Effect of biogenic polyamines on rifampicin accumulation in Escherichia coli cells

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

The biogenic polyamines are well known to regulate cell wall permeability for antibiotics permeating the cell via porins. The effect of polyamines on the antibiotics transported by the non-porin route, such as rifampicin, has not been studied. In this work, the effect of intracellular putrescine, spermidine, and cadaverine on the efficiency of rifampicin accumulation, the bacterial susceptibility to rifampicin, the hydrophobicity of the cell surface, as well as the effect of polyamines on the expression of the marRAB operon was tested. None of the three polyamines studied affected the rate of rifampicin transport into the cell at the early stages (2 min). Under the longer exposure (60 min) a protective effect of cadaverine was observed, since the accumulation of rifampicin in cadaverine-free cells was higher compared to cadaverine-proficient ones. The absence of cadaverine in Escherichia coli cells increased their hydrophobicity. There was a direct relationship between the degree of hydrophobicity of the cell surface and the efficiency of rifampicin accumulation. Polyamines themselves did not affect the expression of marRAB operon, but modulated its expression induced by salicylate. Putrescine had no effect, spermidine decreased and cadaverine increased the expression level. Overall, polyamine biosynthesis plays a role in bacterial adaptation to rifampicin, as the strains unable to synthesize cadaverine or putrescine and spermidine were more sensitive than the wild-type strains. Cadaverine plays a special role in protecting against the effects of rifampicin; its intracellular concentration affected bacterial susceptibility to rifampicin.

