Permeabiliteye Bağlı Direnç (OMP ve Atım Pompaları)
Özet
Bakteriler, çevresel koşullara karşı hızlı uyum sağlayabilen mikroorganizmalardır. Hayatta kalma stratejileri arasında zar geçirgenliğinin düzenlemesi ve birçok molekülün taşınmasında rol oynayan aktif atım pompaları önemli bir yer tutar. Hücre zarı, bakterilerin yaşamsal işlevlerini sürdürebilmesi için seçici bir bariyer görevi görür ve dış ortamdan gelen maddelerin girişini kontrol eder. Özellikle gram negatif bakterilerde, dış membranda bulunan porin adı verilen protein kanalları, antibiyotik gibi moleküllerin hücre içine alınmasını sınırlandırarak antibiyotiklere direnç gelişimine katkıda bulunur. ß-laktamlar, hücre duvarı sentezini inhibe ederek bakterisidal etki gösteren ve sıklıkla tercih edilen antibiyotiklerden biridir. Her ne kadar β-laktam dirence neden olan ana mekanizma bir β-laktamaz üretimi olsa da porin kaybı veya mutasyonları, dirençte önemli rol oynar. Bunun yanı sıra, aktif atım pompaları bakteriler için kritik bir savunma mekanizmasıdır. Bu taşıyıcı sistemler, hücre içine giren toksik maddeleri, metabolik atıkları ve antibiyotikleri aktif olarak dışarı atarak bakterinin zarar görmesini engeller. Özellikle gram negatif bakterilerde β-laktam direncinde rol oynayan birçok aktif atım pompası tanımlanmıştır. Bu pompalar, penisilinler, sefalosporinler ve karbapenemler gibi β-laktam antibiyotikleri dışarı atarak hücre içinde etkili konsantrasyonlara ulaşmalarını engeller. Bu mekanizmalar aracılığıyla gelişen β-laktam direnci ciddi enfeksiyonların tedavisini güçleştirmektedir. Günümüzde bu direnç mekanizmalarının daha iyi aydınlatılması yeni tedavi stratejilerinin geliştirilmesi ve eldeki antibiyotiklerin etkinliklerinin arttırılması açısından oldukça önemlidir.
Bacteria are microorganisms that can quickly adopt to environmental conditions. Among survival strategies, regulation of membrane permeability and active efflux pumps that transport many molecules play an essential role. The cell membrane acts as a selective barrier to enable bacteria to maintain their vital functions and controls the entry of substances from the external environment. In gram negative bacteria, protein channels called porins located in the outer membrane contribute to the development of antibiotic resistance by limiting the entry of molecules such as antibiotics into the cell. ß-lactams are one of the most preferred antibiotics that exhibit bactericidal effects by inhibiting cell wall synthesis. Although the primary mechanism of resistance to β-lactams is the production of β-lactamases, loss or mutations of porins play an essential role in resistance. Additionally, active efflux pumps are a critical defense mechanism for bacteria. These transport systems actively throw out toxic substances, metabolic waste, and antibiotics from the cell, preventing harm to the bacterium. Many active efflux pumps involved in β-lactam resistance have been identified in gram negative bacteria. These pumps prevent β-lactam antibiotics, such as penicillin, cephalosporins, and carbapenems, from reaching effective concentrations within the cell by expelling them. β-lactam resistance developed through these mechanisms complicates the treatment of serious infections. Today, a better understanding of these resistance mechanisms is crucial for developing new treatment strategies and enhancing the effectiveness of existing antibiotics.
Referanslar
Uddin TM, Chakraborty AJ, Khusro A, et al. Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects. J Infect Public Health. 2021;14(12):1750-1766.
Christaki E, Marcou M, Tofarides A. Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence. J Mol Evol. 2020;88(1):26-40.
Rice LB. Mechanisms of resistance and clinical relevance of resistance to β-lactams, glycopeptides, and fluoroquinolones. Mayo Clin Proc. 2012;87(2):198-208.
Ghai I, Ghai S. Understanding antibiotic resistance via outer membrane permeability. Infect Drug Resist. 2018;11:523-530.
