| Structural highlights
Function
[MEXA_PSEAE] The periplasmic linker component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the pump increases antibiotic and solvent efflux capacities. Required for assembly of the MexA/MexB/OprM complex. Implicated in the secretion of the siderophore pyoverdine.[1] [2] [3] The ability to export antibiotics and solvents is dramatically decreased in the presence of the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner membrane is required for efflux. It is thought that the MexB subunit is a proton antiporter.[4] [5] [6] [MEXB_PSEAE] The inner membrane transporter component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the pump increases antibiotic and solvent efflux capacities. Implicated in the secretion of the siderophore pyoverdine.[7] [8] [9] The ability to export antibiotics and solvents is dramatically decreased in the presence of the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner membrane is required for efflux. It is thought that the MexB subunit is a proton antiporter.[10] [11] [12] [OPRM_PSEAE] The outer membrane component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the pump increases antibiotic and solvent efflux capacities. Can replace the OprJ outer membrane component of the MexCD-OprJ pump; the antibiotics exported are those exported by the intact MexCD pump, showing that efflux substrate specificity is not conferred by this component. Serves as the outer membrane component for the MexXY efflux system. Implicated in the secretion of the siderophore pyoverdine. OprM is probably involved in the efflux of the siderophore across the outer membrane.[13] [14] [15] [16] [17] The ability to export antibiotics and solvents is dramatically decreased in the presence of the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner membrane is required for efflux. It is thought that the MexB subunit is a proton antiporter.[18] [19] [20] [21] [22]
Publication Abstract from PubMed
In Pseudomonas aeruginosa, MexAB-OprM plays a central role in multidrug resistance by ejecting various drug compounds, which is one of the causes of serious nosocomial infections. Although the structures of the components of MexAB-OprM have been solved individually by X-ray crystallography, no structural information for fully assembled pumps from P. aeruginosa were previously available. In this study, we present the structure of wild-type MexAB-OprM in the presence or absence of drugs at near-atomic resolution. The structure reveals that OprM does not interact with MexB directly, and that it opens its periplasmic gate by forming a complex. Furthermore, we confirm the residues essential for complex formation and observed a movement of the drug entrance gate. Based on these results, we propose mechanisms for complex formation and drug efflux.
Structures of the wild-type MexAB-OprM tripartite pump reveal its complex formation and drug efflux mechanism.,Tsutsumi K, Yonehara R, Ishizaka-Ikeda E, Miyazaki N, Maeda S, Iwasaki K, Nakagawa A, Yamashita E Nat Commun. 2019 Apr 3;10(1):1520. doi: 10.1038/s41467-019-09463-9. PMID:30944318[23]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
- ↑ Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
- ↑ Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
- ↑ Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
- ↑ Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
- ↑ Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
- ↑ Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
- ↑ Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
- ↑ Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
- ↑ Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
- ↑ Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
- ↑ Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
- ↑ Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
- ↑ Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
- ↑ Srikumar R, Li XZ, Poole K. Inner membrane efflux components are responsible for beta-lactam specificity of multidrug efflux pumps in Pseudomonas aeruginosa. J Bacteriol. 1997 Dec;179(24):7875-81. PMID:9401051
- ↑ Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
- ↑ Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2000 Sep;44(9):2242-6. PMID:10952562
- ↑ Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
- ↑ Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
- ↑ Srikumar R, Li XZ, Poole K. Inner membrane efflux components are responsible for beta-lactam specificity of multidrug efflux pumps in Pseudomonas aeruginosa. J Bacteriol. 1997 Dec;179(24):7875-81. PMID:9401051
- ↑ Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
- ↑ Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2000 Sep;44(9):2242-6. PMID:10952562
- ↑ Tsutsumi K, Yonehara R, Ishizaka-Ikeda E, Miyazaki N, Maeda S, Iwasaki K, Nakagawa A, Yamashita E. Structures of the wild-type MexAB-OprM tripartite pump reveal its complex formation and drug efflux mechanism. Nat Commun. 2019 Apr 3;10(1):1520. doi: 10.1038/s41467-019-09463-9. PMID:30944318 doi:http://dx.doi.org/10.1038/s41467-019-09463-9
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