We are currently on the verge of a global crisis because antibiotics are no longer effective, thus putting at risk a large part of the development achieved by modern medicine.
In fact, more than 70% of the pathogenic bacteria that cause hospital infections are resistant to multiple antibiotics, which makes the treatment of such infections highly problematic. In addition, it is estimated that by 2050, 10 million human lives will be at risk annually due to increased resistance to antibiotics if the solutions are not found on time.
Antibiotics are chemical substances that cause the death of bacteria or, failing that, inhibit their growth. These substances are produced naturally by bacteria and fungi, mainly by those who live in the soil.
In nature, antibiotics fulfill different ecological roles. The microorganisms that produce them use them as chemical weapons to compete with each other and as signaling molecules to communicate chemically and promote coordination between different individuals.
Since the mid-twentieth century, these compounds are also used in medicine and veterinary medicine as a therapeutic tool for the treatment of bacterial infections. Together with vaccines, they are one of the medical developments that has contributed the most to our survival and quality of life.
Unfortunately, in recent decades its effectiveness has decreased as a result of its misuse and abuse. Both practices have led to an increasing emergence and spread of antibiotic resistance genes (ARGs) and, concomitantly, the emergence of resistant bacteria to these antibiotics (ARBs).
It is important to emphasize that, when we supply an antibiotic for medical or veterinary use, it is only partially metabolized and, consequently, a large part of the antibiotic administered is excreted through urine and feces.
Thus, antibiotics and their degradation products end up in urban wastewater treatment plants, to be subsequently discharged into the environment through the effluent of these facilities. The application of sewage sludge and organic amendments of animal origin (such as manure and slurry) to agricultural soils also contributes to the presence of antibiotics, ARG and ARB in the environment.
A transmissible characteristic
Antibiotic resistance genes have allowed ancestral coexistence between antibiotics and bacteria, enabling them to survive in their presence. These DNA fragments can be transferred between bacteria in two well-differentiated ways:
- On the one hand, by transferring genetic material from parental bacteria to daughter bacteria, in a process called vertical gene transfer.
- On the other hand, horizontal gene transfer occurs when two unrelated bacteria transfer genetic material. One of the greatest evolutionary advantages of horizontal transfer is the rapid and efficient acquisition, by the recipient bacteria, of genes that allow them to survive in hostile environments.
- The horizontal transfer of genes between bacteria can occur, in turn, through three mechanisms.
- In the process called transformation, bacteria take DNA directly from the environment around them, thus incorporating new genes.
- Bacteriophages or phages (viruses that infect bacteria) can transport fragments of the bacterial chromosome, including ARG, when they pass from one bacterium to another during the lytic phase. This phenomenon is called transduction.
- Through conjugation, a conjugative plasmid – a circular DNA molecule containing ARG and the genes that allow its propagation – is transferred from one bacterium to another by a process that requires direct contact between the two.
In the latter case, the recipient bacterium not only acquires ARGs, but receives all the plasmid that hosts them. This allows it to transfer ARG to other bacteria, actively contributing to the spread of antibiotic resistance among bacteria.
A problem of global scale
The antibiotics released in the water and the soils exert a selective pressure on the environmental bacteria -they obligate them to acquire ARG in order to survive-, promoting the dissemination of antibiotic resistance genes and with it the proliferation of resistant bacteria. These microorganisms can, in turn, transmit ARGs through conjugative plasmids or other mobile genetic elements to other bacteria, including human pathogenic bacteria.
From the University of the Basque Country, together with two other research centers of the Basque Autonomous Community (Neiker and BC3 Basque Center for Climate Change), we have launched the Joint Research Lab initiative on Environmental Antibiotic Resistance to study, monitor and develop strategies for action against to this growing problem.
Achieving a solution requires a multidisciplinary approach, involving, among others, clinical professionals and the agricultural and livestock sector, as well as experts in evolution and the environment.
Most likely, it will be necessary to combine different therapeutic strategies such as the rationalization of the use of antibiotics, the search for new antibiotics and other molecules with antimicrobial capacity, the use of viruses as an alternative to antibiotics, the development of inhibitors of the conjugate transplant of bacterial communities that can compete with pathogens.