Did you know that guinea pigs cough? I didn’t… but then I’ve never had a pet guinea pig… In fact I’ve discovered that all mammals cough, who knew?! Guinea pigs apparently have a cough pathway (from something stimulating a cough through neural networks and chemical signals to the actual cough) that is the same as humans so they are a great animal model for studying coughs in humans…??

Have the Nuts & Bolts Team finally lost the plot due to Covid-19 and what does this rambling about small furry animals have to do with microbiology I hear you ask? Let’s see where this one goes; we do like to challenge your loyalty to the subject of microbiology!
 
Now for a real leap in my train of thought. Why do patients with tuberculosis (TB) cough? Okay that might seem like an off the wall thought, I have just re-established my TB MDT meeting with the Respiratory Consultants so maybe I can blame them!?  But like me, have you ever wondered why patients cough? No… got better things to be doing? Hmmmmm, maybe it’s just me then….
 
Tuberculosis, caused by the bacterium Mycobacterium tuberculosis (MTB), is probably the most common infection in the World (yep certainly more than pesky Covid-19!). It is estimated that 25% of the World’s population is infected with M. tuberculosis. That’s about 1.75 billion people. Added to that 1.5 million people die every year from TB (as of today World Covid-19 deaths are 946K). TB is in the Top 10 causes of death worldwide, and is the highest death caused by a single microorganism. Whereas globally we are struggling to control and “treat” Covid-19, TB is PREVENTABLE and CURABLE.
 
TB is spread from person-to-person via large droplets, much the same as Covid-19. The reproductive rate (R0) for TB depends on whether the person has latent TB (i.e. the infection is contained by the person’s immune system) or whether the patient is actually coughing out the bacterium. Oh yeah this blog was about coughing!! Latent TB has an R0 of about 0.25-0.5 whereas symptomatic (coughing) TB has an R0 of 4 (every person with “coughing” TB infects 4 other people).
 
So if infection is spread by people coughing, the bacterium MTB needs people to cough in order to spread the infection.
 
So we come back to my original question, why do guinea pigs cough?
 
Historical coughing?
Up until now we thought people with TB coughed because the infection caused inflammation and tissue damage in the lungs leading to the local production of cytokines and other inflammatory molecules. These molecules caused increased production of receptors involved in cough hypersensitivity which then responded to excess mucous and the patient coughed. It turns out this is wrong!
 
A landmark study from Texas, USA, has shown that MTB produces a glycolipid molecule called sulfolipid-1 (SL-1) which makes guinea pigs cough. It turns out that MTB produces a lot of SL-1 as it forms a major component of the bacterium’s cell wall, in fact it makes up 1% of the dry weight of MTB, cool fact!
 
SL-1 has been known about since 1959, and work done in the 1970s showed that SL-1 was a major virulence factor for MTB. But no one had worked out what SL-1 actually did… until now.
 
How did the researchers show SL-1 causes coughing?
The researchers from Texas studied MTB in guinea pigs because, as we now know, guinea pigs cough like humans. First of all the researchers showed that a nebulised extract containing only lipid molecules from TB was sufficient to cause a cough whereas an extract identical in every way except it didn’t contain the lipid molecules didn’t cause a cough (and before you ask I have no idea how you give a guinea pig a nebuliser). So ECIC looks into that and well nebulisers in Guinea pigs… is a thing, I swear ECIC needs to get out more!!

Next the researchers took various modified MTB strains and compared extracts from these with their ability to cause a cough. This showed that MTB strains without the ability to produce SL-1 did not cause coughing.
 
The next step was to show that SL-1 did interact and stimulate nociceptive neurons in vitro (i.e. outside of an animal host) and sure enough SL-1 did stimulate these nerves.
 
The researchers then went back to the guinea pigs and repeated the nebuliser experiment with a pure extract of SL-1 and sure enough SL-1 caused a cough.
 
The final step in the research was to take MTB strains that did not produce SL-1 and see what happened when they infected guinea pigs. It turns out that MTB that doesn’t produce SL-1 still causes the infection TB in exactly the same way as with wild type bacteria BUT in the modified infections the guinea pigs just don’t cough.
 
