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. 2022 Oct 28;23(21):13069.
doi: 10.3390/ijms232113069.

Combined Application of Aminoglycosides and Ascorbic Acid in the Elimination of Proteus mirabilis Rods Responsible for Causing Catheter-Associated Urinary Tract Infections (CAUTIs)-A Molecular Approach

Paulina Stolarek  1 , Przemysław Bernat  2 , Antoni Różalski  1
Affiliations

Combined Application of Aminoglycosides and Ascorbic Acid in the Elimination of Proteus mirabilis Rods Responsible for Causing Catheter-Associated Urinary Tract Infections (CAUTIs)-A Molecular Approach

Paulina Stolarek et al. Int J Mol Sci. .

Abstract

Proteus mirabilis is a common cause of catheter-associated urinary tract infections (CAUTIs). In this study, we verified the effectiveness of amikacin or gentamicin and ascorbic acid (AA) co-therapy in eliminating uropathogenic cells, as well as searched for the molecular basis of AA activity by applying chromatographic and fluorescent techniques. Under simulated physiological conditions, a combined activity of the antibiotic and AA supported the growth (threefold) of the P. mirabilis C12 strain, but reduced catheter colonization (≤30%) in comparison to the drug monotherapy. Slight modifications in the phospholipid and fatty acid profiles, as well as limited (≤62%) 2',7'-dichlorofluorescein fluorescence, corresponding to the hydroxyl radical level, allowed for the exclusion of the hypothesis that the anti-biofilm effect of AA was related to membrane perturbations of the C12 strain. However, the reduced (≤20%) fluorescence intensity of propidium iodide, as a result of a decrease in membrane permeability, may be evidence of P. mirabilis cell defense against AA activity. Quantitative analyses of ascorbic acid over time with a simultaneous measurement of the pH values proved that AA can be an effective urine acidifier, provided that it is devoid of the presence of urease-positive cells. Therefore, it could be useful in a prevention of recurrent CAUTIs, rather than in their treatment.

Keywords: Proteus mirabilis; adhesion; aminoglycosides; ascorbic acid; catheter; fatty acids; hydroxyl radical; membrane permeability; phospholipids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The bacterial growth (column graphs) and cell adhesion to the catheter (line graphs) of the P. mirabilis ATCC 29906 (A) and C12 (B) strains after 6 and 24 h of cultivation. Legend: C—control, AA—ascorbic acid, AK—amikacin, CN—gentamicin.
Figure 2
Figure 2
Percentage content of phosphatidylethanolamines (A) and phosphatidylglycerols (B) identified in the planktonic (1) and adherent (2) cells of the P. mirabilis ATCC 29906 strain treated with ascorbic acid, amikacin, or gentamicin. Legend: C—control, AA—ascorbic acid, AK—amikacin, CN—gentamicin.
Figure 3
Figure 3
Percentage content of phosphatidylethanolamines (A) and phosphatidylglycerols (B) identified in the planktonic (1) and adherent (2) cells of the P. mirabilis C12 strain treated with ascorbic acid, amikacin, or gentamicin. Legend: C—control, AA—ascorbic acid, AK—amikacin, CN—gentamicin.
Figure 4
Figure 4
Percentage contents of FAs identified in the planktonic (A) and adherent (B) cells of the ATCC 29906 (1) and C12 (2) strains treated with ascorbic acid and/or aminoglycosides. Legend: C—control, AA—ascorbic acid, AK—amikacin, CN—gentamicin.
Figure 5
Figure 5
Changes of 2’,7’-dichlorofluorescein (DCF) fluorescence intensity in the planktonic and adherent cells of the ATCC 29906 (A) and C12 (B) strains treated with AA, AK, or CN. Legend: C—control, AA—ascorbic acid, AK—amikacin, CN—gentamicin.
Figure 6
Figure 6
Changes of propidium iodide (PI) fluorescence intensity in the planktonic and adherent cells of the ATCC 29906 (A) and C12 (B) strains treated with AA, AK, or CN. Legend: C—control, AA—ascorbic acid, AK—amikacin, CN—gentamicin.
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Grants and funding

This research received no external funding. It was supported by the Department of Biology of Bacteria (University of Lodz, Lodz, Poland).