Mexico City

Scarlet Rendleman (MLA I ‘21)

Antibiotics are pharmaceutical medications designed to kill bacterial infections in humans and animals. When bacteria adapt abilities to avert antibiotics, the process of antibiotic resistance occurs. Thus, the medication becomes less effective and the resistant bacteria are harder to treat. According to the World Health Organization, “Antibiotic resistance is one of the biggest threats to global health, food security, and development today”. Although antibiotic resistance occurs naturally, the surge in misuse of antibiotic drugs in humans and animals accelerates the process and number of resistant bacteria in a system. Furthermore, the resistance of microbes develops at a faster rate than the pharmaceutical sector can adapt. This resistance leads to compromised health, longer hospital stays, higher medical expenses and increased mortality.

Mexico City contains several sources of antibiotic consumption and disposal that reveal the potential volume of antibiotics and resistant bacteria traveling through the waste stream, eventually reaching the Mezquital agricultural fields. Yet, it is first important to explain how these antibiotics reach Mexico.

As a survival mechanism, microorganisms such as bacteria and fungi have exhibited antimicrobial behavior in the environment for hundreds of millions of years, notably in soils. These bacteria are reproduced in pharmaceutical laboratories around the world. The result is a marketable antibiotic medication for global distribution. These medications are sold to local and franchise distributors such as hospitals and pharmacies. In Mexico City, pharmacies are found in abundance. In some areas, they are located on several street corners in a row. Consequently, the spatial frequency of pharmacies provides citizens with relatively easy access to antibiotics such as Penicillin, Ciprofloxacin and Streptomycin.

Yet, the spatial configuration is only one factor in accessibility. Health care, government policy and enforcement practices have been fundamental to patterns of antibiotic consumption in Mexico City. Mexico’s federal government requires a prescription for many antibiotic drugs, yet until recently, this policy has not been rigorously enforced. This has allowed pharmacists to sell antibiotics over-the-counter at low prices, encouraging unregulated self-prescription. Additionally, doctors have been known to misprescribe antibiotics for viral infections such as the cold or flu. This has no effect on the infection except for potentially making it worse, especially with drugs like Sulfamethoxazole. Over a series of decades, the lack of medical compliance has exacerbated the misuse and overuse of antibiotic medication. Thus, the sheer quantity of antibiotics moving through the Mexico-Mezquital system has exponentially increased as population and overconsumption swells. Wide-spread distribution, differential healthcare practices and the subsequent rise of the pharmaceutical empire has made this a common phenomenae afflicting the global community.

Hospitals are also important to the equation as they require a large supply of antibiotics on hand for the hundreds of admitted patients in a given week. The concentration of people taking antibiotics, as well as other medications, is potentially more dense than other locations in the city. Resistant bacteria can also proliferate in these congested spaces and spread into the greater community.

Once ingested, the antibiotic moves through and exits the body via the gastrointestinal tract. Along with antibiotics, any resistant bacteria is also excreted. Subsequently, trillions of bacteria, such as E. coli, enter the waste stream through the ubiquitous toilet every day. This becomes the primary conduit for antibiotic medication and resistant genes to reach the sewer, wastewater treatment plant and then the Mezquital Valley. The city’s impervious surfaces, dry soils, and drainage systems ensure that all water is effectively drained away and out of the city, eventually landing in the Mezquital. This condition is a stark contrast to the permeable, wet soils of the Mezquital Valley absorbing the enormous input from the city every day.

Volcanic composition of soils and groundwater extraction in the region of Mexico City has created a complex system of differential subsidence. Many areas in Mexico City have experienced moderate to severe infrastructural damage from sinkholes, further exacerbated by earthquakes. Subsidence has caused breakages of subsurface infrastructure such as pipes and sewer systems. Leakage of sewer effluent could seep through soil horizons and allow entry of resistant bacteria and chemical contaminants into nearby freshwater sources. In this case ,high concentrations of resistant bacteria could proliferate with unknown consequences.

In conclusion, the formation of soils in the Mezquital have been directly impacted by the socio-economic, political and spatial conditions of antibiotic consumption in Mexico City. Increased antibiotic use encourages the development and multiplication of resistant bacteria, which has the potential to cycle back through contact with soil and crops grown in the Mezquital. This sequence of cause and effect has enormous implications for the future of public health in Mexico and the Mezquital as an agricultural system.

Microbial life and interactions are extremely complex and difficult to control. Yet, healthcare practices, government policy and enforcement play significant roles in how much and how quickly resistant bacteria is proliferating downstream. When considering the use of wastewater at an urban scale, it is necessary to understand how bacteria move through a system. The soil is a reservoir for billions of microbial interactions. And although we may only understand a fraction of these processes, microorganisms are in constant interaction with humans and animals.

Design and environmental engineering efforts need to give greater consideration for soil as an ecosystem. It is a reservoir that supports billions of lifeforms. It is the receiver of organic and synthetic inputs from humans that change organismic and biochemical relationships on a multiplicity of scales. When dealing with a situation as complex as the Mexico-Mezquital system, there is no easy solution. It will take many sectors on both sides of the pipeline to understand and mitigate the proliferation of microbial resistance for the future of both environmental and public health.




