New antibiotic resistance gene discovered hidden in the microbiome

The microbiome is still a treasure trove for science. This immense ecosystem of microbes (viruses, bacteria and fungi, among others) that populates the gut and other parts of the body helps humans with basic functions such as protecting them from external pathogens or metabolizing certain foods. But the scientific community is still trying to clearly describe everything that happens there and how exactly the inhabitants of this small, great living universe behave. A study recently published in the International Journal of Antimicrobial Agents has delved into the depths of this microbial universe and has discovered a new antibiotic resistance gene (ARG) hidden in bacteria in the microbiome. The research suggests that this microbial universe in the intestine may be a reservoir of resistant genes capable of jumping from one bacterium to another.

The discovery sheds light on a new, unknown corner of the complex human microbiome, and also provides insight into one of the greatest health threats facing the modern world: superbugs. Antibiotic-resistant microbes cause 1.7 million deaths a year worldwide and, according to a projection published in The Lancet last September, could kill more than 39 million people directly and 169 million indirectly (through association with other pathologies) over the next quarter-century.

The research identified a new gene (NpmC) capable of neutralizing the action of aminoglycosides, a family of antibiotics used to treat serious bacterial infections. The scientists found this enzyme in an inhospitable place in human and animal microbiomes in China and Canada: it was hidden in non-cultivable bacteria whose complete genomes are unknown. “We cannot cultivate 98% of the world’s bacteria; we cannot make them grow in the laboratory for various reasons [because they take months to grow, because they feed on other bacteria, because laboratory conditions are toxic to them...]. We only know them from the [partial] genomic information that we extract from feces,” explains the author of the study, Bruno González-Zorn, director of the Antimicrobial Resistance Unit at the Complutense University of Madrid and advisor to the World Health Organization (WHO) in this field.

Using these genomic data of unknown function collected in animal and human samples from China and Canada, the researchers were able to synthesize these partial gene sequences in the laboratory and study and understand their behavior. “We saw that expressing these genes in bacteria in the laboratory confers high levels of resistance to this family of antibiotics, aminoglycosides, which are widely used in intensive care units,” explains the scientist. Specifically, what this gene does, the microbiologist points out, is to place a molecule [a methyl group] in the ribosome, which is a structure of the bacterial cell that physically prevents these antibiotics from binding to the ribosome and performing their antibacterial function.

“We are just beginning to discover the dark matter of the intestine. The microbiome is a reservoir of antibiotic resistance genes waiting to be discovered,” says González-Zorn. Researchers are analyzing new families of genes capable of circumventing the effect of antibiotics and, according to the UCM microbiologist, there are already international scientific groups working “to prevent the creation of this methyl group or to resensitize these bacteria.”

More genomic surveillance

However, there are still many mysteries to be solved regarding the role played by the microbiome in antibiotic resistance, the expert admits: “Techniques do not yet allow us to know in depth the composition of the human microbiome. The entire genome of all bacteria or of bacteria that are present in very small quantities is not known.” In this sense, the microbiologist focuses on strengthening genomic surveillance to tackle one of the major global threats to health: “The discovery of NpmC as a new mechanism of resistance to aminoglycosides is a wake-up call to intensify genomic surveillance and reinforce global strategies for controlling antimicrobial resistance from a One Health perspective [a comprehensive approach to balance and optimize human, animal and environmental health].”

María del Mar Tomás, a microbiologist at the A Coruña University Hospital Complex and spokesperson for the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), highlights that the newly discovered antibiotic resistance gene “has been found in non-pathogenic bacteria and it must be taken into account that it could reach the clinical setting.” That is to say, it could jump from a non-harmful bacteria to a pathogenic one and make this microbe that causes infections resistant to this family of antibiotics.

“It is very difficult to prevent this gene from reaching a clinical setting, but this study can serve to develop new aminoglycosides or antibiotics that avoid this resistance mechanism. It is also necessary to analyze which are the mobile elements that can transmit this gene from one bacterium to another to avoid transmission. But more studies of the genomic environment of this gene are required,” reflects the microbiologist, who has not participated in this research.

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