Wednesday, July 13, 2011

An example for in vivo persisters?

Except for a few, most of the experiments demonstrating phenotypic shift of persisters are in vitro experiments only. However, a recent article reported the isolation of in vivo persisters of Candida albicans and C. glabrata from cancer patients (LaFleur et al. 2010). Those patients were on long-term treatment with topical chlorhexidine as they were at high risk of oral candidiasis. The number of persisters isolated from patients treated daily with topical chlorhexidine was determined by growing biofilms in vitro followed by  challenging the biofilms with high concentrations of amphotericin B, and plating for survivors. Persister levels were found to be higher in patients with long-term carriage than in patients with transient carriage. Fifteen hip isolates that were isolated from different patients were considered as mutants, indicating that hip mutants are involved in recalcitrant fungal infections.

However, some of the conclusions made by authors are questionable
1. authors identified isolates that showed increased survival in the presence of amphotericin B and suggested that the high persister phenotype was caused by an underlying genetic change. It is unclear how the authors concluded that the survivors had an underlying genetic change without doing any relevant studies.
2. If they had an underlying genetic change, can they be considered as persisters? (persisters are non-mutants which exhibit a transient phenotypic tolerance)
3. Moreover, the strains isolated from those patients did not show any signs of infections, as admitted by the authors. Hence, it is not known whether the presence of these persisters can cause chronic infections.

Lafleur et al. (2010). Patients with long-term oral carriage harbor high-persister mutants of Candida albicans. Antimicrob Agents Chemother 54(1), 39-44.



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