Rosa Rubicondior: Malevolent Designer News - How Tuberculosis Is Protected During Airborne Transmission

Friday, 14 March 2025

Malevolent Designer News

How Tuberculosis Is Protected During Airborne Transmission

Scientists have discovered a family of genes that becomes essential for survival specifically when the tuberculosis pathogen is exposed to the air, likely protecting the bacterium during its flight.

Image: iStock; MIT News.

Study: Tuberculosis relies on protective genes during airborne transmission | MIT News | Massachusetts Institute of Technology

Imagine you're the designer of a nasty little pathogen that is designed to make people sick and die, but you have a problem. The organism needs to get from one victim to the next in order to spread and make as many people sick as possible, but, as an obligate pathogen, it is designed to life in the moist warm interior of its victims, so is not very good at living outside, where it needs to be, if only briefly, to get into its next victim.

Quite a problem, eh?

But not something beyond creationism's divine malevolence, it seems, because, if you accept creationists' argument for the moment, the parasitic organism that causes tuberculosis is specially designed to survive while in transit, so to speak.

Exactly how it does it has recently been discovered by researchers at the Massachusetts Institute of Technology (MIT) and their collaborators. The key to its survival is a family of genes that were previously believed to be non-essential because they had no effect when injected into a potential host but have now been shown to be essential for survival outside a host's body.

What can you tell me about the pathogenic parasite, Mycobacterium tuberculosis, especially its evolution and modes of transmission?

Mycobacterium tuberculosis: Evolution and Transmission

Overview
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), one of the deadliest infectious diseases in human history. It primarily affects the lungs but can spread to other organs. Mtb is an obligate pathogen, meaning it relies on a host for survival and transmission.

Evolution of Mycobacterium tuberculosis

Mtb belongs to the Mycobacterium tuberculosis complex (MTBC), a group of closely related bacterial species that also includes M. bovis (which causes TB in cattle), M. africanum, and M. canettii,

Origins and Evolutionary History

Ancestral Mycobacteria: The genus Mycobacterium diverged from other actinobacteria around 150 million years ago. Environmental mycobacteria, which are free-living and found in soil and water, are thought to be the ancestors of Mtb.
Obligate Pathogenicity: Mtb evolved from environmental species that were able to survive inside protozoa and macrophages. Over time, a subset adapted exclusively to mammalian hosts, losing genes necessary for free-living existence.
Human Adaptation: Mtb likely co-evolved with humans for tens of thousands of years. Phylogenetic studies suggest that human-associated strains originated in Africa and spread with human migrations.
Key Evolutionary Features

Genomic Stability: Unlike many bacteria, Mtb has a relatively stable genome with low horizontal gene transfer, possibly due to a lack of genetic recombination mechanisms.
Virulence Factors: Mtb's pathogenicity is largely due to its complex lipid-rich cell wall, which provides resistance to antibiotics, immune responses, and desiccation.
Latency and Reactivation: The ability to persist in a dormant state (latent tuberculosis infection, LTBI) is a key evolutionary adaptation that enhances its long-term survival and transmission.

Modes of Transmission

Mtb is primarily transmitted via airborne droplets, making it highly infectious. Transmission occurs in several key ways:

Airborne Transmission

Infected individuals release aerosolized droplets containing Mtb when they cough, sneeze, talk, or even breathe heavily.
These droplets can remain suspended in the air for hours in enclosed spaces.
Inhalation of just a few bacilli can lead to infection.

Direct Person-to-Person Spread

Close contact in crowded conditions (e.g., prisons, refugee camps, urban slums) increases the risk.
Immunocompromised individuals (e.g., HIV-positive patients) are more susceptible to infection and progression to active TB.

Zoonotic Transmission

M. bovis, a closely related species, can be transmitted via unpasteurized milk or direct contact with infected animals.
Historically, bovine TB was a major human health issue, but pasteurization has reduced its impact.

Environmental Transmission (Possible but Rare)

Mtb can persist in the environment for limited periods due to its robust cell wall.
Some studies suggest it may be viable in dust or fomites, but direct environmental transmission is not a primary mode.

