Bacteria reserve the right to admit and stay

CONICET researchers’ study sheds light on the mechanisms that lead the dissemination of enzymes that provide antibiotic resistance to different clinical relevance microorganisms.

Antibiotics, which have saved millions of lives and extended life expectancy along the twentieth century, are the only therapeutic arsenal against bacterial diseases. However, their excessive or incorrect uses in medicine and livestock have selected bacteria that have developed the capacity to resist antibiotic therapy. The World Health Organization (WHO) estimates that without measures to reverse this tendency, in 2050, there will be ten million of deaths per year generated by bacterial infection and that will become the main cause of death in the world.

The main resistance mechanism of bacteria is the production of proteins that inactivate antibiotics. These bacterial shields have two features: they are in constant evolution –what allowed them to adapt to new antibiotics– and can be easily transmitted between different bacterial species. Nevertheless, there are proteins that have widely spread and in more types of bacteria, whereas the others have remained confined to some pathogenic bacteria. NDM (New Delhi metallo-beta-lactamase) have disseminated in all type of bacteria, generating the so called “super bacteria,” which can resist the action of the latest antibiotics. Last September, there was a report about an outbreak of resistance in Italy due to NDM bacteria. It caused thirty deaths.

The team led by Alejandro Vila, CONICET researcher at the Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), have recently discovered a new mechanism by which the proteins that cause the resistance in different types of bacteria disseminate. The results were published in the journal Nature Communications.

“The dissemination capacity of these proteins has been traditionally attributed to mechanisms that favor the transmission of genes between bacteria. Our study reveals that, in turn, each bacterium ‘chooses and selects’ the proteins that uses to become resistant. Despite the power to provide resistance, some proteins are toxic for some bacteria, and they are not acquired by those microorganisms, what reduces their dissemination. In other words, bacteria reserve the right to admit and stay.” Carolina López explains. She is a CONICET postdoctoral fellow at IBR and first author of the work.

“In contrast, the NDM protein, which is the most disseminated between different bacteria, has made it because it is not toxic to any type of bacteria. That means that NDM achieves admission and stay in all types of bacterias,” Lisandro González describes. He is a CONICET researcher at the IBR and codirector of the study. Furthermore, in the paper, the scientists proved that that protein is secreted in vesicle membrane released by different bacterium. These vesicles are small spheres that travel transporting biomolecules that contribute to the communication between bacteria and favors bacterial infection. “The vesicles that transport NDM can protect bacteria sensible to antibiotic because they increase even more the dissemination of these enzymes,” González explains.

“These research works enhance the knowledge on the processes that enable the dissemination of these enzymes that provide resistance, what allows us to learn the extent of the dissemination of new variables of these enzymes and also to think about therapeutic alternatives that have as target the vesicle membranes that transport them and the systems that participate in their production in the different bacteria,” Vila concludes and adds: “this new paradigm in the field of antibiotic resistance represents advances in knowledge and new hopes in antibacterial therapy.”

By Jimena Zoni – IBR

Bibliographic reference:

López, C., Ayala, J. A., Bonomo, R. A., González, L. J., & Vila, A. J. (2019). Protein determinants of dissemination and host specificity of metallo-β-lactamases. Nature communications, 10(1), 1-11.