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

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Abstract

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.

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Fig. 1

Adapted from Abokhalil et al. [17]

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This research did not receive any specific grant from funding agencies in the public, commercial, or nonprofit sectors.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Organization of African Unity St., Abbassia, POB: 11566, Cairo, Egypt

    Rana N. Abokhalil, Walid F. Elkhatib, Mohammad M. Aboulwafa & Nadia A. Hassouna

  2. Department of Microbiology and Immunology, School of Pharmacy & Pharmaceutical Industries, Badr University in Cairo (BUC), Entertainment Area, Badr City, Cairo, Egypt

    Walid F. Elkhatib

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  1. Rana N. Abokhalil
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Contributions

RA: Design and conduction of experiments, data collection and presentation, draft writing of the manuscript. WE: Experimental design, data analysis, interpretation, supervision, revise manuscript. MA: Conception of the research idea, supervision, interpretation of data, manuscript writing and final editing. NH: Data analysis and interpretation, supervision, manuscript revision. All authors have read and approved the final manuscript.

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Correspondence to Mohammad M. Aboulwafa.

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Abokhalil, R.N., Elkhatib, W.F., Aboulwafa, M.M. et al. Persisters of Klebsiella pneumoniae and Proteus mirabilis: A Common Phenomenon and Different Behavior Profiles. Curr Microbiol 77, 1233–1244 (2020). https://doi.org/10.1007/s00284-020-01926-3

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