Multidrug tolerance

Multidrug tolerance or antibiotic tolerance is the ability of a disease-causing microorganism to resist being killed by antibiotics or other antimicrobials. It is mechanistically distinct from multidrug resistance: It is not caused by mutant microbes, but rather by microbial cells that exist in a transient, dormant, non-dividing state. Microorganisms that display multidrug tolerance can be bacteria, fungi or parasites.

Recognition of antibiotic tolerance dates back to 1944 when Joseph Bigger, an Irish physician working in England, was experimenting with the recently discovered penicillin. Bigger used penicillin to lyse a suspension of bacteria and then inoculated culture medium with the penicillin-treated liquid. Colonies of bacteria were able to grow after antibiotic killing. The important observation that Bigger made was that this new population could be again be killed by penicillin except for a small residual population. Hence the residual organisms were not antibiotic resistant mutants but rather a subpopulation of what he called ‘persisters’. The formation of persisters is now known to be a common phenomenon that can occur in response to a variety of antibiotics.

Multidrug tolerance is caused by a small subpopulation of microbial cells termed persisters. Persisters are not mutants, but rather are dormant cells that can survive the antimicrobial treatments that kill the majority of their genetically identical siblings. Persister cells have entered a non- or extremely slow-growing physiological state which makes them insensitive (refractory or tolerant) to the action of antimicrobial drugs. When such persisting microbial cells cannot be eliminated by the immune system, they become a reservoir from which recurrence of infection will develop. Indeed, it appears that persister cells are the main cause for relapsing and chronic infections. Chronic infections can affect people of any age, health, or immune status.

Bacterial multidrug or antibiotic tolerance poses medically important challenges. It is largely responsible for the inability to eradicate bacterial infections with antibiotic treatment. Persister cells are highly enriched in biofilms, and it has been suggested that this is the reason that makes biofilm-related diseases so hard to treat. Examples are chronic infections of implanted medical devices such as catheters and artificial joints, urinary tract infections, middle ear infections and fatal lung disease .

...
Wikipedia