Belay WY, Getachew M, Tegegne BA, et al. Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: a review. Front Pharmacol. 2024;5:1444781.
Zhang F, Cheng W. The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies. Antibiotics. 2022;11(9):1215.
Maher C, Hassan KA. The Gram-negative permeability barrier: tipping the balance of the in and the out. MBio. 2023;14(6): e0120523.
Munita JM, Arias CA. Mechanisms of Antibiotic Resistance. Microbiol Spectr. 2016;4(2): 10.1128/microbiolspec.VMBF-0016-2015.
Zgurskaya HI, Rybenkov VV. Permeability barriers of Gram-negative pathogens. Ann N Y Acad Sci. 2020;1459(1):5-18.
Impey RE, Hawkins DA, Sutton JM, Soares da Costa TP. Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria. Antibiotics (Basel). 2020;19;9(9):623.
Pagès JM, James CE, Winterhalter M. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol. 2008; 6(12):893-903.
Hasdemir U. The role of cell wall organization and active efflux pump systems in multidrug resistance of bacteria. Mikrobiyol Bul. 2007;41(2):309-27.
Liu YF, Yan JJ, Ko WC, Tsai SH, Wu JJ. Characterization of carbapenem-non-susceptible Escherichia coli isolates from a university hospital in Taiwan. J Antimicrob Chemother. 2008;61(5):1020-3.
Gauba A, Rahman KM. Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria. Antibiotics. 2023;12(11):1590.
Zhou G, Wang Q, Wang Y, et al. Outer Membrane Porins Contribute to Antimicrobial Resistance in Gram-Negative Bacteria. Microorganisms. 2023; 11(7):1690.
Lou H, Chen M, Black SS, et al. Altered antibiotic transport in OmpC mutants isolated from a series of clinical strains of multi-drug resistant E. coli. PLoS One 2011; 6:e25825.
Low AS, MacKenzie FM, Gould IM, Booth IR. Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long-term antibiotic therapy. Mol Microbiol 2001;42:619–630.
Simonet V, Malléa M, Pagès JM. Substitutions in the eyelet region disrupt cefepime diffusion through the Escherichia coli OmpF channel. Antimicrob Agents Chemother 2000;44:311–315.
Park S, Kim H, Ko KS. Reduced virulence in tigecycline-resistant Klebsiella pneumoniae caused by overexpression of ompR and down-regulation of ompK35. J Biomed Sci. 2023;30(1):22.
Knopp M, Andersson DI. Amelioration of the fitness costs of antibiotic resistance due to reduced outer membrane permeability by upregulation of alternative porins. Mol Biol Evol. 2015;32:3252–3263.
Rocker A, Lacey JA, Belousoff MJ, et al. Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae. mBio. 2020;11(2):e00603-20.
David S, Wong JLC, Sanchez-Garrido J, et al. Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae. PLoS Pathog. 2022;18(7):e1010334.
Thiolas A, Bornet C, Davin-Régli A, Pagès J-M, Bollet C. Resistance to imipenem, cefepime, and cefpirome associated with mutation in Omp36 osmoporin of Enterobacter aerogenes. Biochem Biophys Res Commun 2004;317:851–856.
Dé E, Baslé A, Jaquinod M, et al. A new mechanism of antibiotic resistance in Enterobacteriaceae induced by a structural modification of the major porin. Mol Microbiol 2001;41:189–198.
Glen KA, Lamont IL. β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects. Pathogens. 2021;10(12):1638.
Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Bio Rev 2003;67: 593-656.
Zgurskaya HI, Löpez CA, Gnanakaran S. Permeability Barrier of Gram-Negative Cell Envelopes and Approaches To Bypass It. ACS Infect Dis. 2015;1(11):512-522.
Uppalapati SR, Sett A, Pathania R. The Outer Membrane Proteins OmpA, CarO, and OprD of Acinetobacter baumannii Confer a Two-Pronged Defense in Facilitating Its Success as a Potent Human Pathogen. Front Microbiol. 2020;11:589234
Sugawara E, Nikaido H. OmpA is the principal nonspecific slow porin of Acinetobacter baumannii. J Bacteriol. 2012;194(15):4089-96.
