Efflux pumpes types

AcrAB-TolC efflux pump

 AcrAB-TolC, one of the efflux pumps, primarily expressed in Escherichia coli, consists of the outer membrane protein TolC, the inner membrane transporter AcrB, and the periplasmic adapter protein AcrA (Fanelli et al., 2023).The efflux pump is an intrinsic mechanism of multidrug resistance in Gram-negative bacteria (Zwama, M., & Nishino, K. 2021) AcrA, a highly elongated protein, is thought to bring the outer and inner membranes closer.

It consists of a reactant breaker with monomeric AcrB, which was shown by in vitro reconstitution to be protonated (Compagne et al., 2023). Purified TolC is in a closed state, but TolC is open in the purified AcrAB-TolC complex in the presence of antibiotics or inhibitors. In the absence of ligands, the TolC-locked complex can only be achieved using the disulfide-engineered AcrA-AcrB crosslinking pump . The AcrAB system is primarily expressed in E. coli, and is largely responsible for the property Autoimmune resistance of this organism to dyes, detergents and most lipophilic antibiotics (Roy et al., 2023; Shi et al.,2019).

ACRD Efflux Pumps

AcrD is a component of the efflux pump that mediates the export of aminoglycosides and a few amphipathic compounds such as sodium dodecyl sulfate (SDS), deoxycholate and novobiocin, AcrA is a peripheral fusion protein that also jointly exports aminoglycosides with the cytoplasmic protein AcrD . The biofilm proteins encoded by csgBD, and the efflux pump AcrD have an effect on biofilm formation, and appear to play a special biological function, according to the findings (Guérin et al., 2023; Al-Dahmoshi et al., 2022).The copies showed significant changes supporting this theory. The transcripts of the acrD mutant were compared with that of the acrB mutant, in which a previously released AcrD is not a 'backup' efflux pump, but performs a physiological function in the cell, as evidenced by the fact that the effect was quite distinct ( Buckner et al., 2016).This comparison found 232 major changes in gene expression that were caused only by ACRD inactivation and not by acrB inactivation. Each of the acrB and acrD mutant transcripts contained 169 genes that were differentially expressed compared to the acrB mutant transcript. Experiments have shown that AcrB and AcrD efflux pumps have different substrate profiles when aminoglycoside antibiotics are indicated (Alav et al., 2021; Wójcicki et al., 2021).

EmrAB-TolC efflux pump

 EmrAB components in Escherichia coli were first identified more than decade ago, resistance to hydrophobic toxins such as carbonyl cyanide m chlorophenyl-hydrazone (CCCP) was discovered more than a decade ago (Al Dahmoshi et al., 2022). EmrB is a transmembrane protein with 14 proposed TM domains and homology to MFS vectors, according to preliminary sequence analyses, whereas EmrA has a broad soluble C-terminal domain with a single N-terminal TM domain and homology to MFP, HlyD. EmrAB, together with the outer membrane channel TolC, is thought to form a ternary efflux mechanism dependent on homology with the HlyBD TolC system (Henderson et al., 2021), and these complexes efficiently pump material out of the cell . Other components of TolC-dependent ternary efflux systems are an endomembrane-associated transporter, such as the RND AcrB family transporter or the major superfamily (MFS) transporter EmrB, both catalyzed by H influx, or the ABCuperfamily MacB transporter, which is driven by ATP hydrolysis . a TolC-dependent efflux mechanism is responsible for the export of intracellular metabolites such as enterobactin, porphyrin, and excess cysteine, as well as the expulsion of toxic compounds (Guest, 2017).

MacBA-TolC efflux Pump In Gram-negative bacteria , such as Escherichia.coli, a MacA-MacB TolC pump has been detected (Okada, & Murakami, 2023) .The MacB endomembrane transporter is a non-inclusive member of the ATP-binding cassette (ABC) family (Okada, & Murakami, 2022). and biochemical analyzes revealed that it forms a homodimer. Only the 14- and 15-membered macrolide antibiotics can be transported by MacB (Varela et al., 2021). Under normal laboratory conditions, it was difficult to detect their function in antibiotic resistance. In the AcrAB macrolide-sensitive E. coli strain, only overexpression of MacAB might increase resistance to macrolide antibiotics.

On the other hand, MacAB has been recently linked to the secretion of heat-stable enterotoxin E. s, expected to share structural similarities with AcrA (44%) (Okada, U., & Murakami, S. 2023).The periplasmic near-membrane domain of MacA is required for MacA interactions and this MacB. By modulating MacA transmembrane near-domain formation and disrupting proper assembly of the MacA-MacB complex, a single G353A substitution in this domain impairs MacAB-TolC function (Alav, et al ., 2022).