It turns out that SL-1 actually directly stimulates nociceptive (pain sensing) neurons in lungs which then triggers coughing.
 
So this is a lot of work to show that MTB actually induces coughing in infected guinea pigs, so who cares? Why would MTB “want” to make us cough?
 
If SL-1 actually causes the cough it can help the bacterium spread; it’s manipulating us to further its domination! (A little dramatic maybe but TRUE!!). Guinea pigs have shown that people with TB cough because the bacterium, MTB, tells them to cough! Cool huh?
 
Why would M. tuberculosis have evolved a way of making us cough?
Let’s go back to how MTB spreads from person-to-person. TB is spread via large droplets and the most efficient way for an infected person to produce large droplets is to form them by coughing. So coughing aids the spread of TB. It is therefore most certainly an evolutionary advantage to MTB for its host to cough, and what better way to make sure its host coughs then for the bacterium itself to be responsible for making its host cough.
 
This is exactly what MTB appears to do. It doesn’t rely on its host “reflex” to cough, it “tells” its host to cough by producing the molecule SL-1 which stimulates the host’s nervous system and causes a cough which expels bacteria out of the lungs ready to infect other people!
 
Gosh, Nature is so clever!!
 
So what does this mean for clinical medicine?
For me this is where it gets even more exciting. Can I use the word “exciting”!? If TB is spread by coughing, and we know the molecule SL-1 is responsible for the coughing, then could we produce another molecule that blocks SL-1 and stop the coughing? If we could abolish the coughing whilst treating the patients then we could prevent TB from spreading. This would bring the R0 down well below 1 and maybe one day TB would eventually burn out. We would essentially be saying “MTB you can cause the infection in this person, but you can’t spread to anyone else”. And if we can block droplet spread in this way, can it be applied to other respiratory infections… including pesky Covid-19?
 
Just think about it; a bacterium that has been the scourge of humans for thousands of years, causing billions of cases and millions of deaths, eventually dying out. What an amazing thing that would be?
 
Reference
Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough. C Ruhl, B Pasko, H Khan, et al. Cell, 181; 293-305

One of life’s unsolved mysteries is “how did life on Earth begin?” Did it start here spontaneously as “God created us” or did Darwin get it right with his “evolution theory”? And are we alone in our universe? Let’s skip the God versus Darwin bit and jump straight to the question “did life arrive from outer space” and “can life survive in space?”
 
When times get “trying” here on planet Earth ECIC wishes she was on Pluto with her cats, her rules and no people! But she may not be alone!! The newest research suggests that bacteria can survive in the hostile environment of space; maybe the dream of living on Pluto with remote “homeworking” for a Consultant Microbiologist might be a reality (our hospital computer system is called Enterprise after all!)
 
No, No, No, stick with me!!! It’s true, those pesky microorganisms have been found to survive on the outside of the ISS (International Space Station). There’s even a named theory… the theory that living organisms can survive and transfer through space is known as “panspermia”. 

Editor Chief in Charge and I have spent the weekend trying to work out what we’re going to do if/when we can’t go on holiday later this year because of a certain unmentionable pesky virus. The basic answer is that we might not be going somewhere exotic! But why might not being able to go on holiday somewhere exotic be a good idea?!?
 
I know… pufferfish!
 
Pufferfish are tropical fish found especially in Asia. They are called pufferfish because they have a rather unusual defence strategy; they can fill their stomachs with water so that they balloon up into a ball shooting numerous spiky spines outwards. Any predator stupid enough to try and eat a pufferfish gets a mouth or stomach full of spines and probably chokes… nasty. Bloat, from the Disney film “Finding Nemo” was a pufferfish; he blows up like a beach ball every time something startles him… he’s my favourite character and he’s hilarious!

The Editor-Chief-in-Charge is a curd nerd… she not only loves to eat cheese BUT she also makes her own cheese. There is nothing quite as tasty as homemade cheese but it’s certainly not fast food. In fact it’s a very, very, very slow food. It takes a day to make, a couple of days to press, and months or years to mature…. But it is great fun and it might surprise you to know that it is also a lesson in microbiology. [I wonder if the ECIC will still be a curd nerd after reading this?!]

