant infection, they would have to be admitted for intravenous treatment as no other oral agent is available; a second class of oral antifungal would be brilliant.
 
And another thing…
Something slightly peculiar that the researchers at La Selva observed with Selvamicin is that in one of the Leafcutter ant nests the genes for producing Selvamicin were part of the chromosome of the Pseudonocardia spp. whereas in the other nest the genes were in a plasmid (mobile genetic element). The fact that the gene is found in both a chromosome and a plasmid suggests to me that it is part of a mobile genetic element that can move between bacteria. New genes can be added to either chromosomes or plasmids through the action of transposons which are genetic sequences that “help” small segments of genes move between larger sequences of genes. It also implies that Selvamicin production wasn’t originally part of Pseudonocardia spp. genetics and that it has been acquired from somewhere else.
 
So if it was not part of the original genetics where did it come from? Are there other, as of yet, untapped resource of antimicrobials out there in the jungle? I think I need a sabbatical to go and play in the rainforest, I mean “undertake some serious important research” … of course!

In the meantime, before I get approval for my sabbatical, the 3rd edition of Microbiology Nuts and Bolts should be available 2nd April, both on Amazon and now through normal bookshops as well. If you have recently purchased a 2nd edition we will be making any important changes and new content available online, as we did when we released the 2nd edition. We recognise how frustrating it can be to purchase a book just before a new edition is released. In fact this is one of the main reasons we are still self-publishing, because Elsevier would have published the book but they specifically said we couldn’t release free updates and so we had to say no to their offer. But that’s okay; MNB3 is coming… watch this space!

NB Thanks to the Editor Chief in Charge (aka my wife) for her tremendous efforts to get MNB to its 3rd edition…

The mother was frantic.
 
“I don’t know what happened” she cried to the Paediatrician, “he was just a bit irritable when I put him to sleep last night and had a bit of redness around his mouth, but this morning his skin is falling off!” She then dissolved into floods of tears.
 
The Paediatrician took one look at the blisters and broken skin around the baby’s umbilicus and nappy area and asked “could he have been scalded with hot water at all? He looks burnt!

“Can I discuss an unwell baby?” asked the Neonatal Registrar.
 
“Of course, what’s the story?” replied the Microbiologist.
 
“We have a baby who is just over 24 hours old. They were born at term in good condition but started to grunt and looked mottled by 4 hours. We brought them to the Neonatal Unit, did blood cultures and started IV Benzylpenicillin and Gentamicin as per guidelines but they’re not really improving. Do you think we need to change the antibiotics? Has anything grown in the blood culture?”
 
The Microbiologist chose to ignore the last question as blood cultures are incubated in an automated incubator which scans the bottles every 10 minutes. If the blood culture where positive then it would have been phoned already.
 
“Is the baby’s mother okay? Have there been any problems during the pregnancy. Was the mother fully vaccinated? Was the labour normal? Is there anything else you’ve noticed about the baby, any odd lumps, bumps or spots?” asked the Microbiologist.

Maggots are fly larvae. Their life cycle goes like this: flies are attracted to food and other rubbish on which they lay their eggs; later the eggs hatch into maggots, which turn into flies. You may be wondering if you have eaten that picnic sandwich which a fly had just landed on (and possibly laid its eggs), whether the eggs and maggots can survive!? Answer: larvae that might be accidentally ingested with food cannot usually survive in the gastrointestinal environment.

Hospital acquired infections are never a good thing, usually there is simply lapse in care, resources or common sense behind most occurrence. The normal kinds of infection you “expect” to see being acquired in hospitals are MRSA, Norovirus or Clostridium difficile. However sometimes outbreaks can be a real mystery to solve. I have had to deal with an unusual outbreak of hospital acquired fungal infection myself, so I was intrigued to “read on” when I saw this week’s headlines that “a strange outbreak had occurred in a Scottish hospital”.
 
This outbreak occurred at the Queen Elizabeth University Hospital in Glasgow and sadly patients have died as a result. An outbreak is defined when there are two or more cases linked in time, place or person. A single infection can constitute an outbreak if the infection is significantly rare or unlikely in the particular situation. The Glasgow outbreak is unusual in that it is not the normal kind of infection you expect to see being acquired in hospitals, this was cryptococcosis.
 
Cryptococcosis is a fungal infection caused by yeast like organisms of the family Cryptococcus spp. There are three main subspecies which infect humans:

• Cryptococcus neoformans var. neoformans
• Cryptococcus neoformans var. grubii
• Cryptococcus gatii

 
Cryptococcus spp. are found worldwide and throughout the environment; C. gatii is mainly found in the tropics whereas C. neoformans is more common and widespread. C. neoformans is principally found in pigeon droppings and pigeon nests as well as soil whereas C. gatii tends to be found in the bark of trees as well as soil. Other animals have been known to carry Cryptococcus spp. including cats, dogs, horses and even camels, llamas and alpacas!

Okay, so the Bug Blog is usually about the clinical and scientific aspects of microbiology but this week I’m going to do something a bit different. Now I’m not someone who watches much TV; there was very little on that interested me over the Christmas period. However, I did watch a short TV hospital dramatization called Charité on Netflix which I thought was brilliant and something that anyone interested in microbiology would also enjoy. OK so it’s in German with English subtitles, but it is the best show I have watched in a long time! Let me explain.

As some of you will be aware from reading previous New Year blogs (see Pandemic Legacy blog) I love board games and of course microbiology. This year Santa has brought me another brilliant bug board game combo… Plague Inc.
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This is the opposite to the Pandemic games in which humans battle to eradicate bugs; here you are the bug and the aim is to infect cities of the world and kill off entire countries and continents! Now I feel this game lacks the shear panic that Pandemic Legacy gave me but it has meant I have slept over the two weeks of Christmas, which I did not when playing Pandemic Legacy (the ultimate, epic, scary and brilliant game for Microbiologists and all those interested in infection).

But back to Plague Inc, you start as a bacterium (all bacilli of various colours) with one country that you already infect and 5 Trait Cards. You gain DNA points (1 bonus point each round plus 1 for each country where your infection cubes are in control) that allow you to evolve by buying a trait from the Trait Cards you hold in your hand… At the start your bacterium has little potency (2 DNA points) so the game feels a bit slow, but it will grow on you!

​The Microbiologist was sat at his desk Boxing Day morning authorising out results and waiting for some further work on the blood cultures before ringing them out when his oncall mobile phone went off.
 
“Hi, it’s the ED Registrar here; can I discuss a patient with you?”
 
“Of course, what have you got” answered the Microbiologist.
 
“We’ve got a chap who has recently been abroad and has presented with a fever and feeling unwell. The basic story is that he returned home from work in the early hours of this morning looking flushed and tired. His wife was worried about him, as his belly was rather distended, so persuaded him to come to the hospital. He insists this is how he normally feels at this time of year but his wife isn’t convinced.”

Sometimes you come across a patient who represents the perfect storm of allergies, resistance and contra-indications to antimicrobials that really make you scratch your head to come up with a way of treating them. I’m not complaining! These are the kind of clinical conundrums that stretch the brain cells and make Microbiologists earn their money

I was recently doing a ward round on the Critical Care Unit when a Doctor from overseas who was observing on the ward starting asking questions about how we give antibiotics in the UK and why we don’t use continuous infusions. This was a really good discussion, especially as we have recently been thinking about if we should be implementing this method of antibiotic administration locally.