{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:20:06Z","timestamp":1791260406835,"version":"4.1.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    leads to diverse infections, and their treatment relies on the use of antibiotics. Nevertheless, the rise of antibiotic resistance poses an escalating challenge and various mechanisms contribute to antibiotic resistance, including modifications to drug targets, enzymatic deactivation of drugs, and increased efflux of antibiotics. Hence, the quest for innovative antimicrobial solutions has intensified in the face of escalating antibiotic resistance and the looming threat of superbugs. The NorA protein of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    , classified as an efflux pump within the major facilitator superfamily, when overexpressed, extrudes various substances, including fluoroquinolones (such as ciprofloxacin) and quaternary ammonium. Addressing this, the unexplored realm of inorganic and organometallic compounds in medicinal chemistry holds promise. Notably, the study focused on investigating two different series of palladium-based metal complexes consisting of QSL_P\n                    <jats:sup>A<\/jats:sup>\n                    and QSL_P\n                    <jats:sup>B<\/jats:sup>\n                    ligands to identify a potent NorA efflux pump inhibitor that can restore the susceptibility to fluoroquinolone antibiotics. QSL_Pd\n                    <jats:sup>5A<\/jats:sup>\n                    was identified as a potent efflux pump inhibitor from the real-time efflux assay. QSL_Pd\n                    <jats:sup>5A<\/jats:sup>\n                    also resensitized SA1199B to ciprofloxacin at a low concentration of 0.125 \u00b5g\/mL without elucidating cytotoxicity on the NRK-62E cell line. The\n                    <jats:italic>in vitro<\/jats:italic>\n                    findings were substantiated by docking results, indicating favorable interactions between QSL_Pd\n                    <jats:sup>5A<\/jats:sup>\n                    and the NorA efflux pump.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2023.1340135","type":"journal-article","created":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T23:36:15Z","timestamp":1705275375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Effect of palladium(II) complexes on NorA efflux pump inhibition and resensitization of fluoroquinolone-resistant Staphylococcus aureus: in vitro and in silico approach"],"prefix":"10.3389","volume":"13","author":[{"given":"Rajaramon","family":"Shobana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaffer Hussain","family":"Thahirunnisa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selvam","family":"Sivaprakash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlin Jose","family":"Amali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adline Princy","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devarajan","family":"Suresh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.2147\/IDR.S201124","article-title":"A novel mechanism of action of ketoconazole: inhibition of the NorA efflux pump system and biofilm formation in multidrug-resistant Staphylococcus aureus","volume":"12","author":"Abd El-Baky","year":"2019","journal-title":"Infection Drug Resistance"},{"key":"B2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.4236\/jbpc.2017.82002","article-title":"Synthesis and antibacterial studies of metal complexes of cu(II), ni(II) and co(II) with tetradentate ligand","volume":"8","author":"Abdulkarem","year":"2017","journal-title":"J. Biophys. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1093\/jac\/dky042","article-title":"Role of bacterial efflux pumps in biofilm formation","volume":"73","author":"Alav","year":"2018","journal-title":"J. Antimicrobial Chemotherapy"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8100405","article-title":"Tackling antibiotic resistance with compounds of natural origin: A comprehensive review","volume":"8","author":"\u00c1lvarez-Mart\u00ednez","year":"2020","journal-title":"Biomedicines"},{"key":"B5","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.resmic.2017.11.001","article-title":"The hydrophobic trap\u2014the Achilles heel of RND efflux pumps","volume":"169","author":"Aron","year":"2018","journal-title":"Res. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01290","article-title":"Staphylococcus aureus quorum regulator sarA targeted compound, 2-[(Methylamino)methyl]phenol inhibits biofilm and down-regulates virulence genes","volume":"8","author":"Balamurugan","year":"2017","journal-title":"Front. Microbiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/nrmicro2200","article-title":"Waves of resistance: Staphylococcus aureus in the antibiotic era","volume":"7","author":"Chambers","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1111\/1469-0691.12705","article-title":"New epidemiology of Staphylococcus aureus infection in Asia","volume":"20","author":"Chen","year":"2014","journal-title":"Clin. Microbiol. Infection"},{"key":"B9","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1080\/21505594.2021.1878688","article-title":"Pathogenicity and virulence of Staphylococcus aureu","volume":"12","author":"Cheung","year":"2021","journal-title":"Virulence"},{"key":"B10","doi-asserted-by":"publisher","first-page":"849","DOI":"10.3390\/chemistry2040056","article-title":"New antimicrobial strategies based on metal complexes","volume":"2","author":"Claudel","year":"2020","journal-title":"Chemistry"},{"key":"B11","doi-asserted-by":"publisher","first-page":"83","DOI":"10.3390\/antibiotics2010083","article-title":"Resistance to antimicrobials mediated by efflux pumps in staphylococcus aureus","volume":"2","author":"Costa","year":"2013","journal-title":"Antibiotics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"59","DOI":"10.2174\/1874285801307010059","article-title":"Multidrug efflux pumps in staphylococcus aureus: an update","volume":"7","author":"Costa","year":"2013","journal-title":"Open Microbiol. J."