The highly conserved domain of RND multidrug efflux pumps in pathogenic Gram-negative bacteria

Milad Shahini Shams Abadi; Abolfazl Gholipour; Nahal Hadi

doi:10.14715/cmb/2018.64.13.15

Issue

Vol. 64 No. 13: Issue 13

Issue Published : November 2, 2018

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The highly conserved domain of RND multidrug efflux pumps in pathogenic Gram-negative bacteria

https://doi.org/10.14715/cmb/2018.64.13.15

Milad Shahini Shams Abadi

Department of Bacteriology & Virology, School of medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abolfazl Gholipour

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

Nahal Hadi

Department of Bacteriology & Virology, School of medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Corresponding Author(s) : Nahal Hadi

nahalhadi@gmail.com

Cellular and Molecular Biology, Vol. 64 No. 13: Issue 13
Article Published : October 30, 2018

Abstract

RND (Resistance-Nodulation-Division) family transporters have a vital role in both intrinsic and acquired multi-drug resistance in Gram-negative bacteria. It is important to find a conserved domain in the RND family between different pathogenic bacteria for diagnostic and therapeutic purpose. Total sequences of three-component system RND efflux pumps were retrieved from NCBI nucleotide and protein database and were subjected to conservation and variation analysis using the multiple sequence alignment feature of the CLC workbench. The phylogenetic tree for main transporters was drawn and the three-dimensional structure was also evaluated. From the sequence conservation analysis, highly conserved residues with 282 base pair (94 amino acid) long were identified. The location of the highly conserved domain is positioned in the domain 1 crystallographic structure of AcrB Escherichia coli and MexB Pseudomonas aeruginosa. The main transporter component phylogenetic tree shows the clusters of diï¬€erent genotypes and their evolutionary association. Each of three components of RND proteins is crucial for drug efflux, and the absence of even one component makes the entire complex totally nonfunctional. Therefore, this highly conserved region can be used to disable the RND multidrug efflux pumps. In addition, this highly conserved can also be used for diagnostic aspects.

Keywords

RND multidrug efflux pumps Conserved domain Gram-negative bacteria.

Shahini Shams Abadi, M., Gholipour, A., & Hadi, N. (2018). The highly conserved domain of RND multidrug efflux pumps in pathogenic Gram-negative bacteria. Cellular and Molecular Biology, 64(13), 79–83. https://doi.org/10.14715/cmb/2018.64.13.15

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References

Paulsen IT, Park JH, Choi PS, Saier MH. A family of Gram-negative bacterial outer membrane factors that function in the export of proteins, carbohydrates, drugs and heavy metals from Gram-negative bacteria. In; 1997. p.1-8.
Putman M, van Veen HW, Konings WN. Molecular properties of bacterial multidrug transporters. Microbiology and molecular biology reviews : MMBR 2000; 64: 672-93.
Li X-Z, Plésiat P, Nikaido H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clinical microbiology reviews 2015; 28: 337-418.
Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE. Molecular cloning and characterization of acrA and acrE genes of Escherichia coli. Journal of Bacteriology 1993; 175: 6299-313.
Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE. Genes acrA and acrB encode a stress"induced efflux system of Escherichia coli. Molecular Microbiology 1995; 16: 45-55.
Koronakis V, Eswaran J, Hughes C. Structure and function of TolC: the bacterial exit duct for proteins and drugs. Annual review of biochemistry 2004; 73: 467-89.
Kumar A, Worobec EA. Cloning, sequencing, and characterization of the SdeAB multidrug efflux pump of Serratia marcescens. Antimicrobial Agents and Chemotherapy 2005; 49: 1495-501.
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Mitchell A, Chang HY, Daugherty L, Fraser M, Hunter S, Lopez R, et al. The InterPro protein families database: The classification resource after 15 years. Nucleic Acids Research 2015; 43: D213-D21.
Shahini Shams Abadi M, Siadat SD, Vaziri F, Davari M, Fateh A, Pourazar S, et al. Distribution and diversity of hmw1A among invasive nontypeable Haemophilus influenzae isolates in Iran. Avicenna Journal of Medical Biotechnology 2016; 8.
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Blair JM, Piddock LJ. Structure, function and inhibition of RND efflux pumps in Gram-negative bacteria: an update. In; 2009. p.512-9.
Paulsen IT. Multidrug efflux pumps and resistance: Regulation and evolution. In; 2003. p.446-51.
Pumbwe L, Chang A, Smith RL, Wexler HM. Clinical significance of overexpression of multiple RND-family efflux pumps in Bacteroides fragilis isolates. Journal of antimicrobial chemotherapy 2006; 58: 543-8.
Piddock LJ. Multidrug-resistance efflux pumps? not just for resistance. Nature Reviews Microbiology 2006; 4: 629-36.
Nikaido H, Takatsuka Y. Mechanisms of RND multidrug efflux pumps. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 2009; 1794: 769-81.
Poole K. Efflux pumps as antimicrobial resistance mechanisms. Annals of medicine 2007; 39: 162-76.
Eswaran J, Koronakis E, Higgins MK, Hughes C, Koronakis V. Three's company: component structures bring a closer view of tripartite drug efflux pumps. Current opinion in structural biology 2004; 14: 741-7.
Murakami S, Nakashima R, Yamashita E, Yamaguchi A. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 2002; 419: 587-93.
Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science 2006; 313: 1295-8.
Sennhauser G, Bukowska MA, Briand C, Grütter MG. Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa. Journal of molecular biology 2009; 389: 134-45.

