Metabolic determinants in Listeria monocytogenes anaerobic listeriolysin O production
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ORIGINAL PAPER
Metabolic determinants in Listeria monocytogenes anaerobic listeriolysin O production Nathan Wallace1 · Eric Newton1 · Elizabeth Abrams1 · Ashley Zani1 · Yvonne Sun1
Received: 11 January 2017 / Accepted: 21 February 2017 © The Author(s) 2017. This article is published with open access at Springerlink.com
Abstract Listeria monocytogenes is a human pathogen and a facultative anaerobe. To better understand how anaerobic growth affects L. monocytogenes pathogenesis, we first showed that anaerobic growth led to decreased growth and changes in surface morphology. Moreover, compared to aerobically grown bacteria, anaerobically grown L. monocytogenes established higher level of invasion but decreased intracellular growth and actin polymerization in cultured cells. The production of listeriolysin O (LLO) was significantly lower in anaerobic cultures—a phenotype observed in wild type and isogenic mutants lacking transcriptional regulators SigB or CodY or harboring a constitutively active PrfA. To explore potential regulatory mechanisms, we established that the addition of central carbon metabolism intermediates, such as acetate, citrate, fumarate, pyruvate, lactate, and succinate, led to an increase in LLO activity in the anaerobic culture supernatant. These results highlight the regulatory role of central carbon metabolism in L. monocytogenes pathogenesis under anaerobic conditions. Keywords Anaerobic metabolism · Virulence regulation · Tricarboxylic acid cycle
Communicated by Erko Stackebrandt. * Yvonne Sun [email protected] 1
Department of Biology, University of Dayton, 300 College Park, Dayton, OH 45469, USA
Introduction Listeria monocytogenes is a foodborne pathogen and a leading cause of death from foodborne illnesses (Scallan et al. 2011). While immuno-competent individuals may develop mild gastroenteritis after ingestion of large amounts of L. monocytogenes, immuno-compromised individuals have a higher risk of developing systemic infections. These infections can cause more severe symptoms and lead to fatal outcomes despite early antibiotic treatments. Therefore, there is a need to better understand L. monocytogenes behavior during transmission to develop effective strategies to prevent infections. Upon ingestion, L. monocytogenes transits through the gastrointestinal tract and must adapt to host lumenal conditions to establish infections. However, despite the fact that the intestinal lumen is characterized by varying degrees of oxygenation (He et al. 1999), most of our understanding of L. monocytogenes pathogenesis is based on research conducted under aerobic conditions. The extent and the mechanism by which anaerobic exposure impacts L. monocytogenes pathogenesis are unclear. As a facultative anaerobe, L. monocytogenes can grow under strict anaerobic conditions with altered carbon metabolism. Chemical analyses have shown that in the presence of oxygen, L. monocytogenes incompletely oxidizes glucose to acetate, lactate, and acetoin. In the absence of oxygen, L. monocytogenes produces la
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