Re-evaluation of the significance of penicillin binding protein 3 in the susceptibility of Listeria monocytogenes to β-lactam antibiotics

<p>Abstract</p> <p>Background</p> <p>Penicillin binding protein 3 (PBP3) of <it>L. monocytogenes </it>has long been thought of as the primary lethal target for β-lactam antibiotics due to the excellent correlation between the MICs of different β-lactams and their affinity for this protein. The gene encoding PBP3 has not yet been directly identified in this gram-positive bacterium, but based on <it>in silico </it>analysis, this protein is likely to be encoded by <it>lmo1438</it>. However, studies examining the effects of mutations in genes encoding known and putative <it>L. monocytogenes </it>PBPs have demonstrated that inactivation of <it>lmo1438 </it>does not affect sensitivity to β-lactams.</p> <p>Results</p> <p>In this study, overexpression of <it>lmo1438 </it>was achieved using an inducible (nisin-controlled) expression system. This permitted the direct demonstration that <it>lmo1438 </it>encodes PBP3. PBP3 overexpression was accompanied by slightly elevated PBP4 expression. The recombinant strain overexpressing PBP3 displayed significant growth retardation and greatly reduced cell length in the stationary phase of growth in culture. In antibiotic susceptibility assays, the strain overexpressing PBP3 displayed increased sensitivity to subinhibitory concentrations of several β-lactams and decreased survival in the presence of a lethal dose of penicillin G. However, the MIC values of the tested β-lactams for this recombinant strain were unchanged compared to the parent strain.</p> <p>Conclusions</p> <p>The present study allows a reevaluation of the importance of PBP3 in the susceptibility of <it>L. monocytogenes </it>to β-lactams. It is clear that PBP3 is not the primary lethal target for β-lactams, since neither the absence nor an excess of this protein affect the susceptibility of <it>L. monocytogenes </it>to these antibiotics. The elevated level of PBP4 expression observed in the recombinant strain overexpressing PBP3 demonstrates that the composition of the <it>L. monocytogenes </it>cell wall is subject to tight regulation. The observed changes in the morphology of stationary phase cells in response to PBP3 overexpression suggests the involvement of this protein in cell division during this phase of growth.</p

Wealth rheology

We study wealth rank correlations in a simple model of macro-economy. To quantify rank correlations between wealth rankings at different times, we use Kendall's $\tau$ and Spearman's $\rho$, Goodman--Kruskal's $\gamma$, and the lists' overlap ratio. We show that the dynamics of wealth flow and the speed of reshuffling in the ranking list depend on parameters of the model controlling the wealth exchange rate and the wealth growth volatility. As an example of the rheology of wealth in real data, we analyze the lists of the richest people in Poland, Germany, the USA and the world.Comment: 13 pages, 5 figures, for "Entropy and Social Physics", https://www.mdpi.com/journal/entropy/special_issues/Social_Physic