Drug tolerance is an acute defence response preceding a fully drug-resistant state and tumour relapse; however, there are few therapeutic agents targeting drug tolerance in the clinic.
For some drugs, however, subsequent accumulation of mutations creates fully drug resistant mutants [34].
However, whilst K-1 was fully drug-susceptible, K-2 was resistant to all first line drugs (INH, RMP, ethambutol (EMB), pyrazinamide (PZA) and streptomycin (SM)).
Recombination may be important, for example, in combining resistance mutations into a single genome to achieve fully drug-resistant strains [10], [11].
We have assumed the shortest genetic distance possible between wildtype and fully drug resistant mutants (one mutation is sufficient to create full resistance against a single drug, three distinct mutations are required for full resistance against a triple-drug combination).
This implies that in vivo the inducer combination could possibly be applied for a longer time frame than the 80 days utilized in our model, if the genetic distance between wildtype and fully drug resistant mutant was greater than considered here (greater than one point mutation).
All the Beijing genotype strains were fully drug sensitive.
All cultures were fully drug sensitive with the exception of one, which was monoresistant to isoniazid.
Nine of the 11 TB patients had fully drug-sensitive organisms.
In all, 89% of all patients were fully drug compliant: 87.6% in the PSK group and 91.2% in the control group.
Although mutations that confer drug resistance can imply a fitness cost, some MDR Mtb genotypes are able to overcome this disadvantage and are as virulent as fully drug-sensitive genotypes [ 43].