Evolutionary Pressures and Adaptation to Humans

Mtb's success as a pathogen is due to several evolutionary strategies:

Latency and Immune Evasion: The ability to persist in a dormant state for decades enhances its survival in human populations.
Host Adaptation: Different Mtb lineages show genetic variations that correlate with human genetic diversity, suggesting co-evolution.
Antibiotic Resistance: Evolution of drug-resistant strains (MDR-TB and XDR-TB) is a modern adaptation due to selective pressure from antibiotic treatment.

Conclusion

M. tuberculosis is a highly adapted human pathogen that has co-evolved with us for millennia. Its primary mode of transmission is airborne, making it particularly challenging to control. Its evolutionary adaptations, such as latency and immune system evasion, make it one of the most persistent and dangerous infectious agents in human history. Understanding its transmission and evolution is crucial for developing better treatments and prevention strategies.

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Information Continually updated

The researchers’ findings are the subject of an open access paper in Proceeding of the National Academy of Science (PNAS). They are also explained in an article in MIT News:

Study: Tuberculosis relies on protective genes during airborne transmission
The findings provide new drug targets for stopping the infection’s spread.
Tuberculosis lives and thrives in the lungs. When the bacteria that cause the disease are coughed into the air, they are thrust into a comparatively hostile environment, with drastic changes to their surrounding pH and chemistry. How these bacteria survive their airborne journey is key to their persistence, but very little is known about how they protect themselves as they waft from one host to the next.

Now MIT researchers and their collaborators have discovered a family of genes that becomes essential for survival specifically when the pathogen is exposed to the air, likely protecting the bacterium during its flight.

Many of these genes were previously considered to be nonessential, as they didn’t seem to have any effect on the bacteria’s role in causing disease when injected into a host. The new work suggests that these genes are indeed essential, though for transmission rather than proliferation.

There is a blind spot that we have toward airborne transmission, in terms of how a pathogen can survive these sudden changes as it circulates in the air. Now we have a sense, through these genes, of what tools tuberculosis uses to protect itself.

Lydia Bourouiba, co-corresponding author
The Fluid Dynamics of Disease Transmission Laboratory
Fluids and Health Network
Department of Mechanical Engineering
Massachusetts Institute of Technology, Cambridge, MA, USA.

The team’s results, appearing this week in the Proceedings of the National Academy of Sciences, could provide new targets for tuberculosis therapies that simultaneously treat infection and prevent transmission.

If a drug were to target the product of these same genes, it could effectively treat an individual, and even before that person is cured, it could keep the infection from spreading to others.

Professor Carl Nathan, co-corresponding author
Department of Microbiology and Immunology
Weill Cornell Medicine, New York, NY, USA.

Nathan and Bourouiba are co-senior authors of the study, which includes MIT co-authors and mentees of Bourouiba in the Fluids and Health Network: co-lead author postdoc Xiaoyi Hu, postdoc Eric Shen, and student mentees Robin Jahn and Luc Geurts. The study also includes collaborators from Weill Cornell Medicine, the University of California at San Diego, Rockefeller University, Hackensack Meridian Health, and the University of Washington.

Pathogen’s perspective

Tuberculosis is a respiratory disease caused by Mycobacterium tuberculosis, a bacterium that most commonly affects the lungs and is transmitted through droplets that an infected individual expels into the air, often through coughing or sneezing. Tuberculosis is the single leading cause of death from infection, except during the major global pandemics caused by viruses.

In the last 100 years, we have had the 1918 influenza, the 1981 HIV AIDS epidemic, and the 2019 SARS Cov2 pandemic. Each of those viruses has killed an enormous number of people. And as they have settled down, we are left with a ‘permanent pandemic’ of tuberculosis.

Professor Carl Nathan.

Much of the research on tuberculosis centers on its pathophysiology — the mechanisms by which the bacteria take over and infect a host — as well as ways to diagnose and treat the disease. For their new study, Nathan and Bourouiba focused on transmission of tuberculosis, from the perspective of the bacterium itself, to investigate what defenses it might rely on to help it survive its airborne transmission.

