Abstract
Active efflux of antimicrobial agents is one of the most important strategies used by bacteria to defend against antimicrobial factors present in their environment. Mediating many cases of antibiotic resistance are transmembrane efflux pumps, composed of one or more proteins. The Neisseria gonorrhoeae MtrCDE tripartite multidrug efflux pump, belonging to the hydrophobic and amphiphilic efflux resistance-nodulation-cell division (HAE-RND) family, spans both the inner and outer membranes of N. gonorrhoeae and confers resistance to a variety of antibiotics and toxic compounds. We here describe the crystal structure of N. gonorrhoeae MtrE, the outer membrane component of the MtrCDE tripartite multidrug efflux system. This trimeric MtrE channel forms a vertical tunnel extending down contiguously from the outer membrane surface to the periplasmic end, indicating that our structure of MtrE depicts an open conformational state of this channel.
Highlights
Neisseria gonorrhoeae is a Gram-negative diplococcus, which is found only in humans and causes the sexually transmitted disease gonorrhea
One major mechanism that this bacterium uses to repel antimicrobial agents is the expression of multidrug efflux pumps that recognize and actively export a variety of structurally unrelated toxic compounds from the bacterial cell, including antibacterial peptides, long-chain fatty acids, and several clinically important antibiotics [2,3,4,5]
The best characterized and most clinically important efflux system in N. gonorrhoeae is the MtrCDE tripartite multidrug efflux system [6,7,8], which belongs to the hydrophobic and amphiphilic efflux resistance-nodulation-cell division (HAE-RND) family
Summary
Neisseria gonorrhoeae is a Gram-negative diplococcus, which is found only in humans and causes the sexually transmitted disease gonorrhea. An RND efflux pump [10,11,12,13,14,15,16] works in conjunction with a periplasmic membrane fusion protein [17,18,19,20], and an outer membrane channel to form a functional protein complex [21,22]. MtrE [24,25] is a 447 amino acid protein that forms an outer membrane channel.
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