References
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Alav, I., Bavro, V. N., & Blair, J. M. (2022). A role for the periplasmic adaptor protein AcrA in vetting substrate access to the RND efflux transporter AcrB. Scientific Reports, 12(1), 4752.

Alav, I., Kobylka, J., Kuth, M. S., Pos, K. M., Picard, M., Blair, J. M., & Bavro, V. N. (2021). Structure, assembly, and function of tripartite efflux and type 1 secretion systems in gram-negative bacteria. Chemical Reviews, 121(9), 5479-5596.

Al-Dahmoshi, H., Ali, S. A., & Al-Khafaji, N. (2022). Efflux Pumps among Urinary E. coli and K. pneumoniae Local Isolates in Hilla City, Iraq. The Global Antimicrobial Resistance Epidemic: Innovative Approaches and Cutting-Edge Solutions, 239.

Buckner, M. M., Blair, J. M., La Ragione, R. M., Newcombe, J., Dwyer, D. J., Ivens, A., & Piddock, L. J. (2016). Beyond antimicrobial resistance: evidence for a distinct role of the AcrD efflux pump in Salmonella biology. MBio, 7(6), 10-1128.

Compagne, N., Vieira Da Cruz, A., Müller, R. T., Hartkoorn, R. C., Flipo, M., & Pos, K. M. (2023). Update on the discovery of efflux pump inhibitors against critical priority gram-negative bacteria. Antibiotics, 12(1), 180.

Fanelli, G., Pasqua, M., Prosseda, G., Grossi, M., & Colonna, B. (2023). AcrAB efflux pump impacts on the survival of adherent-invasive Escherichia coli strain LF82 inside macrophages. Scientific Reports, 13(1), 2692.

Guérin, F., Gravey, F., Reissier, S., Penven, M., Michaux, C., Le Hello, S., & Cattoir, V. (2023). Temocillin Resistance in the Enterobacter cloacae Complex Is Conferred by a Single Point Mutation in BaeS, Leading to Overexpression of the AcrD Efflux Pump. Antimicrobial Agents and Chemotherapy, 67(6), e00358-23.

Guest, R. L. (2017). Regulation of respiration by the Cpx response in enteropathogenic Escherichia coli.

Henderson, P. J., Maher, C., Elbourne, L. D., Eijkelkamp, B. A., Paulsen, I. T., & Hassan, K. A. (2021). Physiological functions of bacterial “multidrug” efflux pumps. Chemical reviews, 121(9), 5417-5478.

Okada, U., & Murakami, S. (2022). Structural and functional characteristics of the tripartite ABC transporter. Microbiology, 168(11), 001257.

Okada, U., & Murakami, S. (2023). Structural and Functional Aspects of the Macrolide Efflux Transporter, MacB—A Tripartite ABC Transporter. In Therapeutic Protein Targets for Drug Discovery and Clinical Evaluation: Bio-Crystallography and Drug Design (pp. 1-23).

Roy, S., Hasan, I., & Guo, B. (2023). Recent advances in nanoparticle mediated antibacterial applications. Coordination Chemistry Reviews, 482, 215075.

Shi, X., Chen, M., Yu, Z., Bell, J. M., Wang, H., Forrester, I., ... & Wang, Z. (2019). In situ structure and assembly of the multidrug efflux pump AcrAB-TolC. Nature communications, 10(1), 2635.

Varela, M. F., Stephen, J., Lekshmi, M., Ojha, M., Wenzel, N., Sanford, L. M., ... & Kumar, S. H. (2021). Bacterial resistance to antimicrobial agents. Antibiotics, 10(5), 593.

Wójcicki, M., Świder, O., Daniluk, K. J., Średnicka, P., Akimowicz, M., Roszko, M. Ł., & Juszczuk-Kubiak, E. (2021). Transcriptional regulation of the multiple resistance mechanisms in salmonella—a review. Pathogens, 10(7), 801.

Zwama, M., & Nishino, K. (2021). Ever-adapting RND efflux pumps in Gram-negative multidrug-resistant pathogens: a race against time. Antibiotics, 10(7), 774.

مواضيع ذات صلة

الكامبيلوباكتر Campylobacter والهيلكوباكتر Helicobacter

انواع بكتريا الضمة Vibrio species

السالمونيلا Salmonella

Salmonella Food-borne illness

Genomics and Bacterial Pathogenicity

الايشيريشيا القولونية Escherichia coli

العائلة المعوية Enterobacteriaceae

دورة تضاعف العاثي البكتيري

Bacillus anthracis

Coagulase-Negative Staphylococci

Viridans Streptococci

Efflux Pumps