},{"key":"B13","doi-asserted-by":"publisher","first-page":"21318","DOI":"10.1039\/D0NJ03122D","article-title":"Biphosphinic ruthenium complexes as the promising antimicrobial agents","volume":"44","author":"de Sousa","year":"2020","journal-title":"New J. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s10863-021-09906-3","article-title":"Effect of Carvacrol and Thymol on NorA efflux pump inhibition in multidrug-resistant (MDR) Staphylococcus aureus strains","volume":"53","author":"dos Santos Barbosa","year":"2021","journal-title":"J. Bioenergetics Biomembranes"},{"key":"B15","doi-asserted-by":"publisher","first-page":"4071","DOI":"10.1021\/acs.organomet.7b00605","article-title":"Toxicity of metal compounds: knowledge and myths","volume":"36","author":"Egorova","year":"2017","journal-title":"Organometallics"},{"key":"B16","doi-asserted-by":"publisher","first-page":"9799","DOI":"10.1021\/acsanm.1c02208","article-title":"Cocktail of CuO, ZnO, or CuZn Nanoparticles and Antibiotics for Combating Multidrug-Resistant Pseudomonas aeruginosa via Efflux Pump Inhibition","volume":"4","author":"Eleftheriadou","year":"2021","journal-title":"ACS Appl. Nano Materials"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2020.127670","article-title":"Inhibition of the NorA efflux pump of S. aureus by (Z)-5-(4-Fluorobenzylidene)-Imidazolidines","volume":"31","author":"Faillace","year":"2021","journal-title":"Bioorganic Medicinal Chem. Lett."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114656","article-title":"New C-6 functionalized quinoline NorA inhibitors strongly synergize with ciprofloxacin against planktonic and biofilm growing resistant Staphylococcus aureus strains","volume":"241","author":"Felicetti","year":"2022","journal-title":"Eur. J. Medicinal Chem."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9020090","article-title":"Metal complexes, an untapped source of antibiotic potential","volume":"9","author":"Frei","year":"2020","journal-title":"Antibiotics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/s41570-023-00463-4","article-title":"Metals to combat antimicrobial resistance","volume":"7","author":"Frei","year":"2023","journal-title":"Nat. Rev. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1002\/2211-5463.13381","article-title":"Metallodrugs: an approach against invasion and metastasis in cancer treatment","volume":"12","author":"Gonz\u00e1lez-Ballesteros","year":"2022","journal-title":"FEBS Open Bio"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1016\/S0140-6736(22)02185-7","article-title":"Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"400","author":"Ikuta","year":"2022","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1093\/jac\/dks232","article-title":"Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus","volume":"67","author":"Kalia","year":"2012","journal-title":"J. Antimicrobial Chemotherapy"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9100649","article-title":"Benzoxazole-based metal complexes to reverse multidrug resistance in bacteria","volume":"9","author":"Kincses","year":"2020","journal-title":"Antibiotics"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113696","article-title":"Discovery of metal-based complexes as promising antimicrobial agents","volume":"224","author":"Liang","year":"2021","journal-title":"Eur. J. Medicinal Chem."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-4399(01)88009-0","article-title":"M100-S11, Performance standards for antimicrobial susceptibility testing","volume":"23","author":"Limbago","year":"2001","journal-title":"Clin. Microbiol. Newslett"},{"key":"B27","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1002\/anie.200461471","article-title":"The composition of ehrlich\u2019s salvarsan: resolution of a century-old debate","volume":"44","author":"Lloyd","year":"2005","journal-title":"Angewandte Chemie Int. Edition"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/Spectrum.00951-21","article-title":"Repurposing approved drugs as fluoroquinolone potentiators to overcome efflux pump resistance in staphylococcus aureus","volume":"9","author":"Mahey","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10101310","article-title":"Bacterial antibiotic resistance: the most critical pathogens","volume":"10","author":"Mancuso","year":"2021","journal-title":"Pathogens"},{"key":"B30","doi-asserted-by":"publisher","first-page":"72","DOI":"10.2174\/1874285801307010072","article-title":"A simple method for assessment of MDR bacteria for over-expressed efflux pumps","volume":"7","author":"Martins","year":"2013","journal-title":"Open Microbiol. J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"418","DOI":"10.3390\/chemistry2020026","article-title":"Recent studies on the antimicrobial activity of transition metal complexes of groups 6\u201312","volume":"2","author":"Nasiri Sovari","year":"2020","journal-title":"Chemistry"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/4657396","article-title":"Biofilm formation by methicillin-resistant and methicillin-sensitive staphylococcus aureus strains from hospitalized patients in Poland","volume":"2018","author":"Piechota","year":"2018","journal-title":"BioMed. Res. Int."