Antimicrobial resistance (AMR) contributes to almost 5 million deaths annually, worldwide (source: WHO). To mark World AMR Awareness Week (18th-24th November), we are highlighting how UniProt supports global AMR research efforts.
The language of germ warfare may be emotive, but fighting AMR is a bit like an arms race - every time we develop new antibiotics, microbes acquire ways to resist them. Only a few years after the discovery of a natural beta-lactam drug, penicillin, bacteria were isolated which were capable of inactivating this antibiotic, because they made penicillin-degrading enzymes. These enzymes are called beta-lactamases. Chemists then developed modified penicillins, including a class known as carbapenems, to deal with the problem of AMR. Carbapenems were effective for some time, as many beta-lactamases, e.g. GES-1, could not degrade this new class of drugs. However beta-lactamases acquired modifications, sometimes just a single amino acid, to confer carbapenem resistance e.g. in GES-5. And so the fight continues.
Another important class of proteins involved in AMR confers resistance not by degrading antibiotics, but instead by blocking antibiotic binding through modification of the bacterial cell wall. Examples include an enzyme called Mcr-2 which catalyzes the addition of a phosphoethanolamine moiety to lipid A in the cell wall, thereby conferring resistance to colistins, an antibiotic class which is often a treatment of last resort.
Alliances supporting the fight against AMR
UniProt has a long history of curating microbial proteins, including AMR targets; recently, we have focused on curation of AMR-associated proteins with high clinical priority. We initially concentrated on beta-lactamases belonging to clinically important subfamilies and then diversified to proteins involved in resistance to antibiotics which are often considered last-resort choices, such as vancomycin and the colistins. More recently, curation targets included proteins indirectly involved in AMR, such as those associated with biofilm formation, e.g. BrlR, because biofilms act as a permeability barrier and the bacteria inside are protected from antibiotics.
A wide range of experimental data is added to each entry including information related to the function of the protein as shown in the section from the BrlR record below.
One of the great strengths of UniProt is its role as a central data hub, linking resources and encouraging alliances. We link to general microbial biological resources such as EnsemblBacteria and EcoCyc, and have recently added links to a key resource directly related to AMR: the Comprehensive Antibiotic Resistance Database (CARD), as exemplified in the section from the MdtF record below. These links connect users to information in specialised resources, allowing easy access to other collections.
Community feedback is enormously helpful, so please help us in the ongoing battle against AMR by suggesting annotation priorities using our contact form - which AMR-related proteins should we be curating next?
