The Rise of Superbugs
What is Antibiotic Resistance?
Antimicrobial resistance is the ability acquired by microbes to withstand the attack by antimicrobial products. Standard treatments become ineffective when bacteria turn resistant to first-line antibiotics.
Resistance to antibiotics is a natural phenomenon originating in the exposure of bacteria to antibiotic. Like all living beings, bacteria adapt themselves to their environment (Darwin rules). When antibiotics are introduced in a medium, it exerts a selective pressure on the bacteria of the medium. The bacteria will try to evolve and adapt their genes to survive: mutations will occur and the mutations conferring resistance will be selected. Bacteria harboring the resistance-conferring genes will multiply and become predominant: we say that antibiotic-resistant bacteria have been selected.
The Molecular Mechanisms of Bacterial Resistance
The intended mechanism of action of antibiotics may be counter-acted by bacterial organisms via several different strategies. The following figure illustrates three of them commonly found in bacteria resistant to several classes of antibiotics:
- Inactivating the antibiotic via modification or degradation. It can be achieved through an antibiotic-degrading enzyme.
- Eliminating antimicrobial agents from the cell through efflux pumps. To be effective, antibiotics must be present at a sufficiently high concentration within the cell. Some bacteria possess membrane proteins that are efflux pump, extruding the antibiotic out of the cell.
- Mutating the antibiotic target. The antibiotic is active when it can bind to the target. If the target is mutated and presents a different spatial conformation, then the antibiotic cannot bind and no antibiotic activity is observed.
From Non Harmful Bacteria to Resistant Infections
The genes that confer the mechanisms of resistance to antibiotics can be transferred between bacteria: several mechanisms of genes transfer are known today such as conjugation, transformation or transduction. Consequently, multiple resistance genes can be transferred from a non harmful bacteria (such as a commensal bacteria) to another strain, for example a pathogenic one. Multi-resistant pathogens appear: they spread and cause opportunist infections that are very difficult to treat since the opportunist pathogen is resistant to multiple antibiotic classes.
Therefore, the indirect consequences of resistance are severe. Infections caused by resistant microbes fail to respond to treatment, resulting in prolonged illness and a greater odds ratio of death. Treatment failures also lead to longer periods of infection, which increase the dissemination of resistant bacteria, thus increasing the probability of inter-individual transmission and exposing the general population to the risk of contracting an infection caused by a resistant strain.
Learn more on the transfers of resistance genes in the commensal flora of the colon in the next pages!