},{"key":"B33","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1179\/2047773215Y.0000000030","article-title":"Antimicrobial resistance: a global multifaceted phenomenon","volume":"109","author":"Prestinaci","year":"2015","journal-title":"Pathog. Global Health"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1139026","article-title":"Multi-functional approach in the design of smart surfaces to mitigate bacterial infections: a review","volume":"13","author":"Rajaramon","year":"2023","journal-title":"Front. Cell. Infection Microbiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"37007","DOI":"10.1039\/C7RA03859C","article-title":"Investigation on the effect of known potent S. aureus NorA efflux pump inhibitors on the staphylococcal biofilm formation","volume":"7","author":"Sabatini","year":"2017","journal-title":"RSC Adv."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.drup.2016.04.003","article-title":"Multidrug efflux pumps of Gram-positive bacteria","volume":"27","author":"Schindler","year":"2016","journal-title":"Drug Resistance Updates"},{"key":"B37","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1517\/17460441.2012.688949","article-title":"Understanding efflux in Gram-negative bacteria: opportunities for drug discovery","volume":"7","author":"Schweizer","year":"2012","journal-title":"Expert Opin. Drug Discovery"},{"key":"B38","doi-asserted-by":"publisher","first-page":"129","DOI":"10.4103\/ijmr.IJMR_2079_17","article-title":"Efflux pump inhibitors for bacterial pathogens: From bench to bedside","volume":"149","author":"Sharma","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/6819080","article-title":"Antimicrobial agents based on metal complexes: present situation and future prospects","volume":"2022","author":"Sharma","year":"2022","journal-title":"Int. J. Biomaterials"},{"key":"B40","doi-asserted-by":"publisher","first-page":"105","DOI":"10.2217\/14622416.9.1.105","article-title":"ABC multidrug transporters: structure, function and role in chemoresistance","volume":"9","author":"Sharom","year":"2008","journal-title":"Pharmacogenomics"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02990","article-title":"Inhibiting bacterial drug efflux pumps via phyto-therapeutics to combat threatening antimicrobial resistance","volume":"9","author":"Shriram","year":"2018","journal-title":"Front. Microbiol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01868","article-title":"Boeravinone B, A novel dual inhibitor of norA bacterial efflux pump of staphylococcus aureus and human P-glycoprotein, reduces the biofilm formation and intracellular invasion of bacteria","volume":"8","author":"Singh","year":"2017","journal-title":"Front. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.19080\/CTOIJ.2019.14.555883","article-title":"Metal complexes in medicine: an overview and update from drug design perspective","volume":"14","author":"Sodhi","year":"2019","journal-title":"Cancer Ther. Oncol. Int. J."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.700198","article-title":"Development of an antibiotic resistance breaker to resensitize drug-resistant staphylococcus aureus: in silico and in vitro approach","volume":"11","author":"Thamilselvan","year":"2021","journal-title":"Front. Cell. Infection Microbiol."},{"key":"B45","doi-asserted-by":"crossref","DOI":"10.1159\/000517082","article-title":"Secondary metabolites governing microbiome interaction of staphylococcal pathogens and commensals","volume":"31","author":"Torres Salazar","year":"2021","journal-title":"Microbial. Physiol"},{"key":"B46","doi-asserted-by":"crossref","first-page":"421","DOI":"10.3389\/fcimb.2020.00421","article-title":"Reciprocal cooperation of type a procyanidin and nitrofurantoin against multi-drug resistant (mdr) upec: A ph-dependent study","volume":"10","author":"Vasudevan","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B47","first-page":"1","article-title":"Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics 2017","year":"2017"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1002\/ejic.201600908","article-title":"Redox-active metal complexes for anticancer therapy","volume":"2017","author":"Zhang","year":"2017","journal-title":"Eur. J. Inorganic Chem."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1340135\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T23:36:29Z","timestamp":1705275389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1340135\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,15]]},"references-count":48,"alternative-id":["10.3389\/fcimb.2023.1340135"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1340135","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,15]]},"article-number":"1340135"}}