Tuberculosis research for dummies

This is a work in progress article to form an easily understandable starting point for biologists new to TB research. I’m publishing it in incomplete form mainly as a to-do list for myself. The goal is to link to a FEW comprehensive reviews and landmark historical papers because the number of reviews out there is really overwhelming.

This is not for laypersons seeking basic information about TB as a disease, you can easily find that elsewhere.

Anatomy of the bug

In vitro growth characteristics

  • Classical growth media
  • What is the meaning of Rough vs Smooth colonies
  • Approximate doubling times of lab strains
  • Why do we grow it in broth with surfactant, and what are the circumstances where yo shouldn’t
  • What is OADC
  • Decontaminating clinical isolates for culture
  • How is MGIT used in research besides clinical diagnostics
  • Antibiotic resistance genes that can be used for reporter or expression plasmids
  • Transformation of Mtb with plasmids


  • Mycobrowser: database of genes for Mtb H37Rv and a bunch of other reference species/strains
  • The “Rv” numbering system, where does it come from?
  • RD1 and what genes are in it (therefore, which antigens would you NOT expect to see adaptive responses to from BCG-vaccinated-only individuals)
  • What antigens are in PPD
  • What antigens are in Quantiferon

Other differences between Mtb and M.bovis versus non-tuberculous mycobacteria (NTMs)

Common lab strains and where they came from

  • H37Rv vs H47Ra
  • CDC1551
  • Erdman
  • Strains of BCG
  • Strains of smeg

History for nerds

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The Transformer

(As with many other dreams, this takes place in a large building, which is the labyrinth that contains everything in the world.)

I was in a room with white plastic tables and MDF bookshelves, perhaps a meeting room in a library or goverment office. There were several cages filled with shredded paper on some of the shelves and tables, holding baby mammals of various species. I opened one of the cages containing a very small puppy with ginger fur, but young as it was, it attacked me.

“Don’t touch the animals,” warned one of the government officers waiting around with me. “You don’t know what can happen if they bite you.” The bite of a puppy with milk teeth? I wondered.

The mayor arrived at last. He had once been the mayor of New York City but had been sacked from office. Somehow he had found the labyrinth and taken it over. He had an entourage of two or three other men in suits, including a dark-haired, good-looking young one.

One of the officers who had been waiting with me stood up at the front of the room and began speaking. She said that they had (developed? Been given?) a machine that could temporarily transform any mammal into any other species of mammal. What this meant for the city was that it could make huge sums of money by setting up a Contract Research Organisation. But unlike other animal CROs that did toxicology and efficacy studies in rabbits, mice, and dogs, this new CRO could produce data from living human bodies. But since the humans were really just rabbits, mice, and dogs, it would enable them to do incredible experiments that could never be performed on real humans.

She invited the mayor to view a live demonstration of the transformer. One of the other officers took the cage with the ginger puppy, as well as another containing two hooded lab rats. We headed to the main lift lobby and took a lift down, down so the way to one of the lowest floors in the basement. To my surprise, the lobby doors opened on a small theatre with red velvet curtains framing its stage.

A closed booth with a desk and a laptop next to it stood on the stage. To the right of the stage was a pile of empty cages, smelling of various things. One of the officers from the first room mounted the stairs to the left of the stage and headed towards the computer and booth with the puppy. I didn’t see what happened to it, because the mayor’s young assistant suddenly seemed to be in distress.

He held his hands in front of him, bent sharply at the wrist with the fingers together, stiff and straight. He tried to sidle away from the group, but it was impossible not to notice him. As he shook his head, his ears grew large, triangular and floppy, and he grunted repeatedly. The mayor grimaced in disgust. The two other suits, without any other command, stepped up behind the younger man and drew long knives from their jackets. They swung together.

I ran without waiting for the blades to fall. There was a wet thwack and a crack together, the sound I have heard hundreds of times in butcher shops. Shouting. I ran out and through the corridors, around the back of the theatre to where I knew from my years-long inhabitation of the labyrinth that the cargo lifts should be, hoping that the VIPs and bureaucrats would not. Some surprised workers were loading empty plastic crates of the kind live chickens are transported in. I shoved them aside rudely and dived in. I punched the button for the forty-ninth floor over and over, praying for the door to close quickly.

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Hotel level

I had a dream that my sisters and I were hunting for something precious through a labyrinth of hotel rooms. (It’s always a labyrinth.) We kept getting killed. But every time we respawned, the traces of how far we had gotten before were still there. We left signposts and tools for our future lives.
In the last room I remember before waking up, my sisters were cornered on a sofa by a man who was threatening them with a lethal weapon. I was standing off to one side, so I could see that on the wall behind the sofa one of us had scrawled “escape route: ARSON”. And on the side table within reach of their hands, an oil lamp, lit…

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Pegang anjing

I just remembered the weirdest damn thing from my primary school days. A stray dog had puppies at the side of the sports field and I spent a bunch of spare time in class making these elaborate disposable mittens out of exercise book paper and gum, because the school toilet didn’t have soap to wash hands and it was the only way I could think of to be able to pick up the puppies and still be able to touch my lunch box and play with my Muslim friends afterwards.

(My parents had drilled it into us that we had to wash our hands with soap after touching animals before eating and it never occurred to me to take that any way other than literally. As an adult owning an indoor cat an dog both on my bed as I write this, I have relaxed a little on that rule…)

I was like 8 or 9 years old, max. (Because it was in Taiping, and I can timestamp my entire life by location because I’ve never lived anywhere longer than four years.) At that age already got biosafety/must wear PPE mentality. No wonder I work in infectious diseases now.

