Mycobacterium tuberculosis, sometimes shortened to “MTB”, is a major global pathogen dating back to ancient times, and Yersinia pestis’s best friend. Tuberculosis is currently among the three leading pathogens along with malaria and HIV, and the world’s top infectious killer, according to the WHO. Each year, 10 million people contract the disease and 1.5 million succumb to it, most of them in developping countries. It is estimated that one quarter of the world’s population have been infected. 1. Malnutrition, co-infection with COVID or HIV are major aggravating factors of the disease 2.
Antibiotic-resistant strains of MTB have also become a problem 2, especially because of MTB being a slow-growing mycobacterium. As a mycobacterium, Tuberculosis has a acid-fast and alcohol-resistant cell wall, that’s very rich in lipids, many of which are mycobacterial-exclusive. This peculiar structure acts as a physical barrier and helps mycobacteria preserve their cells from antibiotics 3. Moreover, mycobacteria grow very slowly. Tuberculosis’s doubling time (the time required for a single division) is of 24h). His slow metabolism makes it harder for antibiotics targetting such processes to remain stable long enough to provide a benefit to patients 4. The main course of treatment is usually a cocktail of antibiotics, which needs to be followed for a minimum of 6 months, if not years 5. Failure to follow treatment to the end in turn favours emergence of resistant strains 6.
Slow growth also makes mycobacteria inconvenient microbes to culture, and MTB, a tricky one to diagnose 7. The TB disease can be active (symptomatic) or, more frequently, latent (asymptomatic) in patients, which is why diagnosis is so important.
In the bacterial world, he is easily among the most famous mycobacterium, though only by word of mouth, as he seldom ever meets other people (as his “Tuberculosis” self). Tuberculosis is an odd one out among bacterial pathogens, because of his confessed feelings of attachment and pity towards humans.
He owns Secretion Systems unique to mycobacteria, the ESX Type 7 Secretion Systems. Tuberculosis also acts as the “eldest” of many “twin brothers”, forming the Mycobacterium tuberculosis complex.
Background
Despite being one of the youngest mycobacteria 8, Tuberculosis may be quite old as a bacterial pathogen 9. It has been brought to light recently that he’s probably spent his early life in the Horn of Africa 10,11. Early on, Tuberculosis was an energetic fellow, and very enthusiastic about his pathogenic power. An expert of mammalian immune systems, he had a knack for battling them, especially that of humans. At some point, along with his twin brothers, he started taking care of a shy Yersinia pseudotuberculosis strain to whom he’d made a strong impression (they might’ve met in a mammal’s gut). The two of them were very different already, but it didn’t stop Tuberculosis from teaching this rod everything he knew. Soon enough, the two of them had formed a special bond. As this bacillus turned into Yersinia pestis, Tuberculosis cheered him on and looked after him. Their relationship reached their peak during the plague of Justinian, one of Pestis’s first notable feats.
But, quickly, Tuberculosis realised just how much Pestis had changed in such a “short” amount of time. Indeed, Pestis’d gone from a timid, insecure boy, to an agressive, apathetic mass-killer. Having gathered all bacteria’s attention as a formidable pathogen, he’d developped a strong disdain for humans, and started encouraging others to kill as many of them as they could. This newfound contempt left Tuberculosis contemplative. To him, killing humans was a game that Pestis was taking too far, and it made him realise how much he valued the human cultures and civilisations he’d come to know. During the Black Plague, Tuberculosis asked Pestis to rethink his views on humans. Seeing his friend and mentor taking humanity’s defense greatly angered Pestis, and the talk ended in him brutalising Tuberculosis in a fit of rage. This left Tuberculosis with a damaged eye.
Despite an immediate apology and deep-seated regrets, Pestis and Tuberculosis’s relationship was never the same. Tuberculosis started treasuring humans as living beings, thus growing uneasy with his nature as an obligate pathogen. Though still Pestis’s confident, and famous as such in the bacterial world, his stance on humans clearly made him stand out. Realising that he’d be forever stuck in his pathogenic evolutionary niche, Tuberculosis let himself slip into melancholy, and started living in guilt and self-hatred. Fighting the immune system went from a hobby to necessary for survival. This didn’t stop him from marveling at human progress, especially after being identified by them. As antibiotics gained ground, Pestis found himself remaining sensitive to them. He begged Tuberculosis to take onto his legacy of human massacres, if he were to go extinct. Though saddened for Pestis, Tuberculosis made a point of not endorsing his ways.
Personality
Idealism is what’s eating away at Tuberculosis. At first glance, he appears a laconic, emotionally-stunted young man, clearly lacking joie de vivre. Deep down, he is very empathetic and sensitive. Tuberculosis’s dream world would be one where no such conflict between pathogens, other prokaryotes, and humans exist. As he came to value humanity as individuals, rather than simply as a species, he developed deep-seated self-esteem issues. Tuberculosis is very insecure, and views himself as an innately horrible person, as he got stuck in his evolutionary niche as an obligate pathogen. He hates himself for his way of life, knowing that it doesn’t make him any better than Pestis, and that there’s nothing he can do about it – no matter what he actually thinks. Overall, he could be described as suffering from depression.
As his sensu stricto self, he lives a rather solitary life, fighting for survival against the immune systems of the bodies he inhabits. Tuberculosis is used to living in enemy territory constantly; this is why he’s always wary of his immediate surroundings. As a complex, though, he does have a few relationships, that he developped mostly in his other hosts. But they take great effort on his part to maintain, as he has a tendency to remain on his own.
