{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:49:26Z","timestamp":1788954566482,"version":"build-2803163510"},"reference-count":24,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005643","name":"Uniwersytet \u0141\u00f3dzki","doi-asserted-by":"publisher","award":["B1811000001836.02"],"award-info":[{"award-number":["B1811000001836.02"]}],"id":[{"id":"10.13039\/501100005643","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Staphylococcus aureus infections are common and difficult to treat. The increasing number of drug-resistant staphylococcal infections has created the need to develop new strategies for the treatment of these infections. The synergistic antimicrobial activity of different pharmaceuticals seems to be an interesting alternative. The aim of this study was to assess the synergistic activity of ciprofloxacin and carvedilol against S. aureus strains. The antibacterial potential of ciprofloxacin and carvedilol was evaluated according to the CLSI guidelines. The calcium content in S. aureus cells was measured using flow cytometry and atomic absorption spectroscopy. Moreover, confocal and scanning electron microscopy were used to determine the mechanism of antibacterial synergy of ciprofloxacin and carvedilol. The antibacterial effect of ciprofloxacin was higher in the presence of carvedilol than in S. aureus cultures containing the antibiotic only. A significant increase in S. aureus membrane permeability was also observed. The simultaneous administration of the tested compounds caused damage to S. aureus cells visualized by SEM. Enhancement of the antimicrobial action of ciprofloxacin by carvedilol was correlated with an increase in free calcium content in S. aureus cells, morphological changes to the cells, and a reduction in the ability to form bacterial aggregates.<\/jats:p>","DOI":"10.3390\/molecules24224104","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T10:56:34Z","timestamp":1573728994000},"page":"4104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The Synergy of Ciprofloxacin and Carvedilol against Staphylococcus aureus\u2013Prospects of a New Treatment Strategy?"],"prefix":"10.3390","volume":"24","author":[{"given":"Katarzyna","family":"Zawadzka","sequence":"first","affiliation":[{"name":"Department of Industrial Microbiology and Biotechnology, Faculty of Biology and Environmental Protection, University of Lodz, 12\/16 Banacha Street, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Industrial Microbiology and Biotechnology, Faculty of Biology and Environmental Protection, University of Lodz, 12\/16 Banacha Street, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6505-3088","authenticated-orcid":false,"given":"Ireneusz","family":"Piwo\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Materials Technology and Chemistry, Faculty of Chemistry, University of Lodz, 163 Pomorska Street, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Lisowska","sequence":"additional","affiliation":[{"name":"Department of Industrial Microbiology and Biotechnology, Faculty of Biology and Environmental Protection, University of Lodz, 12\/16 Banacha Street, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1128\/IAI.01216-13","article-title":"Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus","volume":"82","author":"Pollitt","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pollitt, E.J.G., Szkuta, P.T., Burns, N., and Foster, S.J. (2018). Staphylococcus aureus infection dynamics. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007112"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/femsre\/fux007","article-title":"Antibiotic resistance in Staphylococcus aureus. Current status and future prospects","volume":"41","author":"Foster","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/ddr.21523","article-title":"Transcriptome analysis predicts mode of action of benzimidazole molecules against Staphylococcus aureus UAMS-1","volume":"80","author":"Chauhan","year":"2019","journal-title":"Drug Dev. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.bioorg.2018.11.007","article-title":"Synthesis and evaluation of new 4-oxoquinazolin-3(4H)-yl)benzoic acid and benzamide derivatives as potent antibacterial agents effective against multidrug resistant Staphylococcus aureus","volume":"83","author":"Gatadi","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.ejmech.2018.08.070","article-title":"Synthesis of 1,2,3-triazole linked 4(3H)-Quinazolinones as potent antibacterial agents against multidrug-resistant Staphylococcus aureus","volume":"5","author":"Gatadi","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7237","DOI":"10.1038\/s41598-018-25714-z","article-title":"Synergistic combination of two antimicrobial agents closing each other\u2019s mutant selection windows to prevent antimicrobial resistance","volume":"8","author":"Xu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ijantimicag.2017.12.014","article-title":"Antibacterial activity of high concentrations of carvedilol against Gram-positive and Gram-negative bacteria","volume":"51","author":"Zawadzka","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1078\/0944-5013-00204","article-title":"Antimicrobial potentiality of a new non-antibiotic: The cardiovascular drug oxyfedrine hydrochloride","volume":"158","author":"Mazumdar","year":"2003","journal-title":"Microbiol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9379","DOI":"10.1039\/C5RA27175D","article-title":"Synthesis and biological evaluation of novel carbazolyl glyoxamides as anticancer and antibacterial agents","volume":"6","author":"Tantak","year":"2016","journal-title":"RSC Adv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.bmcl.2018.03.033","article-title":"Synthesis and investigations into the anticancer and antibacterial activity studies of \u03b2-carboline chalcones and their bromide salts","volume":"28","author":"Hridhay","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1365-2958.2004.04276.x","article-title":"Calcium signalling in bacteria","volume":"54","author":"Dominguez","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1254\/jphs.13020FP","article-title":"Effects of the fluoroquinolone antibacterial drug ciprofloxacin on ventricular repolarization in the halothane-anesthetized Guinea pig","volume":"122","author":"Matsuo","year":"2013","journal-title":"J. Pharmacol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.redox.2015.08.010","article-title":"Calcium and ROS: A mutual interplay","volume":"6","author":"Bertram","year":"2015","journal-title":"Redox Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e41075","DOI":"10.1371\/journal.pone.0041075","article-title":"Planktonic Aggregates of Staphylococcus aureus Protect against Common Antibiotics","volume":"7","author":"Haaber","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Das, T., Sehar, S., Koop, L., Wong, Y.K., Ahmed, S., Siddiqui, K.S., and Manefield, M. (2014). Influence of Calcium in Extracellular DNA Mediated Bacterial Aggregation and Biofilm Formation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091935"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.micpath.2013.05.002","article-title":"Biofilm formation and dispersal of Staphylococcus aureus under the influence of oxacillin","volume":"61\u201362","author":"Mirani","year":"2013","journal-title":"Microbial. Pathog."},{"key":"ref_19","first-page":"71","article-title":"Enzymatic degradation of in vitro Staphylococcus aureus biofilms supplemented with human plasma","volume":"9","author":"Watters","year":"2016","journal-title":"Infect. Drug Resist."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/2049-632X.12158","article-title":"Temporal expression of agrB, cidA, and alsS in the early development of Staphylococcus aureus UAMS-1 biofilm formation and the structural role of extracellular DNA and carbohydrates","volume":"70","author":"Grande","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.35248\/2167-1052.19.8.226","article-title":"Tendon Rupture as a probable side effect of Ciprofloxacin: A review article","volume":"8","author":"Foroutan","year":"2019","journal-title":"Adv. Pharmacoepidemiol. Drug Saf."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9625","DOI":"10.1093\/nar\/gky793","article-title":"Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2","volume":"46","author":"Hangas","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1002\/hep.23689","article-title":"Carvedilol for portal hypertension in patients with cirrhosis","volume":"51","author":"Bosch","year":"2010","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ijantimicag.2014.10.020","article-title":"Determination of in vitro synergy for dual antimicrobial therapy against resistant Neisseria gonorrhoeae using Etest and agar dilution","volume":"45","author":"Wind","year":"2015","journal-title":"Int. J. Antimicrob. Agents"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/22\/4104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:34:15Z","timestamp":1760189655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/22\/4104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,14]]},"references-count":24,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["molecules24224104"],"URL":"https:\/\/doi.org\/10.3390\/molecules24224104","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,14]]}}}