Magnesium Links Starvation-Mediated Antibiotic Persistence to ATP

ABSTRACT Bacterial persisters emerge and increase in numbers over time as a bacterial culture grows from log phase to stationary phase. However, the underlying basis of the inevitable tendency is unclear. In this study, we investigated the role of nutrients in starvation-mediated persister formation of Staphylococcus aureus. By screening of nutrient components, we found that starvation-induced persister formation of log-phase cultures could be reversed by addition of magnesium (Mg2+) but not amino acids, nucleotides, or other salts. Further, deprivation of extracellular Mg2+ reduced cytoplasmic ATP, inducing persistence without affecting cytoplasmic Mg2+ or membrane potential. Finally, we showed that Mg2+ reduced expression of stationary cell marker genes, cap5A and arcA. These findings indicate a connection between Mg2+ levels and ATP, which represents metabolic status and mediates antibiotic persistence during growth. IMPORTANCE Various genes have been identified to be involved in bacterial persister formation regardless of the presence or absence of persister genes. Despite recent discoveries of the roles of ATP and membrane potential in persister formation, the key element that triggers change of ATP or membrane potential remains elusive. Our work demonstrates that Mg2+ instead of other ions or nutrient components is the key element for persistence by inducing a decrease of cytoplasmic ATP, which subsequently induces persister formation. In addition, we observed tight regulation of genes for Mg2+ transport in different growth phases in S. aureus. These findings indicate that despite being a key nutrient, Mg2+ also served as a key signal in persister formation during growth.

CONCENTRATION AND PURIFICATION OF THE PECTIN EXTRACTS BY ULTRAFILTRATION METHOD

The work is devoted to the study of pectin extracts ultrafiltration using different types of membranes. Pectic extracts are the solutions of high molecular weight polysaccharides (MM from 15 to 50 kDa), which are destroyed in the process of heat treatment in the vacuum evaporating apparature, that leads to a significant deterioration in the quality of pectin. The impurity components in the pectin extract of a low molecular weight, which makes it possible to use ultrafiltration for both concentration and purification from ballast substances, that is very important. The objects of research were pectin extracts obtained from citrus raw materials; the membranes of the type UAM-100 and 200A were used as filter membranes. The results of the study have been shown, that the use of UAM-100 membranes in a stationary cell allows to remove up to 20% of the solution within 20 minutes, and with - stirring up to 27%. The use of membranes with large openings (up to 200 A) makes it possible to activate the process of the separation and concentration of pectin extracts: the degree of concentration reaches up 45%, the content of solids in the concentrate increases up to 7.6%, and the content of pectin to up 6.4%, that is in 1,7 times. However, the loss of low molecular weight pectin in the filtrate is about 4%. A comparative analysis of the results of research has shown a high productivity with the use of the capron membrane 200A, as well as on the qualitative parameters of the pectins, released from the concentrates, the higher parameters for the uroconid component, molecular weight, pectin jelly strength and complexing ability were noted for pectins isolated using the UAM- 100 membrane.