Phenotypic heterogeneity enables uropathogenic XXXX to evade killing by antibiotics and serum complement.

@entity4258 @entity4509 @entity869 @entity293 @entity526
UNASSIGNED: Uropathogenic strains of @entity526 (UPEC) are the major cause of @entity293 . Survival in the bloodstream is associated with different mechanisms that help to resist serum complement-mediated killing. While phenotypic heterogeneity of bacteria has been shown to influence antibiotic tolerance, the possibility that it makes cells refractory to killing by the immune system has not been experimentally tested. In the current work we asked whether the heterogeneity of bacterial cultures is relevant to bacterial targeting by the serum complement system. We monitored cell divisions in the UPEC strain CFT073 with fluorescent reporter protein. Stationary phase cells were incubated in active or heat-inactivated human serum in the presence or absence of different antibiotics ( @entity869 , @entity4258 , @entity4509 ), and cell division and complement protein C3 binding were measured by flow cytometry and immunofluorescence microscopy. Heterogeneity in the doubling times of CFT073 cells in serum enabled three phenotypically different subpopulations to be distinguished, all of them being recognized by the C3 component of the complement system. The population of rapidly-growing cells resists serum complement-mediated lysis. The dominant subpopulation of cells with intermediate growth rate is susceptible to serum. The third population, which does not resume growth upon dilution from stationary phase, is simultaneously protected from serum complement and antibiotics.
