A novel mechanism of action of ketoconazole: inhibition of the NorA efflux pump system and biofilm formation in multidrug-resistant Staphylococcus aureus

References

• Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268–281. doi:10.1111/j.1469-0691.2011.03570.x21793988
   PubMed Web of Science ®Google Scholar
• Kumar A, Schweizer HP. Bacterial resistance to antibiotics: active efflux and reduced uptake. Adv Drug Deliv Rev. 2005;57(10):1486–1513. doi:10.1016/j.addr.2005.04.00415939505
   PubMed Web of Science ®Google Scholar
• Fernandes A, Dias M. The microbiological profiles of infected prosthetic implants with an emphasis on the organisms which form biofilms. J Clin Diagn Res. 2013;7(2):219–223.23543034
   PubMedGoogle Scholar
• Siala W, Kucharíková S, Braem A, et al. The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase. Nat Commun. 2016;7:13286. doi:10.1038/ncomms1328627808087
   PubMed Web of Science ®Google Scholar
• Van Bambeke F, Glupczynski Y, Plesiat P, Pechere JC, Tulkens PM. Antibiotic efflux pumps in prokaryotic cells: occurrence, impact on resistance and strategies for the future of antimicrobial therapy. J Antimicrob Chemother. 2003;51(5):1055–1065.12697642
   PubMed Web of Science ®Google Scholar
• Kalia NP, Mahajan P, Mehra R, et al. Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus. J Antimicrob Chemother. 2012;67(10):2401–2408. doi:10.1093/jac/dks23222807321
   PubMed Web of Science ®Google Scholar
• Fiamegos YC, Kastritis PL, Exarchou V, et al. Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from artemisia absinthium against gram-positive pathogenic bacteria. PLoS One. 2011;6(4):e18127. doi:10.1371/journal.pone.001812721483731
   PubMed Web of Science ®Google Scholar
• Tintino SR, Oliveira-Tintino CDM, Campina FF, et al. Vitamin K enhances the effect of antibiotics inhibiting the efflux pumps of Staphylococcus aureus strains. Med Chem Res. 2018;27(1):261–267. doi:10.1007/s00044-017-2063-y
   Web of Science ®Google Scholar
• Zgurskaya HI, Nikaido H. Multidrug resistance mechanisms: drug efflux across two membranes. Mol Microbiol. 2000;37(2):219–225. doi:10.1046/j.1365-2958.2000.01926.x10931319
   PubMed Web of Science ®Google Scholar
• Aeschlimann JR, Dresser LD, Kaatz GW, Rybak MJ. Effects of NorA inhibitors on in vitro antibacterial activities and postantibiotic effects of levofloxacin, ciprofloxacin, and norfloxacin in genetically related strains of staphylococcus aureus. Antimicrob Agents Chemother. 1999;43(2):335–340. doi:10.1128/AAC.43.2.3359925528
   PubMed Web of Science ®Google Scholar
• Sud IJ, Feingold DS. Action of antifungal imidazoles on Staphylococcus aureus. Antimicrob Agents Chemother. 1982;22(3):470–474. doi:10.1128/AAC.22.3.4706291453
   PubMed Web of Science ®Google Scholar
• CLSI. Performance standards of antimicrobial disk susceptibility test: ninth Informational Supplement. NCCLS document M100-S9. National Committee for Clinical Laboratory Standards, 2008:120–126; Wayne, PA: Clinical and Laboratory Standards Institute.
   Google Scholar
• Kristiansen JE, Thomsen VF, Martins A, Viveiros M, Amaral L. Non-antibiotics reverse resistance of bacteria to antibiotics. In Vivo. 2010;24(5):751–754.20952744
   PubMed Web of Science ®Google Scholar
• CLSI CaLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard. 8th ed. Broth Microdilution Method Wayne, PA: CLSI; 2009.
   Google Scholar
• Huang L, Sun L, Xu G, Xia T. Differential susceptibility to carbapenems due to the AdeABC efflux pump among nosocomial outbreak isolates of acinetobacter baumannii in a Chinese hospital. Diagn Microbiol Infect Dis. 2008;62(3):326–332. doi:10.1016/j.diagmicrobio.2008.06.00818687557
   PubMed Web of Science ®Google Scholar
• Paixao L, Rodrigues L, Couto I, et al. Fluorometric determination of ethidium bromide efflux kinetics in escherichia coli. J Biol Eng. 2009;3:18. doi:10.1186/1754-1611-3-1819835592
   PubMedGoogle Scholar
• Costa SS, Falcao C, Viveiros M, et al. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus. BMC Microbiol. 2011;11:241. doi:10.1186/1471-2180-11-24122032541
   PubMed Web of Science ®Google Scholar
• Wei GX, Campagna AN, Bobek LA. Effect of MUC7 peptides on the growth of bacteria and on streptococcus mutans biofilm. J Antimicrob Chemother. 2006;57(6):1100–1109. doi:10.1093/jac/dkl12016595638
   PubMed Web of Science ®Google Scholar
• DeMarco CE, Cushing LA, Frempong-Manso E, Seo SM, Jaravaza TA, Kaatz GW. Efflux-related resistance to norfloxacin, dyes, and biocides in bloodstream isolates of Staphylococcus aureus. Antimicrob Agents Chemother. 2007;51(9):3235–3239. doi:10.1128/AAC.00430-0717576828
   PubMed Web of Science ®Google Scholar
