Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2013

Manganese starvation and compromised oxidative stress response are mediated by zinc toxicity in Streptococcus pneumoniae (#315)

Bart A Eijkelkamp 1 , Jacqueline R Morey 1 , Miranda P Ween 1 , Cheryl-lynn Ong 2 , Alastair G McEwan 2 , James C Paton 1 , Christopher A McDevitt 1
  1. University of Technology, Sydney, NSW, Australia
  2. University of Queensland, Brisbane, QLD, Australia

Streptococcus pneumoniae is one of the world’s most notorious bacterial pathogens responsible for more than 1 million deaths annually. The significant morbidity and mortality associated with pneumococcal infections result from inadequate vaccines and a rise in antibiotic resistance. Hence, an alternative strategy to target S. pneumoniae infections is required. Metal ions are essential micronutrients, however they can have toxic effects at high concentrations. We have recently determined the molecular basis of zinc toxicity in S. pneumoniae, and how it results in impaired manganese acquisition. Manganese is required for S. pneumoniae colonization of host tissues and the host exploits this by releasing zinc during infection as an immune defence. The S. pneumoniae mechanisms affected by manganese starvation remain poorly understood.

Here we show that in S. pneumoniae zinc toxicity results in hyper-susceptibility to oxidative stress due to loss of superoxide dismutase (SOD), the primary pneumococcal mechanism of protection against oxidative stress. Intriguingly, purified recombinant SOD was active with manganese and/or iron indicating that functionally it was a cambialistic SOD. However, despite this functional flexibility, in vivo analyses indicated that manganese was the physiological co-factor.

This study highlights the importance of manganese acquisition for resistance to oxidative stress, and survival within the host environment. Therefore, the pneumococcal manganese acquisition mechanisms may be suitable targets for novel treatment strategies.