Mycobacterium tuberculosis complex
Thus far, this page related the experiences of MTB sensu stricto : the human-exclusive TB bacillus. But Tuberculosis shares a consciousness with several other strains, forming the Mycobacterium tuberculosis complex (MTBC). All members of the complex are near (often up to >99% 12, 13) identical on a genomic level 14, 15. These strains are so exceptionally close, they usually share all memories, though their outlooks on life may differ. They are like different incarnations of the same individual. All MTBC members cause tuberculosis, but often in different hosts. Biology-wise, this translates to each of these strains having a unique transcriptomic signature 9. They may be designated as biovars, or subspecies, of MTB. Their phylogeny is still being investigated 16.
The complex is made up of :
- M. tuberculosis sensu stricto (human-exclusive TB)
- M. africanum (human-exclusive TB)
- M. bovis (human, bovine TB)
- M. caprae (caprine TB)
- M. microti (rodent TB)
- M. pinipedii (seal TB)
- M. canettii (suspected ancestor of the complex 14)
- M. mungi
- M. orygis
- M. suricattae
- … and probably more strains yet to be identified 17, 18.
Unlike other complexed bacteria, the MTBC prefer keeping others in the dark about their actual nature, referring to other members as “mere” twin brothers. As such, it isn’t shocking to outsiders for complex members to know about each other’s memories, or sharing thoughts and gut feelings, as it’s pretty common among bacterial species with high-identity genomic content. The difference lies is that bacterial “twins” retain an individuality of their own: they remain unaware of what the other is thinking, feeling… a majority of the time. That is not true of complexed bacteria.
Despite him acting as the most mature one, it should be noted MTB sensu stricto is probably not the earliest of these personas to have emerged.
Mycobacterium bovis
Bovis is one of the closest existing avatars to Tuberculosis sensu stricto. His experience as Bacillus Calmette-Guérin revived some of his inner joy, making him the merriest strain of the MTBC.
Relationships
Deinococcus radiodurans
On paper, it would seem like the both of them have what it takes to get along. But Tuberculosis doesn’t like how simplistic Radiodurans’s proposed vision of the world comes off as (he is unaware it’s the intended purpose). Radiodurans’s optimism does not seem to reach him, also.
Homo sapiens
Tuberculosis recognises that humanity is not a monolith, and how complex it can be; he knows that it shouldn’t be taken as a whole. He often pities his hosts. He is fascinated by human creative potential, and enjoys learning about folklore, authors, illustrators, musicians, and any other kinds of artists.
Lactobacillus casei
Tuberculosis once befriended Casei as Bovis. Casei being the outcast that he was, he noticed Bovis didn’t want to blend in either, and so he took interest in him every time he was to be encountered in milk. Though he doesn’t show it, Tuberculosis is very jealous of Casei; not so much for his fame, but more so to be able to be used so widely as a probiotic. As Bovis, though, he does sincerely enjoy his company, it’s very soothing to him.
Other Mycobacteria
Mycobacterium avium complex
Avium is Tuberculosis’s brother. In the past, Tuberculosis mocked Avium for being so deeply mannered, and for refusing to venture deeper into the respiratory tractus.
Mycobacterium leprae
big rework of leprae going on so
Yersinia pestis
It is thought that zoonotic transmission from cattle to man was a route of tuberculosis during the Neolithic period – though has been heavily debated and it may not as played a role in the emergence of human TB, as was previously inferred. Early Earlier MTBC strains and Y. pseudotuberculosis strains could have met in the mammalian gut 14,19, 20, 21.
The relationship between Tuberculosis and Pestis can be complex to describe on both ends. Overall, they share a mentor-mentee-like dynamic, with Pestis now being on par with his mentor as a pathogen. Though they don’t see each other very often anymore, their bond remains the strongest they share with anyone.
Tuberculosis holds immense affection for Pestis. Despite enduring emotional abuse from Pestis in the past, and having witnessed his infectious feats, deep down, Tuberculosis still sees him in the same light as when they met : a lost youngster in need of guidance. In their younger years, Tuberculosis taught Pestis everything he knew about mammalian immune systems. He holds himself accountable for how cruel and relentless Pestis turned out to be. As a mentor, he thinks it should’ve been his responsibility to tell Pestis off before it was too late, which feeds into his guilt and self-hatred.
Curiously, Pestis, despite belonging to the Yersinia pseudotuberculosis complex himself, doesn’t seem to see through the MTB complex.
Trivia
- Like most other mycobacteria, Tuberculosis has a cord factor (trehalose dimycolate), which his scarf and coat are made of.
- Also typical of Mycobacterium, Tuberculosis has noticeably smaller ears than other bacteria. But he’s the only one to be ashamed of them, and prefers hiding them behind hair as much as possible.
- He enjoys naps.
- The model M. tuberculosis strain used in labs worldwide is M. tuberculosis H37Rv.
- Even outside of humans and their cultures, he does appreciate all of his hosts.
- Though he is an obligate aerobe, meaning he needs oxygen to survive, oxygen is scarce in his immediate environment during infection. This is why he’s evolved mechanisms to survive prolonged hypoxia 22.
References
Additional
Tuberculosis’s wikidoc page does a very good job of introducing the physiological and immunological processes at play during infection.
Ninja Nerd on Youtube (bless his soul) has made excellent videos on the physiopathology of TB and the workings of some of the anti-TB drugs.