Bactericidal disruption of magnesium metallostasis in Mycobacterium tuberculosis is counteracted by mutations in the metal ion transporter CorA

A defining characteristic of treating tuberculosis is the need for prolonged administration of multiple drugs. This may be due in part to subpopulations of slowly replicating or nonreplicating Mycobacterium tuberculosis bacilli exhibiting phenotypic tolerance to most antibiotics in the standard treatment regimen. Confounding this problem is the increasing incidence of heritable multidrug-resistant M. tuberculosis. A search for new antimycobacterial chemical scaffolds that can kill phenotypically drug-tolerant mycobacteria uncovered tricyclic 4-hydroxyquinolines and a barbituric acid derivative with mycobactericidal activity against both replicating and nonreplicating M. tuberculosis. Both families of compounds depleted M. tuberculosis of intrabacterial magnesium. Complete or partial resistance to both chemotypes arose from mutations in the putative mycobacterial Mg2+/Co2+ ion channel, CorA. Excess extracellular Mg2+, but not other divalent cations, diminished the compounds’ cidality against replicating M. tuberculosis. These findings establish depletion of intrabacterial magnesium as an antimicrobial mechanism of action and show that M. tuberculosis magnesium homeostasis is vulnerable to disruption by structurally diverse, nonchelating, drug-like compounds

Sport as a means of immigrant youth integration: An empirical study of sports, intercultural relations, and immigrant youth integration in Switzerland

Der Beitrag geht der Bedeutung des Sports für die Integration von jugendlichen Einwanderern in die Aufnahmegesellschaft nach. Aufgrund von Daten einer Querschnittstudie bei 454 Jugendlichen der ersten Einwanderergeneration aus Gymnasien, Berufsschulen und Vorlehreeinrichtungen der deutschen Schweiz zeigen unsere Ergebnisse, dass der Sport für die meisten Jugendlichen mit Migrationshintergrund ein wichtiger Teil ihrer Freizeit darstellt, auch wenn der Anteil von Migrantinnen, die Mitglied eines Sportvereins sind, im Vergleich zu Migranten zweimal niedriger ausfällt. Zudem haben sowohl männliche wie weibliche Jugendliche mit Migrationshintergrund, die Sport in einem Sportverein ausüben, deutlich mehr persönliche Kontakte mit Schweizer Peers während ihrer sportlichen Aktivitäten. Jugendliche, die von häufigen persönlichen Kontakt mit Schweizer Peers im Sport berichten, haben auch deutlich mehr interkulturelle Kontakte in ihrer Freizeit generell und innerhalb des Kreises ihren engsten Freunde. Schließlich vermögen häufige Kontakte mit Schweizer Peers im Sport das Gefühl der jugendlichen Einwanderer, in der Schweiz integriert zu sein, zu erhöhen.The objective of this paper is to examine the role of sport in immigrant youths’ integration into a host society. The analyses are based on a survey of 454 first-generation immigrant youths from secondary, vocational, and pre-apprenticeship schools located in the German-speaking part of Switzerland. In short, our results indicate that for most immigrant youth sport is an important part of their free time, even though the proportion of female immigrant youth doing sports in sports clubs is twice as low as that of male immigrant youth. Our findings also illustrate that female and male immigrant youth who do sports in clubs have considerably more personal contact with Swiss peers during these sporting activities. Moreover, those young people who have frequent personal contact with Swiss peers during sporting activities reported having considerably more intercultural contacts in their free time and among their close friends. Finally, immigrant youths’ contacts with Swiss peers during sporting activities increase their feeling of being integrated in Switzerland