fungal infections acquire drug-resistance

guardian |  “Fungi are everywhere,” said Prof Gordon Brown, head of the Aberdeen mycology centre.

“We breathe in more than 100 spores of aspergillus every day. Normally our immune systems mop them up but, when our disease defences are compromised – for example, during cancer treatments or after traumatic injuries – they lose the ability to fight back. 

“Fungi can spread through patients’ bodies and into their spines and brains. Patients who would otherwise survive treatments are dying every year from such infections.”

This point was also stressed by Prof Neil Gow, another Aberdeen researcher. “Essentially fatal fungal infections are diseases of the diseased,” he said. 

In addition, premature babies and patients with the inherited condition cystic fibrosis are also vulnerable. 

However, the problem is even worse in developing countries. In sub-Saharan nations, where millions are infected with HIV – which causes severe depletion of patients’ immune systems – infections with cryptococcus and pneumocystis fungi account for more than half a million deaths a year.

“The total global number of fungal deaths is about the same as the number of deaths from malaria but the amount that is spent on fungal infection research is only a fraction of the cash that goes on malaria research,” added Gow.

A vaccine that could protect against fungal disease has yet to be developed, while the rise of resistance to the class of medicines known as azole drugs is causing alarm among doctors.

Recent reports from the US and Europe indicate that resistance to azole drugs is increasing in both aspergillus and candida fungi. The widespread use of agricultural fungicides to protect crops and their use in some paints and coatings has been linked to the rise of this resistance.

gnotobiotic: the woes of a germ-free organism

guardian |  Peering inside one of these chambers, I met the eyes of one of the strangest animals on the planet. It looked like just a mouse, and that is precisely why it was so weird. It was just a mouse, and nothing more.

Almost every other animal on Earth, whether centipede or crocodile, flatworm or flamingo, hippo or human, is a teeming mass of bacteria and other microbes. Each of these miniature communities is known as a microbiome. Every human hosts a microbiome consisting of some 39 trillion microbes, roughly one for each of their own cells. Every ant in a colony is a colony itself. Every resident in a zoo is a zoo in its own right. Even the simplest of animals such as sponges, whose static bodies are never more than a few cells thick, are home to thriving microbiomes.

But not the mice in Gordon’s lab. They spend their entire lives separated from the outside world, and from microbes. Their isolators contain everything they need: drinking water, brown nuggets of chow, straw chips for bedding, and a white styrofoam hutch for mating in privacy. Gordon’s team irradiates all of these items to sterilise them before piling them into loading cylinders. They sterilise the cylinders by steaming them at a high temperature and pressure, before hooking them to portholes in the back of the isolators, using connecting sleeves that they also sterilise.

It is laborious work, but it ensures that the mice are born into a world without microbes, and grow up without microbial contact. The term for this is “gnotobiosis”, from the Greek for “known life”. We know exactly what lives in these animals – which is nothing. Unlike every other mouse on the planet, each of these rodents is a mouse and nothing more. An empty vessel. A silhouette, unfilled. An ecosystem of one.

Each isolator had a pair of black rubber gloves affixed to two portholes, through which the researchers could manipulate what was inside. The gloves were thick. When I stuck my hands in, I quickly started sweating.

I awkwardly picked up one of the mice. It sat snugly on my palm, white-furred and pink-eyed. It was a strange feeling: I was holding this animal but only via two black protrusions into its hermetically sealed world. It was sitting on me and yet completely separated from me. When I had shaken hands with Gordon earlier, we had exchanged microbes. When I stroked this mouse, we exchanged nothing.

The mouse seemed normal, but it was not. Growing up without microbes, its gut had not developed properly – it had less surface area for absorbing nutrients, its walls were leakier, it renewed itself at a slower pace, and the blood vessels that supplied it with nutrients were sparse. The rest of its body hadn’t fared much better. Compared with its normal microbe-laden peers, its bones were weaker, its immune system was compromised, and it probably behaved differently too. It was, as microbiologist Theodor Rosebury once wrote, “a miserable creature, seeming at nearly every point to require an artificial substitute for the germs [it] lacks”.