Persisters of Klebsiella pneumoniae and Proteus mirabilis: A Common Phenomenon and Different Behavior Profiles

摘要

Persisters of infectious agents are capable of surviving antibiotic treatment so the emergence of these subpopulations need to be overcome. In this study, we aimed to isolate, characterize and inhibit persister subpopulation in two clinical isolates Klebsiella pneumoniae and Proteus mirabilis. Different behavior profiles between the two isolates could be observed. The results of dose-dependent killing curve revealed that 2.3% (Klebsiella pneumoniae) versus 1.3% (Proteus mirabilis) persister cells could be recovered using 500 and 30 ug/ml ciprofloxacin, respectively. Upon resuscitation, persister cells exhibited only 65% versus 30% percentage growth and 5 versus 7 times cell elongation relative to Klebsiella pneumoniae and Proteus mirabilis, respectively. The levels of persister cells to ciprofloxacin of Klebsiella pneumoniae were dramatically decreased by about 79, 92, 97 and 83% in average by pre-exposure to hyperosmotic stress, temperature, different pHs, and hydrogen peroxide, respectively, while those of Proteus mirabilis were minimally decreased with corresponding reduction percentages of about 12%, 24 & 25%, and 0%. Regarding combating persisters, Klebsiella pneumoniae showed different response as compared to Proteus mirabilis. Among the tested sugars, the highest reduction of Klebsiella pneumoniae persister cells was obtained with pre-priming with sucrose while for Proteus mirabilis persister cells, the highest reduction was obtained with pre-priming with glucose. Using sodium salicylate with ciprofloxacin could eradicate persisters of Klebsiella pneumoniae at any tested concentration while for Proteus mirabilis it caused some reduction in persister cells at certain concentrations. Complete eradication of persisters was obtained by combining silver nitrate with ciprofloxacin for each test isolate.