Sharma A, Gupta VK, Pathania R. Efflux pump inhibitors for bacterial pathogens: From bench to bedside. Indian J Med Res. 2019;149(2):129-145.
Gaurav A, Bakht P, Saini M, Pandey S, Pathania R. Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors. Microbiology (Reading). 2023;169(5):001333.
Poole K. Efflux pumps as antimicrobial resistance mechanisms. Ann Med. 2007;39(3):162-6.
Zack KM, Sorenson T, Joshi SG. Types and Mechanisms of Efflux Pump Systems and the Potential of Efflux Pump Inhibitors in the Restoration of Antimicrobial Susceptibility, with a Special Reference to Acinetobacter baumannii. Pathogens. 2024;13(3):197.
Kumawat M, Nabi B, Daswani M, et al. Role of bacterial efflux pump proteins in antibiotic resistance across microbial species. Microb Pathog. 2023;181:106182.
Nikaido H, Pagès JM. Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol Rev. 2012;36(2):340-63.
Jang S. AcrAB-TolC, a major efflux pump in Gram negative bacteria: toward understanding its operation mechanism. BMB Rep. 2023;56(6):326-334.
Adler M, Anjum M, Andersson DI, Sandegren L. Combinations of mutations in envZ, ftsI, mrdA, acrB and acrR can cause high-level carbapenem resistance in Escherichia coli. J Antimicrob Chemother. 2016;71(5):1188-1198.
Chetri S, Singha M, Bhowmik D, et al. Transcriptional response of OmpC and OmpF in Escherichia coli against differential gradient of carbapenem stress. BMC Res Notes. 2019;12(1):138.
Sekar P, Mamtora D, Bhalekar P, Krishnan P. AcrAB-TolC Efflux Pump Mediated Resistance to Carbapenems among Clinical Isolates of Enterobacteriaceae. J Pure Appl Microbiol. 2022;16(3):1982-1989.
Hussein RA, Al-Kubaisy SH, Al-Ouqaili MTS. The influence of efflux pump, outer membrane permeability and β-lactamase production on the resistance profile of multi, extensively and pandrug resistant Klebsiella pneumoniae. J Infect Public Health. 2024;17(11):102544.
Muhsin EA, Sajid Al-Jubori S, Abdulhemid Said L. Prevalence of Efflux Pumpand Porin-Related Antimicrobial Resistance in Clinical Klebsiella pneumoniae in Baghdad, Iraq. Arch Razi Inst. 2022;77(2):785-798.
Li J, Xu Q, Ogurek S, et al. Efflux Pump AcrAB Confers Decreased Susceptibility to Piperacillin-Tazobactam and Ceftolozane-Tazobactam in Tigecycline-Non-Susceptible Klebsiella pneumoniae. Infect Drug Resist. 2020;13:4309-4319.
Kaczmarek FS, Gootz TD, Dib-Hajj F, et al. Genetic and molecular characterization of β-lactamase-negative ampicillin-resistant Haemophilus influenzae with unusually high resistance to ampicillin. Antimicrob Agents Chemother. 2004;48(5):1630-9.
Kobayashi N, Tamura N, van Veen HW, Yamaguchi A, Murakami S. β-Lactam selectivity of multidrug transporters AcrB and AcrD resides in the proximal binding pocket. J Biol Chem. 2014;289(15):10680-10690.
De Gaetano GV, Lentini G, Famà A, Coppolino F, Beninati C. Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps. Antibiotics (Basel). 2023;12(6):965.
Cabot G, Ocampo-Sosa AA, Tubau F, et al. Overexpression of AmpC and efflux pumps in Pseudomonas aeruginosa isolates from bloodstream infections: prevalence and impact on resistance in a Spanish multicenter study. Antimicrob Agents Chemother. 2011;55(5):1906-11.
Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally enco¬ded resistance mechanisms, Clin Microbiol Rev 2009;22(4):582-610.
