Insight into Two ABC Transporter Families Involved in Lantibiotic Resistance

Antimicrobial peptides, which contain (methyl)-lanthionine-rings are called lantibiotics. They are produced by several Gram-positive bacteria and are mainly active against these bacteria. Although these are highly potent antimicrobials, some human pathogenic bacteria express specific ABC transporters that confer resistance and counteract their antimicrobial activity. Two distinct ABC transporter families are known to be involved in this process. These are the Cpr- and Bce-type ABC transporter families, named after their involvement in cationic peptide resistance in Clostridium difficile, and bacitracin efflux in Bacillus subtilis, respectively. Both resistance systems differentiate to each other in terms of the proteins involved. Here, we summarize the current knowledge and describe the divergence as well as the common features present in both the systems to confer lantibiotic resistance

Evaluation of sexual dimorphism using permanent maxillary first molar in Sri Ganganagar population

Aim of Study: The aim is to evaluate existence of sexual dimorphism by variation in right and left permanent maxillary molars using buccolingual width (BLW) and mesio-distal width (MDW) measured intraorally and on study casts among Sri Ganganagar population. Materials and Methods: Fifty patients (25 males and 25 females) with 17–25 years of age were selected. Impressions of maxillary arch were taken and the BLW and MDW were measured using digital Vernier calipers on study casts and intraorally. Results: Highly significant correlation was found between MDW and BLW of both the maxillary permanent first molars for both genders (P < 0.05) intraorally. The MDW and BLW on study cast of both sides in both gender were more on left side in males while on right side in females. Conclusion: Left maxillary permanent first molar showed minimum mean difference of measurements on study cast and introrally than right, thus better predictor for gender dimorphism in forensics

Location of the highly conserved Asp55 and inactive state conformation of the key switch residues, Ser82 and Phe101 in NsrR-RD.

<p>NsrR (represented in yellow) displays a geometry representing the inactive state as deduced from the inactive state structure of PhoB (shown in brown, PDB code 1B00) (a). The inactive conformation of NsrR differs from the active state structure of PhoB (light blue, PDB code 1ZES) (b) in the orientation of the corresponding switch residues, Ser82 and Phe101, which adopt a conformation pointing away from the active site (Asp55 in NsrR).</p

Sequence alignment of NsrR protein with other response regulators.

<p>A sequence alignment of NsrR with RRs belonging to the OmpR/PhoB subfamily (marked in grey) and RRs involved in lantibiotic resistance (black) is shown. The active site aspartate residue (highlighted in red), the residues forming the acidic pocket surrounding it (highlighted in pink), the switch residues (highlighted in blue), the conserved lysine residue (highlighted in green), the highly conserved residues of the linker region (colored in purple), the residues involved in dimer interface of receiver domain (highlighted in yellow), residues involved in interdomain interactions (shown in orange boxes and in cyan) and the residues involved in interaction with DNA (colored in blue) are shown. The linker region of the known structures is underlined within the sequence.</p

Structure of NsrR-RD.

<p>Cartoon representation of the helices (α1 – α5) and β-sheets (β1 - β5). Structural areas with the highest variations to the receiver domains of DrrB (pink, 1P2F), MtrA (grey, 2GWR), and PhoB (blue, 1B00) are marked in separate boxes.</p

Data collection, phasing, and refinement statistics for the receiver and effector domains of NsrR.

<p>Data collection, phasing, and refinement statistics for the receiver and effector domains of NsrR.</p

Purification of NsrR and SDS PAGE analysis of purified NsrR directly and one week after purification.

<p>(a) Elution profile of size-exclusion chromatography step of NsrR. The y-axis represents the UV absorption of the protein at 280 nm, while the x-axis represents the elution volume. a, b, c refer to the protein standards dextran blue (2,000 kDa), BSA (67 kDa), and lysozyme (14.3 kDa), respectively. The bold line represents the chromatogram of freshly purified NsrR while the dashed line shows the chromatogram of the same NsrR protein after one week. (b) Freshly purified NsrR protein, and (c) NsrR protein after one week. Lanes: M represents the PAGE Ruler Unstained Ladder; 1: NsrR after a two-step purification; 2: NsrR one week after purification. * corresponds to full-length NsrR protein at 27 kDa, while ** and *** correspond to the NsrR-RD and NsrR-ED domain at around 13 kDa, respectively.</p

The structures of the RD and ED domains of NsrR aligned to other response regulators.

<p>The rmsd values of the superimpositions of the structures of NsrR-RD and NsrR-ED with the available structures of members of the OmpR/PhoB subfamily are highlighted. *Seq ID (%) corresponds to the full-length protein sequence.</p

Functional dimer orientation of the RDs of NsrR.

<p>Dimeric structure of the RD of NsrR aligned to the structure of KdpE (PDB code 1ZH2, not shown). (a) The two monomers of NsrR as functional dimers are represented in a cartoon representation displayed in cyan and yellow colors. (b) Zoom-in of the dimeric interface mediated by α4-β5-α5. The monomer-monomer interactions are facilitated by hydrophobic residues (displayed as spheres), inter- and intra-domain interactions (displayed as sticks). The layout is adopted from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149903#pone.0149903.ref055" target="_blank">55</a>].</p