Толық мәтін

Рұқсат жабық

Авторлар туралы

A. Akhova

PFRC UB RAS

Хат алмасуға жауапты Автор.
Email: akhovan@mail.ru

Institute of Ecology and Genetics of Microorganisms UB RAS

Ресей, Perm, 614081

L. Nesterova

PFRC UB RAS

Email: akhovan@mail.ru

Institute of Ecology and Genetics of Microorganisms UB RAS

Ресей, Perm, 614081

A. Tkachenko

PFRC UB RAS

Email: akhovan@mail.ru

Institute of Ecology and Genetics of Microorganisms UB RAS

Ресей, Perm, 614081

Әдебиет тізімі

  1. Методические указания по определению чувствительности микроорганизмов к антибактериальным препаратам: Методические указания. – М.: Федеральный центр госсанэпиднадзора Минздрава России, 2004. (Performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement. CLSI document M100-S24. Wayne, PA: Clinical and Laboratory Standards Institute, 2014.)
  2. Akhova A., Nesterova L., Shumkov M., Tkachenko A. Cadaverine biosynthesis contributes to decreased Escherichia coli susceptibility to antibiotics // Res. Microbiol. 2021. V. 172. Art. 103881. https://doi.org/10.1016/j.resmic.2021.103881
  3. Akhova A., Tkachenko A. Multifaceted role of polyamines in bacterial adaptation to antibiotic-mediated oxidative stress // Korean J. Microbiol. 2020. V. 56. P. 103–110. https://doi.org/10.7845/kjm.2020.0013
  4. Alekshun M. N., Levy S. B., Mealy T. R., Seaton B. A., Head J. F. The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 Å resolution // Nat. Struct. Biol. 2001. V. 8. P. 710–714. https://doi.org/10.1038/90429
  5. delaVega A.L., Delcour A. H. Cadaverine induces closing of E. coli porins // EMBO J. 1995. V. 14. № 23. P. 6058–6065. https://doi.org/10.1002/j.1460-2075.1995.tb00294.x
  6. Delcour A. H. Outer membrane permeability and antibiotic resistanc // Biochim. Biophys. Acta. 2009. V. 1794. P. 808–816. https://doi.org/10.1016/j.bbapap.2008.11.005
  7. Grossowicz N., Ariel M. Mechanism of protection of cells by spermine against lysozyme-induced lysis // J. Bacteriol. 1963. V. 85. P. 293–300. https://doi.org/10.1128/jb.85.2.293-300.1963
  8. Hancock R. E., Farmer S. W., Li Z. S., Poole K. Interaction of aminoglycosides with the outer membranes and purified lipopolysaccharide and OmpF porin of Escherichia coli // Antimicrob. Agents Chemother. 1991. V. 35. P. 1309–1314. https://doi.org/10.1128/AAC.35.7.1309
  9. Harmon D. E., Ruiz C. The multidrug efflux regulator AcrR of Escherichia coli responds to exogenous and endogenous ligands to regulate efflux and detoxification // mSphere. 2022. V. 7. Art. e0047422. https://doi.org/10.1128/msphere.00474-22
  10. Kojima S., Kaneko J., Abe N., Takatsuka Y., Kamio Y. Cadaverine covalently linked to the peptidoglycan serves as the correct constituent for the anchoring mechanism between the outer membrane and peptidoglycan in Selenomonas ruminantium // J. Bacteriol. 2011. V. 193. P. 2347–2350. https://doi.org/10.1128/JB.00106-11
  11. Leus I. V., Adamiak J., Chandar B., Bonifay V., Zhao S., Walker S. S., Squadroni B., Balibar C. J., Kinarivala N., Standke L. C., Voss H. U., Tan D. S., Rybenkov V. V., Zgurskaya H. I. Functional diversity of Gram-negative permeability barriers reflected in antibacterial activities and intracellular accumulation of antibiotics // Antimicrob. Agents Chemother. 2023. V. 67. Art. e0137722. https://doi.org/10.1128/aac.01377-22
  12. Li X. Z., Plésiat P., Nikaido H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria // Clin. Microbiol. Rev. 2015. V. 28. P. 337–418. https://doi.org/10.1128/CMR.00117-14
  13. Maher C., Hassan K. A. The Gram-negative permeability barrier: tipping the balance of the in and the out // mBio. 2023. V. 14. Art. e0120523. https://doi.org/10.1128/mbio.01205-23
  14. McNeil M.B., Dennison D., Parish T. Mutations in MmpL3 alter membrane potential, hydrophobicity and antibiotic susceptibility in Mycobacterium smegmatis // Microbiology (Reading). 2017. V. 163. P. 1065–1070. https://doi.org/10.1099/mic.0.000498
  15. Miller J. H. Experiments in molecular genetics. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1992. 466 p.
  16. Nesterova L. Y., Tsyganov I. V., Tkachenko A. G. Biogenic polyamines influence the antibiotic susceptibility and cell-surface properties of Mycobacterium smegmatis // Appl. Biochem. Microb. 2020. V. 56. P. 387–394. https://doi.org/10.1134/S0003683820040110
  17. Nikaido H. Molecular basis of bacterial outer membrane permeability revisited // Microbiol. Mol. Biol. Rev. 2003. V. 67. P. 593–656. https://doi.org/10.1128/MMBR.67.4.593-656.2003
  18. Nobre T. M., Martynowycz M. W., Andreev K., Kuzmenko I., Nikaido H., Gidalevitz D. Modification of Salmonella lipopolysaccharides prevents the outer membrane penetration of novobiocin // Biophys. J. 2015. V. 109. P. 2537–2545. https://doi.org/10.1016/j.bpj.2015.10.013
  19. Peloquin C. A., Davies G. R. The treatment of tuberculosis // Clin. Pharmacol. Ther. 2021. V. 110. P. 1455–1466. https://doi.org/10.1002/cpt.2261
  20. Randall L. P., Woodward M. J. The multiple antibiotic resistance (mar) locus and its significance // Res. Vet. Sci. 2002. V. 72. P. 87–93. https://doi.org/10.1053/rvsc.2001.0537
  21. Rosenberg M. Microbial adhesion to hydrocarbons: twenty-five years of doing MATH // FEMS Microbiol. Lett. 2006. V. 262. P. 129–134. https://doi.org/10.1111/j.1574-6968.2006.00291.x
  22. Samartzidou H., Delcour A. H. Excretion of endogenous cadaverine leads to a decrease in porin-mediated outer membrane permeability // J. Bacteriol. 1999. V. 181. P. 791–798. https://doi.org/10.1128/JB.181.3.791-798.1999
  23. Tkachenko A. G., Akhova A. V., Shumkov M. S., Nesterova L. Y. Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics // Res. Microbiol. 2012. V. 163. P. 83–91. https://doi.org/10.1016/j.resmic.2011.10.009
  24. Tkachenko A. G., Pozhidaeva O. N., Shumkov M. S. Role of polyamines in formation of multiple antibiotic resistance of Escherichia coli under stress conditions // Biochemistry (Moscow). 2006. V. 71. P. 1042–1049. https://doi.org/10.1134/s0006297906090148
  25. Williams K. J., Piddock L. J. Accumulation of rifampicin by Escherichia coli and Staphylococcus aureus // J. Antimicrob. Chemother. 1998. V. 42. P. 597–603. https://doi.org/10.1093/jac/42.5.597
  26. World Health Organisation. Global antimicrobial resistance and use surveillance system (GLASS) report 2022. World Health Organisation, Geneva, 2022. 72 p.

