Chalmers University of Technology Professor Erik Kristiansson and co-authors have identified over 70 new metallo-?-lactamase genes that make bacteria resistant to last-resort antibiotics.
“Metallo-?-lactamases are bacterial enzymes that provide resistance to carbapenems, the most potent class of antibiotics,” Professor Kristiansson and colleagues said.
“These enzymes are commonly encoded on mobile genetic elements, which, together with their broad substrate spectrum and lack of clinically useful inhibitors, make them a particularly problematic class of antibiotic resistance determinants.”
“We hypothesized that there is a large and unexplored reservoir of unknown metallo-?-lactamases, some of which may spread to pathogens, thereby threatening public health.”
“The aim of this study was to identify new metallo-?-lactamases of class B1, the most clinically important subclass of these enzymes.”
The findings, released this month by the journal Microbiome, more than double the number of known B1 metallo-?-lactamases.
“Based on a new computational method using an optimized hidden Markov model, we analyzed over 10,000 bacterial genomes and plasmids together with more than 5 terabases of metagenomic data to identify novel metallo-?-lactamase genes,” the authors explained.
“In total, 76 novel genes were predicted, forming 59 previously undescribed metallo-?-lactamase gene families.”
“The ability to hydrolyze imipenem in an Escherichia coli host was experimentally confirmed for 18 of the 21 tested genes.”
“Our study shows that there are lots of unknown resistance genes. Knowledge about these genes makes it possible to more effectively find and hopefully tackle new forms of multi-resistant bacteria,” Professor Kristiansson said.
“The more we know about how bacteria can defend themselves against antibiotics, the better are our odds for developing effective, new drugs,” added study co-author Professor Joakim Larsson, from the University of Gothenburg.
The next step for the team is to search for genes that provide resistance to other forms of antibiotics.
“The novel genes we discovered are only the tip of the iceberg. There are still many unidentified antibiotic resistance genes that could become major global health problems in the future,” Professor Kristiansson said.
Fanny Berglund et al. 2017. Identification of 76 novel B1 metallo-?-lactamases through large-scale screening of genomic and metagenomic data. Microbiome 5 (134); doi: 10.1186/s40168-017-0353-8