Morphological alterations of Staphylococcus aureus caused by aryl aliphatic aminoalcohol derivative

M Dronova

Автор(и)

M Dronova State Institution «Institute of pharmacology and toxicology of National academy of medical sciences of Ukraine »,

Ключові слова:

Staphylococcus aureus, antibiotics, mechanism of action, aryl aliphatic aminoalcohols

Анотація

Increasing of antimicrobial resistance has created a critical need of the novel antimicrobial agents. One of the promising chemical classes for its development are aryl aliphatic aminoalcohols. New compounds of this class were synthesized at the Institute of organic chemistry (Kiev, Ukraine), by Y. Korotkiy. After the screening studies compound KVM-194 was selected as the potent antistaphylococcal agent. The aim of the study was to examine ultrastructural changes in the bacterial cells under the influence of the compound KVM-194.

Materials and methods.Staphylococcus aureus ATCC 25923 was used in all experiments. The minimum inhibitory concentration was determined by serial macrodilution method in Mueller-Hinton broth. Bacteria were exposed to the 0,5 MIC and 5 MICs of the KVM-194 for 1 h and 24 h. Ultrastructure of intact and treated Staphylococcus aureus cells was examined by transmission electron microscopy after contrasting by osmium tetraoxide and lead citrate.

Results and Discussion.The compound KVM-194 possesses a distinct antibacterial activity against Staphylococcus aureus, the minimum inhibitory concentration is 1.25 µg/ml. .We found that exposure to KVM-194 at a subinhibitory concentration resulted in alterations of the cell morphology even after 1 h of treatment. The roughness of the cell surface and emerging of the intracellular particles of different electron density were observed. Increase of the incubation time to 24 h led to detachment of membrane from cytoplasm, multi-membrane structures within cells emergence and formation of nonpolar septum. 1 h exposition to suprainhibitory concentration of KVM-194 resulted in nucleoid fragmentation, septum abnormalities and necrosis of some cells. We found that increasing of the incubation period to 24 h led to exacerbation of alterations: cell wall rupture, leakage of cytoplasm and a large number of lysed cells were registered.

Conclusion.Observed alterations, suggest the possible mechanism of action of KVM-194, due to its influence on the cell membrane and intracellular processes.

Посилання

Hentschke M. Combined ramR Mutation and Presence of a Tn1721-Associated tet(A) Variant in a Clinical Isolate of Salmonella enterica serovar hadar resistant to tigecycline [Text] / M. Hentschke [et al.] // Antimicrobial Agents Chemotherapy. – 2010. – Vol. 54, № 3. – Р. 1319–1322.

Steed M. E. Characterizing vancomycin-resistant Enterococcus strains with various mechanisms of daptomycin resistance developed in an in vitro pharmacokinetic/ pharmacodynamic model [Text] / M. E. Steed [et al.] // Antimicrobial Agents Chemotherapy. – 2011. – Vol. 55, № 10. – Р. 4748–4754.

Klainer A. S. Surface manifestations of antibiotic-induced alterations in protein synthesis in bacterial cells [Text] / Klainer A. S., Perkins R.L. // Antimicrobial Agents and Chemoterapy. – 1972. – Vol. 1, № 2. – P. 164–170.

Evaluation of antibiotic efficacy using electron microscopy: morphological effects of guanylureido cephalosporin, chlorobenzoylureido cephalosporin, bl-p1654, and carbenicillin on Pseudomonas aeruginosa [Text] / L. F. Ellis [et al.] // Antimicrobial Agents and Chemoterapy. – 1976. - Vol. 9, № 2. – P. 334–342.

Braga P. C. Atomic force microscopy: application to investigation of Escherichia coli morphology before and after exposure to cefodizime [Text] / P. C. Braga, D. Ricci // Antimicrobial Agents and Chemoterapy. – 1998. – Vol. 42, № 1. – P. 18–22.

Presslitz J. E. Mode of action of a structurally novel beta-lactam [Text] / J. E. Presslitz // Antimicrobial Agents and Chemoterapy. – 1978. – Vol. 14, № 1. – P. 144–150.

Lorian V. Effects of subinhibitory concentrations of antibiotics on cross walls of cocci [Text] / V. Lorian, B. Atkinson // Antimicrobial Agents and Chemoterapy. – 1976. – Vol. 9, № 6. – P. 1043–1055.

Waisbren S. J. Morphological expression of antibiotic synergism against Pseudomonas aeruginosa as observed by, scanning electron microscopy [Text] / S. J. Waisbren, D. J. Hurley, B. A. Waisbren // Antimicrobial Agents and Chemoterapy. – 1980. – Vol. 18, № 6. – P. 969–975.

Prior R. B. Morphological alterations of Pseudomonas aeruginosa by ticarcillin: a scanning electron microscope study [Text] / R. B. Prior, J. F. Warner // Antimicrobial Agents and Chemoterapy. – 1974. – Vol. 6, № 6. – P. 853–855.

DeLoney C. R. Competition of various β-lactam antibiotics for the major penicillin-binding proteins of Helicobacter pylori: antibacterial activity and effects on bacterial morphology [Text] / C. R. DeLoney, N. L. Schiller // Antimicrobial Agents and Chemoterapy. – 1999. – Vol. 43, № 11. – P. 2702–2709.