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
Жүктеу
2. Fig. 1. Effect of cadaverine on rifampicin accumulation in E. coli cells. 1 – culture of polyamine-positive strain BW25141 without additives; 2 – culture of polyamine-positive strain BW25141 grown in medium supplemented with 100 μM cadaverine; 3 – culture of polyamine-deficient strain BW25141ΔldcCΔcadA without additives; 4 – culture of polyamine-deficient strain BW25141ΔldcCΔcadA grown in medium supplemented with 100 μM cadaverine. Light columns – 2 min exposure to rifampicin, dark columns – 60 min exposure to rifampicin. *Statistically significant difference from the polyamine-positive strain grown without the addition of cadaverine; **Statistically significant difference from the polyamine-deficient strain grown without the addition of cadaverine (T-test, n ≥ 3, p ≤ 0.05).

Жүктеу (108KB)
Метадеректер
3. Fig. 2. Effect of putrescine and spermidine on rifampicin accumulation in E. coli cells. 1 – culture of polyamine-producing strain GGB2600 without additives; 2 – culture of polyamine-producing strain GGB2600 grown in medium supplemented with 100 μM putrescine; 3 – culture of polyamine-producing strain GGB2600 grown in medium supplemented with 100 μM spermidine; 4 – culture of polyamine-deficient strain SL60 without additives; 5 – culture of polyamine-deficient strain SL60 grown in medium supplemented with 100 μM putrescine. 6 – culture of polyamine-deficient strain SL60 grown in a medium supplemented with 100 μM spermidine. Light columns – 2 min exposure to rifampicin, dark columns – 60 min exposure to rifampicin. There are no statistically significant differences in the means (T-test, n ≥ 3, p ≤ 0.05).

Жүктеу (65KB)
Метадеректер
4. Fig. 3. Effect of cadaverine (a), putrescine (b) or spermidine (c) on the hydrophobicity of E. coli cells. 1 – culture of polyamine-positive strain without additives; 2 – culture of polyamine-positive strain grown in medium supplemented with 100 μM polyamine; 3 – culture of polyamine-deficient strain without additives; 4 – culture of polyamine-deficient strain grown in medium supplemented with 100 μM polyamine; a – strains BW25141 (1, 2)/BW25141ΔldcCΔcadA (3, 4); b, c – strains GGB2600 (1, 2)/SL60 (3, 4). *Statistically significant difference from the polyamine-positive strain grown without the addition of polyamine; **Statistically significant difference from the polyamine-deficient strain grown without the addition of polyamine (T-test, n ≥ 3, p ≤ 0.05).

Жүктеу (88KB)
Метадеректер
5. Fig. 4. Effect of polyamines on the expression of the marRAB operon in E. coli M2073 cells. 1 – culture without additives (dark circles); 2 – culture grown in the medium supplemented with 5 mM salicylate (open circles); 3 – culture grown in the medium supplemented with 5 mM salicylate and 1 mM putrescine (open squares); 4 – culture grown in the medium supplemented with 5 mM salicylate and 1 mM spermidine (open diamonds); 5 – culture grown in the medium supplemented with 5 mM salicylate and 1 mM cadaverine (open triangles). *Statistically significant difference from the culture grown with the addition of salicylate (2) (T-test, n ≥ 3, p ≤ 0.05).

Жүктеу (88KB)
Метадеректер

© Russian Academy of Sciences, 2025