Thioridazine affects transcription of genes involved in cell wall biosynthesis in methicillin-resistant Staphylococcus aureus: Thioridazine affects cell wall biosynthesis genes in MRSA
Abstract
The antipsychotic drug thioridazine is a candidate drug for an alternative treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in combination with the β-lactam antibiotic oxacillin. The drug has been shown to have the capability to resensitize MRSA to oxacillin. We have previously shown that the expression of some resistance genes is abolished after treatment with thioridazine and oxacillin. To further understand the mechanism underlying the reversal of resistance, we tested the expression of genes involved in antibiotic resistance and cell wall biosynthesis in response to thioridazine in combination with oxacillin. We observed that the oxacillin-induced expression of genes belonging to the VraSR regulon is reduced by the addition of thioridazine. The exclusion of such key factors involved in cell wall biosynthesis will most likely lead to a weakened cell wall and affect the ability of the bacteria to sustain oxacillin treatment. Furthermore, we found that thioridazine itself reduces the expression level of selected virulence genes and that selected toxin genes are not induced by thioridazine. In the present study, we find indications that the mechanism underlying reversal of resistance by thioridazine relies on decreased expression of specific genes involved in cell wall biosynthesis.
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TCAs act by repressing the expression of β-lactam resistance genes, while thioridazine acts by inhibiting the expression of genes involved in cell wall biosynthesis.
“It has been reported that do so, TCAs act by repressing the expression of β-lactam resistance genes, while thioridazine acts by inhibiting the expression of genes involved in cell wall biosynthesis [98,99].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [99]
Cites
Antibiotics for Emerging Pathogens
Fischbach, M. A., & Walsh, C. T. (2009) · Science · doi:10.1126/science.1176667 · Cited by 1,787 · see citing works
Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule.
Novick, R. P., Ross, H. F., Projan, S. J., Kornblum, J. S., Kreiswirth, B. N., & Moghazeh, S. L. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06074.x · Cited by 1,071 · see citing works
Queck, S. Y., Jameson‐Lee, M., Villaruz, A. E., Bach, T. L., Khan, B. A., Sturdevant, D. E., Ricklefs, S., Li, M., & Otto, M. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.08.005 · Cited by 596 · see citing works
Moazed, D., Stern, S., & Noller, H. F. (1986) · Journal of Molecular Biology · doi:10.1016/0022-2836(86)90441-9 · Cited by 544 · see citing works
Kuroda, M., Kuroda, H., Oshima, T., Takeuchi, F., Mori, H., & Hiramatsu, K. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03599.x · Cited by 515 · see citing works
Morfeldt, E., Taylor, D., von Gabain, A., & Arvidson, S. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00136.x · Cited by 476 · see citing works
Pinho, M. G., de LENCASTRE, H., & Tomasz, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191260798 · Cited by 392 · see citing works
Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression
Huntzinger, E., Boisset, S., Saveanu, C., Benito, Y., Geissmann, T., Namane, A., Lina, G., Étienne, J., Ehresmann, B., Ehresmann, C., et al. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600572 · Cited by 362 · see citing works
Utaida, S., Dunman, P. M., Macapagal, D., Murphy, E., Projan, S. J., Singh, V. K., Jayaswal, R. K., & Wilkinson, B. J. (2003) · Microbiology · doi:10.1099/mic.0.26426-0 · Cited by 328 · see citing works
Global Regulation of Staphylococcus aureus Genes by Rot
Saïd‐Salim, B., Dunman, P. M., McAleese, F., Macapagal, D., Murphy, E., McNamara, P. J., Arvidson, S., Foster, T. J., Projan, S. J., & Kreiswirth, B. N. (2003) · Journal of Bacteriology · doi:10.1128/jb.185.2.610-619.2003 · Cited by 286 · see citing works
Inhibition of rot translation by RNAIII, a key feature of agr function
Geisinger, E., Adhikari, R. P., Jin, R., Ross, H. F., & Novick, R. P. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05292.x · Cited by 252 · see citing works
Phenothiazines and Thioxanthenes Inhibit Multidrug Efflux Pump Activity in Staphylococcus aureus
Kaatz, G. W., Moudgal, V. V., Seo, S. M., & Kristiansen, J. E. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.2.719-726.2003 · Cited by 225 · see citing works
Oates, J. A., Wood, A. J. J., Donowitz, G. R., & Mandell, G. L. (1988) · New England Journal of Medicine · doi:10.1056/nejm198802253180806 · Cited by 208 · see citing works
Stranden, A., Kerstin Ehlert, B., Labischinski, H., & Berger‐Bächi, B. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.1.9-16.1997 · Cited by 201 · see citing works
McAleese, F., Wu, S. W., Sieradzki, K., Dunman, P. M., Murphy, E., Projan, S. J., & Tomasz, A. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.3.1120-1133.2006 · Cited by 196 · see citing works
Łęski, T. A., & Tomasz, A. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.5.1815-1824.2005 · Cited by 184 · see citing works
Vandenesch, F., Kornblum, J. S., & Novick, R. P. (1991) · Journal of Bacteriology · doi:10.1128/jb.173.20.6313-6320.1991 · Cited by 183 · see citing works
Memmi, G., Filipe, S. R., Pinho, M. G., Fu, Z., & Cheung, A. L. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00049-08 · Cited by 170 · see citing works
Efflux-mediated response of Staphylococcus aureus exposed to ethidium bromide
Couto, I., Costa, S. S., Viveiros, M., Martins, M., & Amaral, L. (2008) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkn217 · Cited by 160 · see citing works
Nielsen, J. S., Lei, L. K., Ebersbach, T., Olsen, A. S., Klitgaard, J. K., Valentin‐Hansen, P., & Kallipolitis, B. H. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1081 · Cited by 143 · see citing works
Self-citationKozarich, J. W., & Strominger, J. L. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38141-3 · Cited by 137 · see citing works
Saravia‐Otten, P., Müller, H. P., & Arvidson, S. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.17.5259-5263.1997 · Cited by 122 · see citing works
Antimicrobial activity of phenothiazines.
