"Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection." 

Wilde A.D. et al., PLoS Pathog, 2015 Dec 18. Dec 11(12): e1005341

• Infection of the bone (Osteomyelitis) is one of the most common manifestations of S. aureus invasive infection. Bone is naturally hypoxic, requiring S. aureus to adapt to a low oxygen environment during infection. In the featured work by Wilde et al., employed Transposon Sequencing analysis (TnSeq), a technique that combines saturated transposon mutant libraries with massively parallel sequencing to identify genes required under an experimentally induced selective pressure. 
  
  
• Using this technique, Wilde et al., identified over 200 genes required for invasive osteomyelitis. Of these, a bacterial two component system, SrrAB, known to be important for responding to hypoxic and nitrosative stresses was identified as critical.
  
  
• Oxygen concentration measurements in the bone during experimental osteomyelitis, revealed that the bone becomes increasingly hypoxic during infection.
  
  
• In vitro studies subsequently determined that hypoxic growth of S. aureus significantly increases quorum sensing-dependent toxin production and that, conversely, aerobic growth suppresses quorum-dependent toxin production. This suppression is dependent upon SrrAB.
  
  
  
• Significance: While most studies investigating host-pathogen interactions are performed with rapidly growing cultures and - if appropriate - under atmospheric oxygen conditions, almost all bacterial pathogens grow at a much slower rate and experience lower oxygen concentrations during infection in the host. Studies like the ones described by Wilde et al., most closely interrogate physiologically relevant bacterial responses