Combatting Multidrug Resistance in Bacteria: A Novel Approaches for Assessing Efflux Pumps
Keywords:
Efflux pump Rhodamine 6G (R6G), Multi-drug resistanceAbstract
In order to defend themselves, bacteria contain efflux pumps that assist in evacuating harmful chemicals outside the cell. Antibiotic-active efflux is one of the main mechanisms of drug resistance in bacteria. Membrane transporters use a variety of unrelated compounds as substrates to mediate the efflux process. Because of this, the presence and activity of efflux pumps have a significant impact on the effectiveness of antibiotics, which contributes to bacteria developing drug resistance. Six samples were used in the investigation, and f; foures were found to be E. coli, while the other two were Klebsiella pneumoniae. These isolates demonstrated efflux pump-mediated multidrug resistance. Notably, these bacteria with the Integron integrase 1 gene, called resistant strains, were resistant to 25 different antibiotics. Including Aztreonam, Ampicillin/Sulbactam, Amoxyclav, Cefepime, Cefepime/Tazobactam, Ampicillin, and Cefotaxime, resistance was observed in both E. coli and Klebsiella pneumoniae. Given the complexity of drug efflux transporters, novel approaches are essential to combat multidrug resistance in bacteria effectively. A glucose-triggered rhodamine 6G (R6G) efflux assay from Sigma-Aldrich, USA, was used to test how well efflux pumps work.
References
E. M. Darby et al., “Molecular mechanisms of antibiotic resistance revisited,” Nat Rev Microbiol, vol. 21, no. 5, pp. 280–295, 2023, doi: 10.1038/s41579-022-00820-y.
L. J. V. Piddock, “Multidrug-resistance efflux pumps - Not just for resistance,” Nat Rev Microbiol, vol. 4, no. 8, pp. 629–636, 2006, doi: 10.1038/nrmicro1464.
X. Z. Li and H. Nikaido, “Efflux-Mediated Drug Resistance in Bacteria,” Drugs, vol. 64, no. 2, pp. 159–204, 2004, doi: 10.2165/00003495-200464020-00004.
M. N. Alekshun and S. B. Levy, “Molecular Mechanisms of Antibacterial Multidrug Resistance,” Cell, vol. 128, no. 6, pp. 1037–1050, 2007, doi: 10.1016/j.cell.2007.03.004.
M. A. Webber and L. J. V. Piddock, “The importance of efflux pumps in bacterial antibiotic resistance,” Journal of Antimicrobial Chemotherapy, vol. 51, no. 1, pp. 9–11, 2003, doi: 10.1093/jac/dkg050.
K. Poole, “Efflux-mediated resistance to fluoroquinolones in gram-negative bacteria,” Antimicrob Agents Chemother, vol. 44, no. 9, pp. 2233–2241, 2000, doi: 10.1128/AAC.44.9.2233-2241.2000.
S. Hernando-Amado et al., “Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials,” Drug Resistance Updates, vol. 28, pp. 13–27, 2016, doi: 10.1016/j.drup.2016.06.007.
L. Huang et al., “Bacterial Multidrug Efflux Pumps at the Frontline of Antimicrobial Resistance: An Overview,” Antibiotics, vol. 11, no. 4, p. 520, 2022, doi: 10.3390/antibiotics11040520.
J. B. Buil et al., “Single-center evaluation of an agar-based screening for azole resistance in Aspergillus fumigatus by using VIPcheck,” Antimicrob Agents Chemother, vol. 61, no. 12, pp. 10–1128, 2017, doi: 10.1128/AAC.01250-17.
M. Alcalde-Rico, S. Hernando-Amado, P. Blanco, and J. L. Mart�nez, “Multidrug efflux pumps at the crossroad between antibiotic resistance and bacterial virulence,” Front Microbiol, vol. 7, no. SEP, p. 1483, 2016, doi: 10.3389/fmicb.2016.01483.
J. D. D. Pitout, P. Nordmann, and L. Poirel, “Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance,” Antimicrob Agents Chemother, vol. 59, no. 10, pp. 5873–5884, 2015, doi: 10.1128/AAC.01019-15.
A. Gaurav, P. Bakht, M. Saini, S. Pandey, and R. Pathania, “Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors,” Microbiology (United Kingdom), vol. 169, no. 5, p. 1333, 2023, doi: 10.1099/mic.0.001333.
A. Sharma, V. K. Gupta, and R. Pathania, “Efflux pump inhibitors for bacterial pathogens: From bench to bedside,” Indian Journal of Medical Research, vol. 149, no. 2, pp. 129–145, 2019, doi: 10.4103/ijmr.IJMR_2079_17.
A. Saha, M. Haque, S. Karmaker, and M. Mohanta, “Antibacterial Effects of Some Antiseptics and Disinfectants,” Journal of Life and Earth Science, vol. 3, no. 4, pp. 19–21, 1970, doi: 10.3329/jles.v3i0.7440.
Y. Gbelska, N. Toth Hervay, V. Dzugasova, and A. Konecna, “Measurement of Energy-dependent Rhodamine 6G Efflux in Yeast Species,” Bio Protoc, vol. 7, no. 15, pp. e2428–e2428, 2017, doi: 10.21769/bioprotoc.2428.
A. P. Magiorakos et al., “Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance,” Clinical Microbiology and Infection, vol. 18, no. 3, pp. 268–281, 2012, doi: 10.1111/j.1469-0691.2011.03570.x.
G. Cambray, A.-M. Guerout, and D. Mazel, “Integrons,” Annu Rev Genet, vol. 44, pp. 141–166, 2010.
M. Gillings et al., “The evolution of class 1 integrons and the rise of antibiotic resistance,” J Bacteriol, vol. 190, no. 14, pp. 5095–5100, 2008, doi: 10.1128/JB.00152-08.
P. D. Tamma, Y. Doi, R. A. Bonomo, J. K. Johnson, and P. J. Simner, “A Primer on AmpC ?-Lactamases: Necessary Knowledge for an Increasingly Multidrug-resistant World,” Clinical Infectious Diseases, vol. 69, no. 8, pp. 1446–1455, 2019, doi: 10.1093/cid/ciz173.
J. Sun, Z. Deng, and A. Yan, “Bacterial multidrug efflux pumps: Mechanisms, physiology and pharmacological exploitations,” Biochem Biophys Res Commun, vol. 453, no. 2, pp. 254–267, 2014, doi: 10.1016/j.bbrc.2014.05.090.
H. Nikaido, “Multidrug resistance in bacteria,” Annu Rev Biochem, vol. 78, pp. 119–146, 2009, doi: 10.1146/annurev.biochem.78.082907.145923.
X. Z. Li and H. Nikaido, “Efflux-mediated drug resistance in bacteria: An update,” Drugs, vol. 69, no. 12, pp. 1555–1623, 2009, doi: 10.2165/11317030-000000000-00000.
K. Poole, “Efflux-mediated antimicrobial resistance,” Journal of Antimicrobial Chemotherapy, vol. 56, no. 1, pp. 20–51, 2005.
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