December 11, 2017 – 17.15 h | Seminar room N260/3.13
Abstract: Acinetobacter baumannii is an important nosocomial pathogen that accounts for a significant percentage of infections in intensive care units worldwide. Furthermore, A. baumannii strains have emerged that are resistant to all available antimicrobials. These facts highlight the need for new therapeutic strategies to combat this growing public health threat. Given the critical role for transition metals at the pathogen-host interface, interrogating the role for these metals in A. baumannii physiology and pathogenesis could elucidate novel therapeutic strategies. Toward this end, my laboratory is interrogating the impact of host metal binding proteins in defense against A. baumannii pneumonia, and the bacterial factors that compete with this powerful host defense. In particular, we are interested in the neutrophil protein calprotectin (Cp) that inhibits microbial growth through the chelation of nutrient manganese (Mn) and zinc (Zn). We have found that CP accompanies neutrophil recruitment to the lung and accumulates at foci of infection in a murine model of A. baumannii pneumonia. CP contributes to host survival and control of bacterial replication in the lung and limits dissemination to secondary sites. Furthermore, we discovered that A. baumannii coordinates transcription of an NRAMP family Mn transporter and a urea carboxylase to resist the antimicrobial activities of metal chelation. We have also found that this system combats CP in vivo. These findings reveal that A. baumannii has evolved mechanisms to subvert host-mediated metal sequestration and they uncover a connection between metal starvation and metabolic stress.
When: December 11, 2017 – 17.15 h
Where: Seminar room N260/3.13
Related Publication: Kinsella RL, Lopez J, Palmer LD, Salinas ND, Skaar EP, Tolia NH, Feldman MF. Defining the interaction of the protease CpaA with its type II secretion-chaperone CpaB and its contribution to virulence in Acinetobacter species. The Journal of biological chemistry. 2017 Oct 5. PMID: 28982978 [PubMed]