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This morning I was chatting with a physician from a Francophone country who’s volunteering at a charity clinic while waiting to pass her exams to practice in South Africa. I asked her what health problems she commonly sees among the clients.
“Scabies, allergic rhinitis, achivey…”
“What’s achivey? I haven’t heard of it before.”
“It’s a virus, it can be sexually transmitted, it cause AIDS.”
“Ohhhhhhhh that’s how you pronounce “H”, “I”, “V” in French!”

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Umesh G Lalloo talk

Political instability interrupts treatment, facilitates disease spread e.g. strikes in South Africa, post election violence in Kenya, refugees from Syria.
Paradoxical IRIS-like reactions in HIV-negative TB patients.
Why can we not shorten the course of treatment despite the best drugs?
Why do some people not get sick despite similar exposure?

Focus on TB in HIV patients in South Africa research may be confounding picture of disease in immunocompetent patients.
Ultra short course phase 3 failure- was based on phase 2 results but phase 2 was underpowered.
Primate models may be more relevant than mouse.
Protection vs exposure- he has not gotten TB but several of his colleagues has. Healthcare workers may be a good cohort to study.
Diagnostic solutions: giant pouched rat (he misspoke as mouse)
Worst case scenario: may have to reopen sanatoria in the absence of effective drugs.

INH prophylaxis lead to resistance?
Ans: if you put a huge cohort of HIV positive patients on prophylaxis, the benefit may outweigh the risk.

GeneXpert does not detect INH resistance, is this a problem?

do you know of any plans to introduce UV in South Africa?
Problem is that it requires good engineering to implement effectively- if not, ineffective, UV burns, etc.
However it could help in combination with other measures e.g. masks. Church of Scotland Hospital study.

What is the fundamental problem of TB in South Africa?
It’s behaviour because we have worse TB rates than poorer African countries like Tanzania.
I am using behaviour in a broad sense – we are doing something wrong. Need to discuss with politicians.

What do u think is the “real” number of people latently infected?
There has not been enough evidence eg strong postmortem study to recover AFB from tissue.

Do u think us in Durban and KZN have some difference from rest of country?
Rest of country is not doing so well either! CPT produces a huge number of TB cases.

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Air Liquide

me: Boss asked me to get a quote for CO2 from Air Liquide.
Mr Potato: Why? Aren’t we already using Air Liquide?
me: No, all our gas comes from Afrox.
Mr Potato: But Air Liquide is the gold standard in science.
Mr Potato: Because I had no idea we were using Afrox!

Backstory: We’ve been having trouble growing macrophages and Boss is convinced it’s due to the carbon dioxide supply being contaminated with chemicals from the tanks. (Mammalian cells are usually cultured in air with added 5% carbon dioxide.) Mrs. Boss was tasked with putting together some home-made chemical scrubbers, basically, cylinders filled with activated charcoal, but hasn’t gotten around to it for months. Meanwhile Postdoc and I have not been able to do macrophage experiments because they keep dying…

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Dereliction of predation

Just thinking about mosquito larvae cos I need to email a Plasmodium guy to ask him to be on my academic committee…

Back in Singapore I kept dwarf pufferfish for a while. They’re really cute and funny little fish, smaller than a marble. They’re also quite aggressive going after any live food that piques their interest, like snails. You won’t have a snail problem with these guys. Continue reading

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There are no cats in America

Another guest post by Mr. Potato.

  • It’s 1992 and I am an 8 year old sitting on the floor of my parent’s house in Wisconsin watching a cartoon about a talking mouse immigrating to the US in 1885. Towards the beginning of An American Tail, the anthropomorphic mice sing of their expectations– “There are no cats in America, and the streets are paved with cheese!” For some reason, I never forgot that song.
  • It’s March 2015, a crisp Sunday morning in Durban, South Africa, and I am at church. My attention is wandering when suddenly the words “American politics” jolts me back to the sermon. The pastor is illustrating one of his points using the US political system and specific party platforms as an example. I get it, of course. But so does everyone else because they know American politics as well. What could you say about the political system and parties of, say, Canada? South Africa?
  • Continue reading

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Half way to the best policies on earth: an engineer’s first impressions of South Africa

Mr Potato has been here for a couple of months now; he sent this email to his former colleagues at Aerospace Company That Shall Not Be Named.

I’ve settled into life in South Africa, with all its ups and downs. Power cuts, theft, and language barriers. That’s just life in Africa. The land here is beautiful, and my wife and I agree that, on the whole, South Africa is more beautiful than any other place we have lived. I think only Ireland is as pretty.

This place is pretty screwed up, though, no way around that. South African natives I meet and hang out with openly admit it. When people hear my American accent, they immediately tell me how much they want to move to America (oh, but that’s a topic deserving its own email later) or anywhere else.

One thing I’ve noticed in South Africa are some of the best public/government Procedures (as opposed to Policy or Processes) anywhere I have lived. The US could learn a thing or two about laws, statutes, and regulation. For example, roads in dark and winding areas have LED lights on the sides of the road to make sure you don’t wander off a hill at night. In a land full of diseases I see posters and other encouragement for good sanitation. Anti-HIV drugs are free to anyone. Immigration laws are actually more concise and navigable than the US.

But this place is profoundly dysfunctional! The laws are world class, why is this place a third world country? Continue reading

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