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Bacterial behavior in human blood reveals complement evaders with some persister-like features

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Evaders are rare, complement-resistant, phenotypic variants.

(A) Prolonged exposure of P. aeruginosa to plasma results in killing curves reminiscent of those that characterize persister formation. The three complement-sensitive strains PA14, CLJ1 and IHMA87 were incubated for 6 h in a pool of human plasma, and their survival was measured every 45 min to determine the kinetics of their survival. (B) The evader phenotype is reversible and not the result of fixed mutations. Following a first challenge, a single “evader” colony was re-cultured to assess the survival of its progeny (circle) in pooled plasma during 3 h. Survival was compared to that of a population that was never exposed to complement (square). (C) Evaders are a common feature among Gram-negative bacteria. A. baumannii, B. multivorans, enteroaggregative E. coli, K. pneumoniae, and Y. enterocolitica were incubated in pooled human plasma for 3 h, and their survival was assessed hourly. (D) The reversibility of the tolerant phenotype was assessed in individual colonies as in (B). Data represent mean ± SD of three independent experiments (A to D). Note that for K. pneumoniae in (D), the three experimental points were not pooled as one resistant mutant was isolated, presenting a survival profile different from the two other evader clones. nd: non-detected.

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doi: https://doi.org/10.1371/journal.ppat.1008893.g003