Xavier DE, Picao RC, Girardello R, Fehlberg LC, Gales AC. Efflux pumps expression and its associ¬ation with porin down-regulation and β-lactamase production among Pseudomonas aeruginosa cau¬sing bloodstream infections in Brazil, BMC Microbiology 2010;10:217.
Dulanto Chiang A, Patil PP, Beka L, et al. Hypermutator strains of Pseudomonas aeruginosa reveal novel pathways of resistance to combinations of cephalosporin antibiotics and β-lactamase inhibitors. PLoS Biol. 2022;20(11):e3001878.
Nichols WW, Lahiri SD, Bradford PA, Stone GG. The primary pharmacology of ceftazidime/avibactam: resistance in vitro. J Antimicrob Chemother. 2023;78(3):569-585.
Davin-Regli A, Pages J-M, Ferrand A. Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria. Antibiotics. 2021;10(9):1117.
Zack KM, Sorenson T, Joshi SG. Types and Mechanisms of Efflux Pump Systems and the Potential of Efflux Pump Inhibitors in the Restoration of Antimicrobial Susceptibility, with a Special Reference to Acinetobacter baumannii. Pathogens. 2024;13(3):197.
Abdi SN, Ghotaslou R, Ganbarov K, et al. Acinetobacter baumannii Efflux Pumps and Antibiotic Resistance. Infect Drug Resist. 2020;13:423-434.
Gautam V, Kumar S, Patil PP, et al.Exploring the Interplay of Resistance Nodulation Division Efflux Pumps, AmpC and OprD in Antimicrobial Resistance of Burkholderia cepacia Complex in Clinical Isolates. Microb Drug Resist. 2020; 26(10):1144-1152.
Referanslar
Uddin TM, Chakraborty AJ, Khusro A, et al. Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects. J Infect Public Health. 2021;14(12):1750-1766.
Christaki E, Marcou M, Tofarides A. Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence. J Mol Evol. 2020;88(1):26-40.
Rice LB. Mechanisms of resistance and clinical relevance of resistance to β-lactams, glycopeptides, and fluoroquinolones. Mayo Clin Proc. 2012;87(2):198-208.
Ghai I, Ghai S. Understanding antibiotic resistance via outer membrane permeability. Infect Drug Resist. 2018;11:523-530.
Belay WY, Getachew M, Tegegne BA, et al. Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: a review. Front Pharmacol. 2024;5:1444781.
Zhang F, Cheng W. The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies. Antibiotics. 2022;11(9):1215.
Maher C, Hassan KA. The Gram-negative permeability barrier: tipping the balance of the in and the out. MBio. 2023;14(6): e0120523.
Munita JM, Arias CA. Mechanisms of Antibiotic Resistance. Microbiol Spectr. 2016;4(2): 10.1128/microbiolspec.VMBF-0016-2015.
Zgurskaya HI, Rybenkov VV. Permeability barriers of Gram-negative pathogens. Ann N Y Acad Sci. 2020;1459(1):5-18.
Impey RE, Hawkins DA, Sutton JM, Soares da Costa TP. Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria. Antibiotics (Basel). 2020;19;9(9):623.
Pagès JM, James CE, Winterhalter M. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol. 2008; 6(12):893-903.
Hasdemir U. The role of cell wall organization and active efflux pump systems in multidrug resistance of bacteria. Mikrobiyol Bul. 2007;41(2):309-27.
Liu YF, Yan JJ, Ko WC, Tsai SH, Wu JJ. Characterization of carbapenem-non-susceptible Escherichia coli isolates from a university hospital in Taiwan. J Antimicrob Chemother. 2008;61(5):1020-3.
Gauba A, Rahman KM. Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria. Antibiotics. 2023;12(11):1590.
Zhou G, Wang Q, Wang Y, et al. Outer Membrane Porins Contribute to Antimicrobial Resistance in Gram-Negative Bacteria. Microorganisms. 2023; 11(7):1690.
Lou H, Chen M, Black SS, et al. Altered antibiotic transport in OmpC mutants isolated from a series of clinical strains of multi-drug resistant E. coli. PLoS One 2011; 6:e25825.