The government are allowing us to visit the beach but are advising us to stay out of the water as there are no lifeguards on duty and do not want additional casualties in hospital. But there might be another reason for us to consider staying out too! Viruses!!! Really!!? Can you actually find viruses in the sea? It’s a simple question but not one many of us have considered before… including me, but then why would we?
 
You might think that seawater is too salty for viruses and that they would never survive in such a hostile environment. Alternatively you might think that if viruses can survive on surfaces like plastic, metal and cardboard then why not also in the sea. But do we know?
 
Well back in 1990 Scientists confirmed that viruses can indeed be found in seawater; while looking at seawater with transmission electron microscopes (TEM) they saw “something unusual” but they didn’t actually know at that time what it was… however they could see them! So they started to study them. Remember, TEMs can “see” much smaller objects than normal light microscopes; the limit of magnification of a light microscope is about 1,000x, not enough to see a virus, whereas TEMs can magnify 10,000,000x! OK I know you youngsters think 1990 seems a long time ago but in scientific terms it’s not that long, it’s only since these discoveries in the 1990s that they actually confirmed viruses were there, even though “infection” from contaminated seawater was suspected.
 
Further studies have shown that in fact there are lots and lots and lots of viruses in seawater….

There seems to be huge amount of confusion about what tests are available for Covid-19. It doesn’t help that politicians and the media keep using the wrong terms and don’t understand what the different tests tell us. The squabbles seem to surround the numbers delivered rather than correct testing!
 
There are 3 main tests that are currently being discussed:

1. Polymerase Chain Reaction (PCR) commonly referred to as a “molecular test”
2. Antigen (Ag)
3. Antibody (IgM and IgG)

 
In order to understand the value of these tests it is important to understand the basic structure of a virus.
 
The structure of a virus

The Microbiologist picked up the phone to call out a result.
 
“This one looks interesting” he said to himself even though he knew he had been told never to use the word interesting in relation to microbiology…. Ever…!
 
“You have a baby boy on the ward with salmonellosis, what’s the story?” he asked when the Paediatric SHO answered the phone.
 
“He’s a six week old who developed bloody diarrhoea a couple of days ago and started vomiting. He was febrile and looked septic so we started him on empirical IV Ceftriaxone.”
 
“Any pets?” asked the Microbiologist.
 
“He’s only 6 weeks old, why would he have any pets?” answered the tired junior.
 
“Not him, the family; specifically reptiles. Any snakes or lizards?”
 
“I have no idea.”
 
“Well carry on with the IV Ceftriaxone as he has a Salmonella species in his blood culture and call me back about the reptiles… no wait, I’ll come up and ask myself.”
 
The junior doctor hung up. Muttering to himself about mad Microbiologists he wandered off to get on with some other work.
 
So why did the Microbiologist want to know about reptiles? Was he just mad or was there method to his madness?

The Biomedical Scientist walked hesitantly into the duty Microbiologists office.
 
“We have a mould growing in a blood culture” they said.
 
“You mean a yeast?” asked the Microbiologist.
 
“Nope, definitely a mould” replied the BMS.
 
“A contaminant maybe?” asked the Microbiologist again, now starting to hope this was the case.
 
“Nope, definitely not a contaminant” replied the BMS.
 
“Please tell me this was handled in Cat 3?” asked the Microbiologist again, starting to sound worried and thinking he should maybe put the Health and Safety Executive (HSE) telephone number into his phone!
 
“Nope, not in Cat 3” replied the BMS looking crest fallen, “but it should have been… I think it’s Talaromyces marneffei”
 
The Microbiologist just stared at them lost for words… why did it always happen when he was on duty?!
 
What is Talaromyces marneffei?
T. marneffei is a dimorphic fungus; it has two types of growth depending on the temperature (a bit like cheese! Cheese is a solid block when in the fridge but when sliced and put on toast under a grill it’s all gooey!!!) It used to be called Penicillium marneffei, but like many other microorganisms it has undergone a recent name change just to keep us on our toes.