Model depicting the role of Mn2+ and Zn2+ in the regulation of the RpoS pathway through BosR. Expression of rpoS is modulated by two transcriptional factors, Rrp2 and BosR. Rrp2 activity is modulated via phosphorylation by acetyl∼P or Hk2 (80, 99). For the purpose of simplification, factors that influence RpoS through acetyl∼P such as CsrA, OppA5, acetate, and the mevalonate pathway are not included in the model (63, 80, 84–86). Environmental and host signals, such as temperature and blood, can modulate rpoS expression by altering the intracellular Mn2+ and Zn2+ status and subsequently BosR levels. A low intracellular Mn2+ and high Zn2+ status promotes a high level of BosR protein (not bosR transcript), leading to the increased level of RpoS and RpoS-controlled products such as OspC. In addition, temperature can also regulate RpoS levels via small RNA DsrA at low cell density (26).