Low AS, MacKenzie FM, Gould IM, Booth IR. Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long-term antibiotic therapy. Mol Microbiol 2001;42:619–630.
Simonet V, Malléa M, Pagès JM. Substitutions in the eyelet region disrupt cefepime diffusion through the Escherichia coli OmpF channel. Antimicrob Agents Chemother 2000;44:311–315.
Park S, Kim H, Ko KS. Reduced virulence in tigecycline-resistant Klebsiella pneumoniae caused by overexpression of ompR and down-regulation of ompK35. J Biomed Sci. 2023;30(1):22.
Knopp M, Andersson DI. Amelioration of the fitness costs of antibiotic resistance due to reduced outer membrane permeability by upregulation of alternative porins. Mol Biol Evol. 2015;32:3252–3263.
Rocker A, Lacey JA, Belousoff MJ, et al. Global Trends in Proteome Remodeling of the Outer Membrane Modulate Antimicrobial Permeability in Klebsiella pneumoniae. mBio. 2020;11(2):e00603-20.
David S, Wong JLC, Sanchez-Garrido J, et al. Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae. PLoS Pathog. 2022;18(7):e1010334.
Thiolas A, Bornet C, Davin-Régli A, Pagès J-M, Bollet C. Resistance to imipenem, cefepime, and cefpirome associated with mutation in Omp36 osmoporin of Enterobacter aerogenes. Biochem Biophys Res Commun 2004;317:851–856.
Dé E, Baslé A, Jaquinod M, et al. A new mechanism of antibiotic resistance in Enterobacteriaceae induced by a structural modification of the major porin. Mol Microbiol 2001;41:189–198.
Glen KA, Lamont IL. β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects. Pathogens. 2021;10(12):1638.
Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Bio Rev 2003;67: 593-656.
Zgurskaya HI, Löpez CA, Gnanakaran S. Permeability Barrier of Gram-Negative Cell Envelopes and Approaches To Bypass It. ACS Infect Dis. 2015;1(11):512-522.
Uppalapati SR, Sett A, Pathania R. The Outer Membrane Proteins OmpA, CarO, and OprD of Acinetobacter baumannii Confer a Two-Pronged Defense in Facilitating Its Success as a Potent Human Pathogen. Front Microbiol. 2020;11:589234
Sugawara E, Nikaido H. OmpA is the principal nonspecific slow porin of Acinetobacter baumannii. J Bacteriol. 2012;194(15):4089-96.
Sharma A, Gupta VK, Pathania R. Efflux pump inhibitors for bacterial pathogens: From bench to bedside. Indian J Med Res. 2019;149(2):129-145.
Gaurav A, Bakht P, Saini M, Pandey S, Pathania R. Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors. Microbiology (Reading). 2023;169(5):001333.
Poole K. Efflux pumps as antimicrobial resistance mechanisms. Ann Med. 2007;39(3):162-6.
Zack KM, Sorenson T, Joshi SG. Types and Mechanisms of Efflux Pump Systems and the Potential of Efflux Pump Inhibitors in the Restoration of Antimicrobial Susceptibility, with a Special Reference to Acinetobacter baumannii. Pathogens. 2024;13(3):197.
Kumawat M, Nabi B, Daswani M, et al. Role of bacterial efflux pump proteins in antibiotic resistance across microbial species. Microb Pathog. 2023;181:106182.
Nikaido H, Pagès JM. Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol Rev. 2012;36(2):340-63.
Jang S. AcrAB-TolC, a major efflux pump in Gram negative bacteria: toward understanding its operation mechanism. BMB Rep. 2023;56(6):326-334.
Adler M, Anjum M, Andersson DI, Sandegren L. Combinations of mutations in envZ, ftsI, mrdA, acrB and acrR can cause high-level carbapenem resistance in Escherichia coli. J Antimicrob Chemother. 2016;71(5):1188-1198.
Chetri S, Singha M, Bhowmik D, et al. Transcriptional response of OmpC and OmpF in Escherichia coli against differential gradient of carbapenem stress. BMC Res Notes. 2019;12(1):138.
