Examples of melting curves for each target region

<p>. For some target regions not all melting curves were represented among the isolates analysed in this study, therefore not all theoretically possible curves are depicted in the figure. <b>A</b>) Target region <i>infB</i>729, showing two (12, 13) of two predicted melting curves. <b>B</b>) Target region <i>mdh</i>1197, showing two (9, 10) of three predicted melting curves. <b>C</b>) Target region <i>pho</i>E2013, showing four (18, 19, 20, 21) of four predicted melting curves. <b>D</b>) Target region <i>rpoB</i>2227, showing six (41, 42 43, 44, 45, 46) of seven predicted melting curves. <b>E</b>) Target region <i>tonB</i>2693, showing three (39, 40, 41) of seven predicted melting curves. <b>F</b>) Target region <i>tonB</i>2886, showing three (54, 55, 56) of eight predicted melting curves.</p

Power of Minim typing to identify and discriminate <i>K. pneumoniae</i> STs of particular significance.

<p>*SLV = single locus variant, DLV = double locus variant, TLV = triple locus variant, QLV = quadruple locus variant.</p

Discriminatory power from different combinations of markers, calculated against all STs (863 STs, <i>D</i> = 1).

<p>Discriminatory power from different combinations of markers, calculated against all STs (863 STs, <i>D</i> = 1).</p

Indices of association for combinations of MLST alleles with and without <i>tonB</i>, and measurements of diversity conferred by individual loci indicate that <i>tonB</i> is highly diverse and likely subjected to horizontal gene transfer.

<p>Indices of association for combinations of MLST alleles with and without <i>tonB</i>, and measurements of diversity conferred by individual loci indicate that <i>tonB</i> is highly diverse and likely subjected to horizontal gene transfer.</p

Biotin Analogues with Antibacterial Activity Are Potent Inhibitors of Biotin Protein Ligase

There is a desperate need to develop new antibiotic agents to combat the rise of drug-resistant bacteria, such as clinically important <i>Staphylococcus aureus</i>. The essential multifunctional enzyme, biotin protein ligase (BPL), is one potential drug target for new antibiotics. We report the synthesis and characterization of a series of biotin analogues with activity against BPLs from <i>S. aureus</i>, <i>Escherichia coli</i>, and <i>Homo sapiens</i>. Two potent inhibitors with <i>K</i>_i < 100 nM were identified with antibacterial activity against a panel of clinical isolates of <i>S. aureus</i> (MIC 2–16 μg/mL). Compounds with high ligand efficiency and >20-fold selectivity between the isozymes were identified and characterized. The antibacterial mode of action was shown to be via inhibition of BPL. The bimolecular interactions between the BPL and the inhibitors were defined by surface plasmon resonance studies and X-ray crystallography. These findings pave the way for second-generation inhibitors and antibiotics with greater potency and selectivity