Sanyal D. An electronmicroscope study of glycopeptide antibiotic-resistant strains of Staphylococcus epidermidis [Text] / D. Sanyal, D. Greenwood // Journal of Medical Microbiology. – 1993. – Vol. 39. – P. 204–210.

Santhana Raj L. Mesosomes are a definite event in antibiotic-treated Staphylococcus aureus ATCC 25923 [Text] / L. Santhana Raj [et al.] // Tropical Biomedicine. – 2007. – Vol. 24, № 1. – P. 105–109.

New insights into the antibacterial mechanism of action of squalamine [Text] / K. Alhanout [et al.] // Journal of Antimicrobial Chemotherapy. – 2010. – Vol. 65, № 8. – P. 1688–1693.

Damage of the bacterial cell envelope by antimicrobial peptides gramicidin S and PGLa as revealed by transmission and scanning electron microscopy [Text] / M. Hartmann [et al.] // Antimicrobial Agents and Chemoterapy. – 2010. – Vol. 54, № 8. – P. 3132–3142.

Daptomycin exerts bactericidal activity without lysis of Staphylococcus aureus [Text] / N. Cotroneo [et al.] // Antimicrobial agents and chemoterapy. – 2008. – Vol. 52, № 6. – P. 2223–2225.

Scanning electron microscopy of Staphyococcus aureus and Enterococcus faecalis exposed to daptomycin [Text] / L. J. Wale [et al.] // Journal of Medical Microbiology. – 1989. – Vol. 30. – P. 45–49.

Klainer A. S. Effect of the inhibition of protein synthesis on the Escherichia coli cell envelope [Text] / A. S. Klainer, R. R. B. Russell // Antimicrobial Agents and Chemoterapy. – 1974. – Vol. 6, № 2. – P. 216–224.

Pat. № EP1098642 B1 USA, IPC A61P17/02, A61P25/28, C07D295/12 Diamino-propanol-compounds for treating ischemia / Chatterjee S. ; applicant Johns Hopkins University. – №: EP 19990937409 ; fil. 22.07.99 ; pub. 04.04.07.

Vanillylamide-based propanolamine derivative displays alpha/beta-adrenoceptor blocking and vasodilating properties [Text] / J. L. Yeh [et al.] // J. Cardiovasc. Pharmacol. – 2002. – Vol. 39, № 6. – Р. 803–813.

Vartanyan R. S. Synthesis of new aminopropanol derivatives as potencial β-adrenoblockers [Text] / R. S. Vartanyan, E. A. Adamyan, M. A. Sheyranyan // Chemical Journal of Armenia. – 2003. – Vol. 56, №3. – P. 87–91.

DiCuollo C. J. The metabolism of 3-((5-methyl-5H-as-triazino(5,6-b)-indol-3-yl)amino)-1-propanol (SK&F 21687). A potent antiviral [Text] / DiCuollo C. J., Zarembo J. E., Pagano J. F. // Xenobiotica. – 1973. – Vol. 3, № 3. – P. 171–178.

Antioxidant and antiradical properties of new aminoacid derivatives of aminoalcohols [Text] / M. H. Malakyan [et al.] // Khimiko-Farmatsevticheskii Zhurnal. – 2010. –Vol. 44. № 8. – P. 19–21.

Pat. 20110118210 USA, IPC A61 K 31/675 Aminopropanol derivatives [Text] / Rainer A., Francotte E., Zecri F., Zollinger M. – № US 2011/0118210 A1 ; fil. 28.01.11 ; pub. 19.05.2011.

Pat. 7625950 USA, IPC C07C 217/72 Amino-propanol derivatives as sphingosine-1-phosphate receptor modulator [Text] / Klaus H., Carsten S., Zecri F. ; applicant Novartis AG. – № US 10/554556 ; fil. 29.03.2004 ; pub. 01.12.2009.

Pat. 23451 UA, IPC С07С217/28 Agent for treating memory disorders [Text] / Zaycev L. M., Korotkiy Y. V, Кrasavtsev І. І., Losinskiy М. О., Khromova І. V., Seredenin S. B., Voronina Т. А. ; applicant Institute of organic chemistry NAS of Ukraine. – № 94063487 ; fil. 16.06.1994 ; pub. 29.12.1999, Bul. № 8, 1999.

Pat. WO 2007/058639 WO, IPC A61K31/135, A61K31/785, A01N33/02 Antibacterial agents [Text] / Yerramilli V. S. N. M. ; applicant Idexx Laboratories Inc. – № PCT/US2005/029602 ; fil. 23.08.2005 ; pub. 24.05.2007.

Piperazine propanol derivative as a novel antifungal targeting 1,3-beta-D-glucan synthase [Text] / O. Kondoh [et al.] // Biol. Pharm. Bull. – 2005. – Vol. 28, № 11. – Р. 2138–2141.

Pat. 4361557 USA, IPC A61K31/22, C07C233/16 1-Aryl-2-acylamido-3-fluoro-1-propanol acylates, methods for their use as anti-bacterial agents and compositions useful therefore [Text] / Nagabbusha T. L. ; applicant Schering Corporation. – № US 291/663 ; fil. 10.08.1981 ; pub. 30.11.1982.

Guidelines for Susceptibility Testing of Microorganisms to Antibacterial Agents 4.2.1890-04 [Text] // Clinical Microbiology and Antimicrobial Chemotherapy. – 2004. – Vol. 6, № 4. – P. 306 – 359.