s. Heterogeneity analysis is, therefore, essential to our understanding of how the selective and neutral forces shape bacterial populations over a short period of time \[[@B1]-[@B4]\].

In *S. aureus*, the role of microevolution is especially significant, in which heterogeneity is hypothesized to be the basic molecular mechanism for drug resistance \[[@B5]\]. Indeed, pre-existing drug-resistant mutants were often detected, from which drug-resistant mutants emerged during drug therapy or on the drug-containing growth medium. *S. aureus*strain of PC-1, PC-2 and PC-3 are great examples \[[@B6]\]. They were isolated at different stages of vancomycin therapy. The first two were recovered from a patient in the early stages of vancomycin therapy, whereas the third was isolated one day before the patient\'s death. The minimal inhibitory concentration of vancomycin is 2 μg per milliliter for PC-1 and PC-2, while PC-3 is capable of growing on agar plates containing vancomycin at a concentration of 8 μg per milliliter at a frequency of approximately 10^-3^. PC-3\* is a colony picked from PC-3 strains capable of growing on agar containing 8 μg of vancomycin per milliliter. The new isolate can even grow on 16 μg of vancomycin per milliliter at a frequency of approximately 10^-5^, a strong indicator for the existence of subpopulations. Similarly, mutants with higher vancomycin resistance were also picked from MM66 plated on vancomycin containing agar with a minimum inhibitory concentration \[[@B7],[@B8]\].

The heterogeneity is not unique to *S. aureus*. It is found in the population of *Mycobacterium tuberculosis*and many other bacterial pathogens, where the pathogen can gain drug resistance under the selective pressure of drug therapy. Post et al identified drug-resistant subpopulations within TB patients \[[@B9]\], in which four of the 13 patients acquired additional drug-resistance mutations during the course of treatment \[[@B9]\]. On the other hand, the bacterial pathogen could also lose its pathogenicity when select