Amaral, L., Viveiros, M., & Molnar, J. A. (2004) · PubMed · Cited by 121 · see citing works
Ziebandt, A., Becher, D., Ohlsen, K., Hacker, J. H., Hecker, M., & Engelmann, S. (2004) · PROTEOMICS · doi:10.1002/pmic.200400937 · Cited by 120 · see citing works
Pietiäinen, M., François, P., Hyyryläinen, H., Tangomo, M., Sass, V., Sahl, H., Schrenzel, J., & Kontinen, V. P. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-429 · Cited by 112 · see citing works
Dutta, N. K., Mehra, S., & Kaushal, D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010069 · Cited by 103 · see citing works
Truong, Q. C., & Hooper, D. C. (2007) · Journal of Bacteriology · doi:10.1128/jb.01819-06 · Cited by 101 · see citing works
Blake, K. L., O’Neill, A. J., Mengin‐Lecreulx, D., Henderson, P. J. F., Bostock, J. M., Dunsmore, C. J., Simmons, K. J., Fishwick, C. W. G., Leeds, J. A., & Chopra, I. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06648.x · Cited by 85 · see citing works
Fujimoto, D. F., & Bayles, K. W. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.14.3724-3726.1998 · Cited by 83 · see citing works
Bernal, P., Lemaire, S., Pinho, M. G., Mobashery, S., Hinds, J., & Taylor, P. W. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.114793 · Cited by 71 · see citing works
Kristiansen, M. (2003) · International Journal of Antimicrobial Agents · doi:10.1016/s0924-8579(03)00200-0 · Cited by 68 · see citing works
Reversal of methicillin resistance in Staphylococcus aureus by thioridazine
Klitgaard, J. K., Skov, M. N., Kallipolitis, B. H., & Kolmos, H. J. (2008) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkn417 · Cited by 66 · see citing works
Self-citationStrain dependence of the cell wall-damage induced stimulon in Staphylococcus aureus
McCallum, N., Spehar, G., Bischoff, M., & Berger‐Bächi, B. (2006) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2006.06.008 · Cited by 63 · see citing works
Impact ofsarandagron methicillin resistance inStaphylococcus aureus
Durán, S. P., Kayser, F. H., & Berger‐Bächi, B. (1996) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1996.tb08394.x · Cited by 52 · see citing works
Substrate analogues to study cell-wall biosynthesis and its inhibition
Lazar, K. L., & Walker, S. (2002) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(02)00355-1 · Cited by 47 · see citing works
Diversity of Penicillin-binding Proteins
Xin, F., Liu, Y., Smith, D. G. S., Konermann, L., Siu, K. W. M., & Golemi, D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706296200 · Cited by 46 · see citing works
Kristiansen, J. E. (1979) · Acta Pathologica Microbiologica Scandinavica Section B Microbiology · doi:10.1111/j.1699-0463.1979.tb02445.x · Cited by 43 · see citing works
Hendricks, O. (2003) · International Journal of Antimicrobial Agents · doi:10.1016/s0924-8579(03)00205-x · Cited by 41 · see citing works
Martins, M., Bleiß, W., Marko, A., Ordway, D. J., Viveiros, M., Leandro, C., Pacheco, T., Molnar, J. A., Kristiansen, J. E., & Amaral, L. (2004) · PubMed · Cited by 36 · see citing works
The AbcA Transporter of Staphylococcus aureus Affects Cell Autolysis
Schrader‐Fischer, G., & Berger‐Bächi, B. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.2.407-412.2001 · Cited by 32 · see citing works
Transcription analysis of the Staphylococcus aureus gene encoding penicillin-binding protein 4
Domanski, T. L., DeJonge, B. L. M., & Bayles, K. W. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.8.2651-2657.1997 · Cited by 26 · see citing works
Effect of Disruption of Staphylococcus aureus PBP4 Gene on Resistance to β-Lactam Antibiotics
Katayama, Y., Zhang, H.-Z., & Chambers, H. F. “. (2003) · Microbial Drug Resistance · doi:10.1089/107662903322762752 · Cited by 25 · see citing works
The Cell Wall Stress Stimulon of Staphylococcus aureus and Other Gram- Positive Bacteria
Wilkinson, B. J., Muthaiyan, A., & Jayaswal, R. K. (2005) · Anti-Infective Agents · doi:10.2174/1568012054368119 · Cited by 25 · see citing works
Stolze, K., & Mason, R. P. (1991) · Chemico-Biological Interactions · doi:10.1016/0009-2797(91)90037-8 · Cited by 16 · see citing works
Thioridazine induces erythrocyte stomatocytosis due to interactions with negatively charged lipids.