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Heavy metals, QnrB1, Streptomyces Bacterial Colony, Penicillin Binding Proteins, Plasmid, Livestock, DNA, Penicillium Fungii




Mezquital

Samuel Gilbert

For the past century, the soils of the Mezquital Valley have received millions of tons of waste water every day. Since the advent of pharmaceutical antibiotics in the 1950s, this water has included these chemical compounds which travel from the hospitals and pharmacies of Mexico City from, through the human body, the sewer system, the wastewater treatment and canal system, finally to be distributed by an extensive network of irrigation canals that farmers use to flood and saturate their agricultural fields. Antibiotics travel in the company of the entire gut microbiome of the 22 million inhabitants of the city plus two to three million annual tourists and the chemical effluent from countless industrial plants. Together with the evolutionary history of the bacterial genome, the history of the medical and dietary conditions of the city, the aquatic and organic substrate in which the bacteria reside, these elements comprise the resistance determinants for ever-changing bacterial resistome and its capacity to disseminate and evolve. The resistome itself comprises all of the genetic adaptations that have persisted within bacterial DNA over the course of millions of years that have created antibiotic resistance in response to the antibiotic chemicals produced naturally by other organisms, environmental factors, and by human science. The soil is thus a receptacle for, as well as a battle ground in the ongoing development of the resistome.

In addition to receiving bacteria and antibiotics from Mexico City, the Mezquital valley is also home to livestock farms that raise cattle for meat and milk, pigs, and poultry. Worldwide, the livestock industry has adopted widespread use of antibiotics which are distributed as a prophylactic to the entire stock of animals. Animal husbandry accounts for 60%-80% of antibiotics produced globally. These antibiotics are used to promote rapid growth and prevent infection. They are subsequently dispersed via urine and manure into the groundwater, surface runoff channels, and to other sites in the form of fertilizer for agricultural crops. While farm workers are most directly exposed the soils, animals, and plants of the Mezquital, antibiotics can be absorbed by plants through their roots and redistributed to the people of Mexico City in the form of agricultural produce. and they remain in the tissue and products of animals which are consumed as meat or milk.


This diagram depicts the cyclical interactions between anthropogenic resistance determinants, the endemic processes of the soil, and the externalization of the resistome via agricultural products.

Soil is a profoundly important substance and medium for microbial activity and particularly for activity contributing to the resistome. The Mezquital Valley is an example of intense anthropogenic soil modification, but soils around the world have taught us much about the origins of antibiotic resistance:

“Although some evidence correlates between anthropogenic factors and elevated levels of antibiotic resistance in soil, it is becoming increasingly clear that un-impacted and pristine soils contain highly diverse and abundant levels of antibiotic resistant bacteria, which harbor a wide array of clinically-associated and novel antibiotic resistance genes. This has led to the resistome hypothesis, which speculates that many pathogen-associated antibiotic resistance genes originated in antibiotic-producing soil bacteria and reached pathogens via horizontal gene transfer.”



While bacteria do not share genetic material through sexual reproduction, they are still able to pass genes directly from one bacterium to another, a process known as horizontal gene transfer. When it comes to fostering a robust resistome, this process is in some ways much more efficient than sexual reproduction because it allows for the proliferation of targeted and specific antibacterial genes within a single species and even between different species. Over time, the resistant bacteria in a population can come to dominate as the non-resistant strains are killed off. Over long periods of sustained exposure to antibiotics in conditions like those of the wastewater digester tanks of Atotonilco and the conditions present throughout the agricultural fields of the Mezquital Valley, high concentrations of antibiotic resistant bacteria can flourish.


Horizontal gene transfer is achieved by externalizing and absorbing fragments of genetic material called plasmids as part of a process called conjugation. Plasmids contain the single or multiple genes required to establish antibiotic resistance. These genes have evolved over millions of years in order to combat the naturally occurring antibiotic chemicals produced by other species of bacteria and fungi. Studies of ancient soils preserved in permafrost have shown that the exact same resistance mechanisms that have revealed themselves in response to modern pharmaceutical antibiotics have been operating for millenia, suggesting that increased use of certain chemicals has triggered a reactivation of particular portions of the resistome. This has occurred because the sources of our clinically administered antibiotics are bacterial families such as streptomyces and fungi such as penicillium, both microorganisms that reside naturally in the soil. Overprescription and unregulated access to antibiotics in many parts of the world including Mexico City has led to a flood of broad-spectrum antibiotics such as Ciprofloxacin and Sulfamethoxazole into the environment where it can trigger resistance selection not only among the pathogenic bacteria that it is intended to target, but all of the beneficial and benign bacteria that live naturally in the soil and the human body. Due to the nature of horizontal gene transfer, the shere ubiquity of resistance genes poses problems for the development of superbugs that do not respond to any anthropogenically produced antibiotics.

Another resistance determinate compounding and complicating resistome activity is the presence of heavy metals in the soils of the Mezquital Valley. For many years, industrial waste containing lead, nickel, cadmium, mercury, and other biologically toxic heavy metals has been pumped through the clay-rich soils of the valley. The clay of the Mezquital valley is particularly “sticky” and its platelet structure retains metals for a very long time. Evidence has shown that cross-resistance to heavy metals as well as certain types of antibiotics has been detected where industrial effluent has concentrated. This means that even without the presence of antibiotics in the soils, the likelihood that bacteria would develop resistance to them is great because that resistance is shared at a genetic level to that of heavy metals.

High levels of antibiotic resistant genes have been found to exist in the rhizosphere layer of the soil, which is considered a “hot spot” of the resistome where the microbiology of the soil is the most abundant as it interacts with that of plants in ways that are still somewhat mysterious. It is clear that root-associated bacteria and fungi release antibiotics for combative purposes to protect plants from pathogens, but it is possible that some antibiotic compounds have more subtle functions in soil biology. For instance, it appears that some antibiotic chemicals produced in the rhizosphere such as tobramycin, tetracycline, and norfloxacin are not deployed as a means of killing or harming other microbes, but are expressed at “sub-toxic” levels that that can trigger secretions and behaviors that enable survival within and between species. Understanding the rhizosphere may help us to better understand the origins of the resistome and the complexity of the interactions that occur in order to maintain the plant and animal life that we depend on. It may just offer us a better understanding of how we fit into this world that is ultimately dominated by microorganisms.




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