Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Investigation of the roles of cytoplasmic enzymes in zinc toxicity to the pathogenic organism Streptococcus pneumoniae. (#235)

Mwilye Sikanyika 1 , Christopher CAM McDevitt 2 , David Aragao 3 , Megan MJM Maher 1
  1. School of Molecular Biosciences, La Trobe University, Bundoora, Victoria, Australia
  2. School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia
  3. Australian Synchrotron , Clayton, VIC, Australia

Streptococcus pneumoniae is a gram positive, facultative anaerobic bacterium and is the leading bacterial cause of pneumonia, meningitis and sepsis [1]. Upon infection by the bacterial pathogen S. pneumoniae, the host innate immune response oversaturates the infection site with high concentrations of zinc causing a phenomenon called zinc toxicity.

The molecular basis of Zn toxicity in S. pneumoniae, is still currently being elucidated. One well-established mechanism involves the inhibition of Mn2+ uptake by Zn2+ through its irreversibly binding to the PsaBCA transporter [2]. Zn toxicity is known to increase oxidative stress in S. pneumoniae due to the inhibition of Mn uptake [3]. However, it is also known that Zn toxicity can causee oxidative stress via disruptions of many intracellular pathways [3], implying that the metal has additional mechanisms of action beyond its inhibition of Mn2+ transport.

This poster will present our recent progress in the characterization of intracellular targets of metal toxicity and the specific mechanisms of action, both from a structural and functional point of view.

  1. Jacobs MR, Good CE, Bajaksouzian S, Windau AR (2008) Emergence of Streptococcus pneumoniae serotypes 19A, 6C, and 22F and serogroup 15 in Cleveland, Ohio, in relation to introduction of the protein-conjugated pneumococcal vaccine. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 47: 1388-1395
  2. McDevitt CA, Ogunniyi AD, Valkov E, Lawrence MC, Kobe B, McEwan AG, Paton JC (2011) A molecular mechanism for bacterial susceptibility to zinc. PLoS Pathog. 7, e1002357
  3. Eijkelkamp BA, Morey JR, Ween MP, Ong C.-LY, McEwan AG, Paton JC, and McDevitt CA (2014) Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae. PLoS ONE 9: e89427.