Hendrich, A. B., Lichacz, K., Burek, A., & Michalak, K. (2002) · PubMed · Cited by 16 · see citing works
In vitro antimicrobial activity of 18 phenothiazine derivatives: structure-activity relationship.
Bourlioux, P., Moreaux, J. M., Su, W. J., & Boureau, H. (1992) · PubMed · Cited by 14 · see citing works
Hadji‐nejad, S., Rahbar, H., & Mehrgan, H. (2010) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v9i3.56284 · Cited by 12 · see citing works
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Worthington, R. J., & Melander, C. (2013) · Trends in Biotechnology · doi:10.1016/j.tibtech.2012.12.006 · Cited by 625 · see citing works
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Alav, I., Sutton, J. M., & Rahman, K. M. (2018) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dky042 · Cited by 504 · see citing works
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Bem, A. E., Velikova, N., Pellicer, M. T., van Baarlen, P., Marina, A., & Wells, J. M. (2014) · ACS Chemical Biology · doi:10.1021/cb5007135 · Cited by 203 · see citing works
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Worthington, R. J., & Melander, C. (2013) · The Journal of Organic Chemistry · doi:10.1021/jo400236f · Cited by 196 · see citing works
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AlMatar, M., Albarri, O., Makky, E. A., & Köksal, F. (2020) · Pharmacological Reports · doi:10.1007/s43440-020-00160-9 · Cited by 92 · see citing works
Worthington, R. J., Blackledge, M. S., & Melander, C. (2013) · Future Medicinal Chemistry · doi:10.4155/fmc.13.58 · Cited by 90 · see citing works
Mun, S., Joung, D.-K., Kim, S., Park, S., Seo, Y., Gong, R., Choi, J., Shin, D.-W., Rho, J., Kang, O., et al. (2014) · Foodborne Pathogens and Disease · doi:10.1089/fpd.2013.1627 · Cited by 64 · see citing works
Thorsing, M., Klitgaard, J. K., Atilano, M. L., Skov, M. N., Kolmos, H. J., Filipe, S. R., & Kallipolitis, B. H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064518 · Cited by 57 · see citing works
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Dutta, N. K., Mazumdar, K., Dastidar, S. G., Karakousis, P. C., & Amaral, L. (2011) · Recent Patents on Anti-Infective Drug Discovery · doi:10.2174/157489111796064597 · Cited by 35 · see citing works
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Marchi, E., Furi, L., Arioli, S., Morrissey, I., Lorenzo, V. D., Mora, D., Giovannetti, L., Oggioni, M. R., & Viti, C. (2014) · Microbiological Research · doi:10.1016/j.micres.2014.07.001 · Cited by 30 · see citing works
Poulsen, M. Ø., Jacobsen, K., Thorsing, M., Kristensen, N. R. D., Clasen, J., Lillebæk, E. M. S., Skov, M. N., Kallipolitis, B. H., Kolmos, H. J., & Klitgaard, J. K. (2012) · Research in Microbiology · doi:10.1016/j.resmic.2012.10.007 · Cited by 27 · see citing works
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Stenger, M., Klein, K., Grønnemose, R. B., Klitgaard, J. K., Kolmos, H. J., Lindholt, J. S., Alm, M., Thomsen, P., & Andersen, T. E. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.09.018 · Cited by 26 · see citing works
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Stenger, M., Hendel, K., Bollen, P. J. A., Licht, P. B., Kolmos, H. J., & Klitgaard, J. K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135571 · Cited by 16 · see citing works
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- Authors
- Bonde, M., Højland, D. H., Kolmos, H. J., Kallipolitis, B. H., & Klitgaard, J. K.
- Affiliations
- University of Southern Denmark (DK)
- Corresponding author
- Klitgaard, Janne K.
- Venue
- FEMS Microbiology Letters
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-25
- Volume
- 318
- Issue
- 2
- Pages
- 168-176
- ISSN
- 0378-1097 (ISSN-L)
- OpenAlex
- W1524280827
- Cited by
- 34
- References
- 47
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2022: 3 · 2021: 1 · 2020: 2 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 1 · 2014: 4 · 2013: 4 · 2012: 2
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEMS Microbiology Letters (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Funders
- Lundbeckfonden (R32-2008-2819)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- thioridazine, methicillin-resistant Staphylococcus aureus, oxacillin, antibiotic resistance reversal, cell wall biosynthesis, gene expression, virulence genes, toxin genes, combination therapy
- MeSH terms
- Anti-Bacterial Agents, Bacterial Proteins, Cell Wall, Oxacillin, Thioridazine, Transcription, Genetic, Gene Expression Regulation, Bacterial, Methicillin-Resistant Staphylococcus aureus
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