References

Paulsen IT, Park JH, Choi PS, Saier MH. A family of Gram-negative bacterial outer membrane factors that function in the export of proteins, carbohydrates, drugs and heavy metals from Gram-negative bacteria. In; 1997. p.1-8.

Putman M, van Veen HW, Konings WN. Molecular properties of bacterial multidrug transporters. Microbiology and molecular biology reviews : MMBR 2000; 64: 672-93.

Li X-Z, Plésiat P, Nikaido H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clinical microbiology reviews 2015; 28: 337-418.

Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE. Molecular cloning and characterization of acrA and acrE genes of Escherichia coli. Journal of Bacteriology 1993; 175: 6299-313.

Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE. Genes acrA and acrB encode a stress"induced efflux system of Escherichia coli. Molecular Microbiology 1995; 16: 45-55.

Koronakis V, Eswaran J, Hughes C. Structure and function of TolC: the bacterial exit duct for proteins and drugs. Annual review of biochemistry 2004; 73: 467-89.

Kumar A, Worobec EA. Cloning, sequencing, and characterization of the SdeAB multidrug efflux pump of Serratia marcescens. Antimicrobial Agents and Chemotherapy 2005; 49: 1495-501.

Watson JD, Laskowski RA, Thornton JM. Predicting protein function from sequence and structural data. In; 2005. p.275-84.

Mitchell A, Chang HY, Daugherty L, Fraser M, Hunter S, Lopez R, et al. The InterPro protein families database: The classification resource after 15 years. Nucleic Acids Research 2015; 43: D213-D21.

Shahini Shams Abadi M, Siadat SD, Vaziri F, Davari M, Fateh A, Pourazar S, et al. Distribution and diversity of hmw1A among invasive nontypeable Haemophilus influenzae isolates in Iran. Avicenna Journal of Medical Biotechnology 2016; 8.

Pandit SB, Bhadra R, Gowri VS, Balaji S, Anand B, Srinivasan N. SUPFAM: a database of sequence superfamilies of protein domains. BMC bioinformatics 2004; 5: 28-.

Blair JM, Piddock LJ. Structure, function and inhibition of RND efflux pumps in Gram-negative bacteria: an update. In; 2009. p.512-9.

Paulsen IT. Multidrug efflux pumps and resistance: Regulation and evolution. In; 2003. p.446-51.

Pumbwe L, Chang A, Smith RL, Wexler HM. Clinical significance of overexpression of multiple RND-family efflux pumps in Bacteroides fragilis isolates. Journal of antimicrobial chemotherapy 2006; 58: 543-8.

Piddock LJ. Multidrug-resistance efflux pumps? not just for resistance. Nature Reviews Microbiology 2006; 4: 629-36.

Nikaido H, Takatsuka Y. Mechanisms of RND multidrug efflux pumps. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 2009; 1794: 769-81.

Poole K. Efflux pumps as antimicrobial resistance mechanisms. Annals of medicine 2007; 39: 162-76.

Eswaran J, Koronakis E, Higgins MK, Hughes C, Koronakis V. Three's company: component structures bring a closer view of tripartite drug efflux pumps. Current opinion in structural biology 2004; 14: 741-7.

Murakami S, Nakashima R, Yamashita E, Yamaguchi A. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 2002; 419: 587-93.

Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science 2006; 313: 1295-8.

Sennhauser G, Bukowska MA, Briand C, Grütter MG. Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa. Journal of molecular biology 2009; 389: 134-45.

Author biographies is not available.