This is one of the first attempts to look at tuberculosis from the airborne perspective, in terms of what is happening to the organism, at the level of being protected from these sudden changes and very harsh biophysical conditions.

Lydia Bourouiba.

Critical defense

At MIT, Bourouiba studies the physics of fluids and the ways in which droplet dynamics can spread particles and pathogens. She teamed up with Nathan, who studies tuberculosis, and the genes that the bacteria rely on throughout their life cycle.

MIT researchers simulated the exhalation turbulent cloud after a human cough, with microdroplets within the cloud that can travel three meters from their source.
Credit: Courtesy of the researchers

To get a handle on how tuberculosis can survive in the air, the team aimed to mimic the conditions that the bacterium experiences during transmission. The researchers first looked to develop a fluid that is similar in viscosity and droplet sizes to what a patient would cough or sneeze out into the air. Bourouiba notes that much of the experimental work that has been done on tuberculosis in the past has been based on a liquid solution that scientists use to grow the bacteria. But the team found that this liquid has a chemical composition that is very different from the fluid that tuberculosis patients actually cough and sneeze into the air.

Additionally, Bourouiba notes that fluid commonly sampled from tuberculosis patients is based on sputum that a patient spits out, for instance for a diagnostic test.

The fluid is thick and gooey and it’s what most of the tuberculosis world considers to represent what is happening in the body. But it’s extraordinarily inefficient in spreading to others because it’s too sticky to break into inhalable droplets.

Lydia Bourouiba.

Through Bourouiba’s work with fluid and droplet physics, the team determined the more realistic viscosity and likely size distribution of tuberculosis-carrying microdroplets that would be transmitted through the air. The team also characterized the droplet compositions, based on analyses of patient samples of infected lung tissues. They then created a more realistic fluid, with a composition, viscosity, surface tension and droplet size that is similar to what would be released into the air from exhalations.

Then, the researchers deposited different fluid mixtures onto plates in tiny individual droplets and measured in detail how they evaporate and what internal structure they leave behind. They observed that the new fluid tended to shield the bacteria at the center of the droplet as the droplet evaporated, compared to conventional fluids where bacteria tended to be more exposed to the air. The more realistic fluid was also capable of retaining more water.

Additionally, the team infused each droplet with bacteria containing genes with various knockdowns, to see whether the absence of certain genes would affect the bacteria’s survival as the droplets evaporated.

In this way, the team assessed the activity of over 4,000 tuberculosis genes and discovered a family of several hundred genes that seemed to become important specifically as the bacteria adapted to airborne conditions. Many of these genes are involved in repairing damage to oxidized proteins, such as proteins that have been exposed to air. Other activated genes have to do with destroying damaged proteins that are beyond repair.

What we turned up was a candidate list that’s very long. There are hundreds of genes, some more prominently implicated than others, that may be critically involved in helping tuberculosis survive its transmission phase.

Professor Carl Nathan.

The team acknowledges the experiments are not a complete analog of the bacteria’s biophysical transmission. In reality, tuberculosis is carried in droplets that fly through the air, evaporating as they go. In order to carry out their genetic analyses, the team had to work with droplets sitting on a plate. Under these constraints, they mimicked the droplet transmission as best they could, by setting the plates in an extremely dry chamber to accelerate the droplets’ evaporation, analogous to what they would experience in flight.

Going forward, the researchers have started experimenting with platforms that allow them to study the droplets in flight, in a range of conditions. They plan to focus on the new family of genes in even more realistic experiments, to confirm whether the genes do indeed shield Mycobacterium tuberculosis as it is transmitted through the air, potentially opening the way to weakening its airborne defenses.

The idea of waiting to find someone with tuberculosis, then treating and curing them, is a totally inefficient way to stop the pandemic. Most people who exhale tuberculosis do not yet have a diagnosis. So we have to interrupt its transmission. And how do you do that, if you don’t know anything about the process itself? We have some ideas now.

Professor Carl Nathan.