• Pages JM, Amaral L. Mechanisms of drug efflux and strategies to combat them: challenging the efflux pump of Gram-negative bacteria. Biochim Biophys Acta. 2009;1794(5):826–833. doi:10.1016/j.bbapap.2008.12.01119150515
   PubMed Web of Science ®Google Scholar
• Saeed A, Bosch A, Bettiol M, Nossa González DL, Erben MF, Lamberti Y. Novel guanidine compound against multidrug-resistant cystic fibrosis-associated bacterial species. Molecules. 2018;23(5):1158. doi:10.3390/molecules23051158
   Web of Science ®Google Scholar
• Tanaka M, Zhang YX, Ishida H, Akasaka T, Sato K, Hayakawa I. Mechanisms of 4-quinolone resistance in quinolone-resistant and methicillin-resistant staphylococcus aureus isolates from Japan and China. J Med Microbiol. 1995;42(3):214–219. doi:10.1099/00222615-42-3-2147884804
   PubMed Web of Science ®Google Scholar
• Ng EY, Trucksis M, Hooper DC. Quinolone resistance mediated by norA: physiologic characterization and relationship to flqB, a quinolone resistance locus on the Staphylococcus aureus chromosome. Antimicrob Agents Chemother. 1994;38(6):1345–1355.8092836
   PubMed Web of Science ®Google Scholar
• Patel D, Kosmidis C, Seo SM, Kaatz GW. Ethidium bromide MIC screening for enhanced efflux pump gene expression or efflux activity in Staphylococcus aureus. Antimicrob Agents Chemother. 2010;54(12):5070–5073. doi:10.1128/AAC.01058-020855743
   PubMed Web of Science ®Google Scholar
• Pages JM, Amaral L, Fanning S. An original deal for new molecule: reversal of efflux pump activity, a rational strategy to combat gram-negative resistant bacteria. Curr Med Chem. 2011;18(19):2969–2980.21651484
   PubMed Web of Science ®Google Scholar
• Takacs D, Cerca P, Martins A, et al. Evaluation of forty new phenothiazine derivatives for activity against intrinsic efflux pump systems of reference escherichia coli, salmonella enteritidis, enterococcus faecalis and staphylococcus aureus strains. In Vivo. 2011;25(5):719–724.21753124
   PubMed Web of Science ®Google Scholar
• Choudhury D, Talukdar AD, Maurya AP, et al. Contribution of efflux pumps in fluroquinolone resistance in multi-drug resistant nosocomial isolates of pseudomanas aeruginosa from a tertiary referral hospital in north east India. Indian J Med Microbiol. 2015;33(1):84–86. doi:10.4103/0255-0857.14838825560007
   PubMed Web of Science ®Google Scholar
• Osei Sekyere J, Amoako DG. Carbonyl Cyanide m-Chlorophenylhydrazine (CCCP) reverses resistance to colistin, but not to carbapenems and tigecycline in multidrug-resistant enterobacteriaceae. Front Microbiol. 2017;8:228. doi:10.3389/fmicb.2017.0022828261184
   PubMed Web of Science ®Google Scholar
• Kaatz GW, Seo SM, Ruble CA. Efflux-mediated fluoroquinolone resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1993;37(5):1086–1094.8517696
   PubMed Web of Science ®Google Scholar
• Huet AA, Raygada JL, Mendiratta K, Seo SM, Kaatz GW. Multidrug efflux pump overexpression in Staphylococcus aureus after single and multiple in vitro exposures to biocides and dyes. Microbiology. 2008;154(Pt 10):3144–3153. doi:10.1099/mic.0.2008/021188-018832320
   PubMed Web of Science ®Google Scholar
• Yoshida H, Bogaki M, Nakamura S, Ubukata K, Konno M. Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. J Bacteriol. 1990;172(12):6942–6949.2174864
   PubMed Web of Science ®Google Scholar
• Truong-Bolduc QC, Dunman PM, Strahilevitz J, Projan SJ, Hooper DC. MgrA is a multiple regulator of two new efflux pumps in staphylococcus aureus. J Bacteriol. 2005;187(7):2395–2405. doi:10.1128/JB.187.7.2395-2405.200515774883
   PubMed Web of Science ®Google Scholar
• Truong-Bolduc QC, Strahilevitz J, Hooper DC. NorC, a new efflux pump regulated by MgrA of staphylococcus aureus. Antimicrob Agents Chemother. 2006;50(3):1104–1107. doi:10.1128/AAC.50.3.1104-1107.200616495280
   PubMed Web of Science ®Google Scholar
• Hassan KA, Skurray RA, Brown MH. Active export proteins mediating drug resistance in staphylococci. J Mol Microbiol Biotechnol. 2007;12(3–4):180–196. doi:10.1159/00009964017587867
   PubMed Web of Science ®Google Scholar
• Rushdy AA, Mabrouk MI, Abu-Sef FA, Kheiralla ZH, Mohamed Abdel-All S, Saleh NM. Contribution of different mechanisms to the resistance to fluoroquinolones in clinical isolates of Salmonella enterica. Braz J Infect Dis. 2013;17(4):431–437. doi:10.1016/j.bjid.2012.11.01223742803
   PubMed Web of Science ®Google Scholar
• Abdi-Ali A, Rahmani-Badi A, Falsafi T, Nikname V. Study of antibiotic resistance by efflux in clinical isolates of Pseudomonas aeruginosa. Pak J Biol Sci. 2007;10(6):924–927.19069890
   PubMedGoogle Scholar
• Singh M, Jadaun GP, Ramdas SK, et al. Effect of efflux pump inhibitors on drug susceptibility of ofloxacin resistant Mycobacterium tuberculosis isolates. Indian J Med Res. 2011;133:535–540.21623040
   PubMed Web of Science ®Google Scholar