Sekar P, Mamtora D, Bhalekar P, Krishnan P. AcrAB-TolC Efflux Pump Mediated Resistance to Carbapenems among Clinical Isolates of Enterobacteriaceae. J Pure Appl Microbiol. 2022;16(3):1982-1989.
Hussein RA, Al-Kubaisy SH, Al-Ouqaili MTS. The influence of efflux pump, outer membrane permeability and β-lactamase production on the resistance profile of multi, extensively and pandrug resistant Klebsiella pneumoniae. J Infect Public Health. 2024;17(11):102544.
Muhsin EA, Sajid Al-Jubori S, Abdulhemid Said L. Prevalence of Efflux Pumpand Porin-Related Antimicrobial Resistance in Clinical Klebsiella pneumoniae in Baghdad, Iraq. Arch Razi Inst. 2022;77(2):785-798.
Li J, Xu Q, Ogurek S, et al. Efflux Pump AcrAB Confers Decreased Susceptibility to Piperacillin-Tazobactam and Ceftolozane-Tazobactam in Tigecycline-Non-Susceptible Klebsiella pneumoniae. Infect Drug Resist. 2020;13:4309-4319.
Kaczmarek FS, Gootz TD, Dib-Hajj F, et al. Genetic and molecular characterization of β-lactamase-negative ampicillin-resistant Haemophilus influenzae with unusually high resistance to ampicillin. Antimicrob Agents Chemother. 2004;48(5):1630-9.
Kobayashi N, Tamura N, van Veen HW, Yamaguchi A, Murakami S. β-Lactam selectivity of multidrug transporters AcrB and AcrD resides in the proximal binding pocket. J Biol Chem. 2014;289(15):10680-10690.
De Gaetano GV, Lentini G, Famà A, Coppolino F, Beninati C. Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps. Antibiotics (Basel). 2023;12(6):965.
Cabot G, Ocampo-Sosa AA, Tubau F, et al. Overexpression of AmpC and efflux pumps in Pseudomonas aeruginosa isolates from bloodstream infections: prevalence and impact on resistance in a Spanish multicenter study. Antimicrob Agents Chemother. 2011;55(5):1906-11.
Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally enco¬ded resistance mechanisms, Clin Microbiol Rev 2009;22(4):582-610.
Xavier DE, Picao RC, Girardello R, Fehlberg LC, Gales AC. Efflux pumps expression and its associ¬ation with porin down-regulation and β-lactamase production among Pseudomonas aeruginosa cau¬sing bloodstream infections in Brazil, BMC Microbiology 2010;10:217.
Dulanto Chiang A, Patil PP, Beka L, et al. Hypermutator strains of Pseudomonas aeruginosa reveal novel pathways of resistance to combinations of cephalosporin antibiotics and β-lactamase inhibitors. PLoS Biol. 2022;20(11):e3001878.
Nichols WW, Lahiri SD, Bradford PA, Stone GG. The primary pharmacology of ceftazidime/avibactam: resistance in vitro. J Antimicrob Chemother. 2023;78(3):569-585.
Davin-Regli A, Pages J-M, Ferrand A. Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria. Antibiotics. 2021;10(9):1117.
Zack KM, Sorenson T, Joshi SG. Types and Mechanisms of Efflux Pump Systems and the Potential of Efflux Pump Inhibitors in the Restoration of Antimicrobial Susceptibility, with a Special Reference to Acinetobacter baumannii. Pathogens. 2024;13(3):197.
Abdi SN, Ghotaslou R, Ganbarov K, et al. Acinetobacter baumannii Efflux Pumps and Antibiotic Resistance. Infect Drug Resist. 2020;13:423-434.
Gautam V, Kumar S, Patil PP, et al.Exploring the Interplay of Resistance Nodulation Division Efflux Pumps, AmpC and OprD in Antimicrobial Resistance of Burkholderia cepacia Complex in Clinical Isolates. Microb Drug Resist. 2020; 26(10):1144-1152.