Significance
Mycobacterium tuberculosis (Mtb) travels from the lungs of one person through the air to the lungs of another and survives multiple stresses en route, including changes in temperature and in concentrations of oxygen, carbon dioxide, hydrogen ions, salts, and organic solutes. Here, we present a genetically tractable model of transmission to begin the identification of the transmission survival genome of Mtb. We devised a fluid that mimics TB lesions, found that it protects Mtb from transmission-related stresses, associated this with the structure of the droplets as they dry and their ability to retain water, and used it to query the potential contribution of each of Mtb’s genes to Mtb’s survival in models of three sequential stages of transmission.

Abstract
Mycobacterium tuberculosis (Mtb), a leading cause of death from infection, completes its life cycle entirely in humans except for transmission through the air. To begin to understand how Mtb survives aerosolization, we mimicked liquid and atmospheric conditions experienced by Mtb before and after exhalation using a model aerosol fluid (MAF) based on the water-soluble, lipidic, and cellular constituents of necrotic tuberculosis lesions. MAF induced drug tolerance in Mtb, remodeled its transcriptome, and protected Mtb from dying in microdroplets desiccating in air. Yet survival was not passive: Mtb appeared to rely on hundreds of genes to survive conditions associated with transmission. Essential genes subserving proteostasis offered most protection. A large number of conventionally nonessential genes appeared to contribute as well, including genes encoding proteins that resemble antidesiccants. The candidate transmission survival genome of Mtb may offer opportunities to reduce transmission of tuberculosis.

Mycobacterium tuberculosis (Mtb) is the cause of a multicentury bacterial pandemic that only occasionally yields to viral pandemics as the leading cause of human death from infection. While many pathogens of humans complete their life cycle in a reservoir other than the incidental human host, humans are Mtb’s reservoir as well as its victims. In people who are not immunosuppressed, the case fatality rate for tuberculosis (TB) is about 70% for those who have microscopically detectable Mtb in their sputum and receive no treatment (1). For a pathogen that so readily kills its reservoir, transmission is an evolutionary bottleneck (2). However, whether any Mtb genes facilitate transmission is unknown. The transmission biology of Mtb (3) has been studied epidemiologically within populations (e.g., refs. 4–7), mechanistically by exposing experimental animals to patients’ exhalations (e.g., ref. 8) and inferentially in studies that capture bacilli exhaled by people with TB (9–13). However, to our knowledge, there has been no preclinical model for studying the transmission biology of Mtb under physiologically relevant conditions at a genome-wide level. The efficacy of TB treatment is monitored by tests on sputum. However, the typical viscosity of sputum (400 to 700 mPa•s) (14) limits its potential for fragmentation into large numbers of infectious aerosols that are small enough, typically postulated to be < ~5 μm in longest dimension (15–22), to stay suspended in laminar intrabronchial airflow, escape entrapment on the bronchial ciliary escalator and pass through the narrowest bronchioles to the pulmonary alveoli of a new host. Fluids of lower viscosity are likely to generate more respirable aerosols (20, 23). While diverse fragmentation processes may generate bacteria-laden respiratory particles (22, 24), the presence of necrotic pulmonary cavities correlates with infectivity (25). Cavity contents called “caseum” for their cheese-like viscosity routinely spill into bronchi (26), where they may be diluted by low-viscosity bronchial secretions. The rheologic properties of the resulting mixture may favor respirable microdroplet formation upon the shearing and bursting fluid fragmentation expected to occur during human tidal breathing, speech, song, and violent exhalations, such as coughs and sneezes (24).

Most preclinical studies of mycobacterial biology have involved laboratory media with markedly different compositions, buffers, and osmolarities than human body fluids, often under an atmosphere—room air—that is hyperoxic (O2 ~ 21%) compared to most human tissues (O2 ~ 5%) (27) and lacks carbon dioxide. CO2 is the equilibrant that maintains the physiologic pH of the human bicarbonate buffer system, a key carbon source for Mtb’s metabolism (28) and a sensitizer to oxidant injury (29). Moreover, transmission involves not one set of environmental conditions but sequential passage through a series of environments, in each of which survival of the bacilli may require shared or distinct mechanisms of adaptation.

