The discovery of antibiotics was one of the greatest advances in medicine, since it has allowed the effective treatment of infections caused by pathogenic bacteria. However, these compounds have been losing their effectiveness due to the diffusion of genes that confer resistance to antibiotics between bacterial cells. Bacteria have several mechanisms to cope with exposure to antibiotics, which they frequently acquire through the lateral transfer of resistance genes through mobile genetic elements, such as plasmids.
Along these lines, the team led by Miquel Sánchez-Osuna, from the Autonomous University of Barcelona (UAB), has analyzed tens of thousands of bacterial plasmid sequences with the aim of quantifying and discerning the processes that lead to the dissemination of these genes of resistance, which represent a great concern for public health.
Using genome comparison strategies, the authors of the new study have been able to establish that the degree of dispersion of different resistance genes depends mainly on their mechanism of action. The most frequently disseminated resistance genes encode highly specialized enzymes capable of selectively inactivating antibacterial compounds or selectively protecting antibiotic targets without affecting the proper functioning of the bacterial cell. On the other hand, more generic mechanisms, such as efflux pumps, which are responsible for expelling all kinds of harmful compounds, are rarely disseminated.
Additionally, the study shows that diffusion profiles of resistance vary greatly among different antibiotics, often highlighting the genes that confer resistance to the first antibiotics used in hospitals. The study reveals that the genes that confer resistance to commonly used antibiotics, such as penicillin and its various derivatives or tetracyclines, show a high degree of dissemination. On the other hand, various classes of antibiotics show very low dissemination profiles. In most of these latter cases, these are genes that confer resistance to antibiotics of specific and limited use for certain bacterial species, normally restricted to the clinical setting.
Bacterial culture plate used to test for resistance to antibiotics. Halos around the disk indicate susceptibility to the antibiotic contained in the disk, while growth around a disk means that the bacteria are resistant. (Image: Paula Bierge)
The ability to assess and control the spread of antibiotic resistance genes is essential to improve antibiotic use policy and develop predictive models of spread of new resistance. In this sense, the method proposed in this work provides the means to efficiently take advantage of the plasmid sequences available in public databases and quantitatively assess the spread of resistance genes.
The study is titled “Systematic in Silico Assessment of Antimicrobial Resistance Dissemination across the Global Plasmidome”. And it has been published in the academic journal Antibiotics. (Source: UAB. CC BY-NC 4.0)