ABC Exporters in Pathogenesis: Role of Synthetic Anti-Microbial Peptides
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ABC Exporters in Pathogenesis: Role of Synthetic Anti‑Microbial Peptides Ritika Kabra1 · Shailza Singh1 Accepted: 12 October 2020 / Published online: 17 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract ABC exporters are involved in diverse cellular processes including lipid trafficking, drug resistance, pathogenesis etc. The greatest thrust has been in the area of drug resistance that explains the underlying well-crafted canonical architecture of its structure. Interestingly, ranging from structural organisation to subsequent design and delivery aspects lays the niche of antimicrobial peptides. One of the major highlight of this paper is the role of synthetic antimicrobial peptides in current scenario. Keywords ABC · Synthetic AMPs · Antibacterial resistance Abbreviations ABC ATP binding cassette ALD Adrenoleukodystrophy AMPs Antimicrobial peptides CFTR Cystic fibrosis transmembrane conductance regulator MATE Multidrug and toxin compound extrusion MDR Multi drug resistance MFS Major facilitator superfamily MMP7 Matrix metalloproteinase 7 NBD Nucleotide binding domain OABP Organic anion binding protein PACE Proteobacterial antimicrobial compound efflux PXE Pseudoxanthoma elasticum RND Resistance nodulation division SMR Small multidrug resistance SUR Sulfonylurea receptor TAP Transporters associated with antigen processing TMD Transmembrane domain TMH Transmembrane helices
* Shailza Singh [email protected]; [email protected] 1
National Centre for Cell Science, NCCS Complex, Ganeshkhind, Pune 411007, India
1 Introduction An emerging crisis all over the world is a large number of antimicrobial drugs becoming ineffective against most microbes due to emergence of resistance. It has been observed that most of the microbes are exhibiting insensitivity for more than one drug, a condition termed as Multi Drug Resistance (MDR). Studies have concluded that occurrence of resistance, mainly in bacteria, is mostly because of one or combination of the two mechanisms. First, expression of multiple genes responsible for resistance to a single or multiple drugs in a cell. Second, increased activity or overexpression of efflux proteins (or exporters) [1–3]. The efflux proteins are classified into six major classes namely small multidrug resistance (SMR), proteobacterial antimicrobial compound efflux (PACE), major facilitator superfamily (MFS), multidrug and toxin compound extrusion (MATE), resistance nodulation division (RND) and ATP binding cassette (ABC) superfamily. Of these, ABC superfamily is the largest [4]. In order to solve the resistance issues, ABC exporters have always been the desired target protein. Great efforts have been taken in either inhibiting or modulating them. But the major obstacles in their success was their high level of conservedness resulting in toxicity and gradual ineffectiveness of inhibitors due to rapid rate of mutations [5, 6]. With the failure of first and second line of drugs against Multi drug resistant microbes, due to either
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