Here, we present the introductory study in a series of efforts of increasing technical difficulty to identify the transmission survival genome of Mtb. Constrained by the equipment available for working at genome scale under biologic safety level 3 conditions, the present paper deals with 2-μL sessile droplets of Mtb. Given that the lessons learned may apply only in part to smaller droplets that are airborne, a forthcoming study based on newly designed devices will involve microdroplets suspended in air. A third study based on other new devices will test individual Mtb genes for their role in infecting mice via aerosol particles of defined size and number.

The present study models three stages of TB transmission in vitro (Fig. 1A): 1) residence of Mtb in a hypoxic, necrotic cavity closed off from the airways; 2) erosion of such a lesion into the airways, allowing for a higher level of oxygenation and mixture with bronchial secretions; and 3) expulsion into air in rapidly desiccating microdroplets. Incubation in the model aerosol fluid (MAF) described below mimicked residence in caseum in inducing phenotypic tolerance to several TB drugs (30). Two findings emerged. First, incubation in MAF substantially preserved Mtb’s viability under conditions that model interhost transit in hyperoxic droplets whose evaporation cools and alkalinizes them as their solutes concentrate or precipitate. Second, Mtb appears to survive under these conditions by calling on large numbers of essential genes and on many genes deemed “nonessential” because their knockout, knockdown, or disruption by transposon insertion had not impaired Mtb’s survival in studies under conventional conditions in vitro or in mice.

Fluids and atmospheres modeling three stages of transmission. (A) Schematic. Part of the cartoon is adapted from Manna and Bourouiba in ref. 31. (B) Components of MAF. Organic metabolites present both in caseum and in Minimum Essential Medium-α (MEM- α) are in red. Those found in caseum but lacking in MEM-α are in green. Inorganic salts present in MEM-α are highlighted in purple, along with the organic compound bicarbonate, given its substantial contribution to the osmolality of MEM-α. Lipids are colored by class. Concentrations of each component are given in SI Appendix, Table S2 A–F. (C) Osmolality of MAF, 7H9 supplemented with glycerol and the latter further supplemented with tyloxapol, oleic acid, albumin, dextrose, and catalase at the standard concentrations listed in SI Appendix, Table S2 A–F. Means ± SEM for three measurements. The dotted line indicates the osmolality of MEM-α, which mimics human extracellular fluid. The solid line indicates values reported for mouse spleen and shaded area highlights values reported for BCG-infected mouse tissue (see text). (D) Dynamic viscosity $η$ and surface tension $γ_{G L}$ of MAF, MEM-α and its six major salts, and contact angle $θ_{0}$ of those fluids on a tissue culture-treated polystyrene surface were measured and compared to MilliQ deionized water. Density is reported in SI Appendix, Fig. S1D. Means ± SD for at least three measurements; individual values not shown where n > 10. (E) Cough cloud generated by the exhalation mimic system ExhaleSimulator (32) with a trajectory here shown to span 3 m from the source. (F) Total droplet counts within size range 0.5 to 20 µm, measured at 1 m from the source in (E). (G) Cumulative droplet size distribution of MAF particles counted in (F). Dashed lines indicate that ~94% were ≤3 µm in diameter.

To forestall the traditional creationists excuse that 'Sin' has caused 'genetic entropy', so pathogens are the result of 'devolution' (© Michael J. Behe), these genes help the bacteria survive and prosper in an otherwise hostile environment - a classic example of evolution. It is sheer biological nonsense to try to present these genes as examples of 'devolution.

Creationists second problem is the William A Dembski has asserted that complex specified genetic information is proof of an intelligent designer, and these genes are nothing less than 'complex specified information' within Dembski's definition - they are complex and specify an output in terms of enhanced survivability.

Of course, a much better explanation exists in the form of evolution by natural selection, but the creation cult would rather its dupes believed a magic invisible intelligent entity was responsible, even though that entity would have to be regarded as malevolent, if that were remotely true.

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