ABSTRACT

Many cues, such as temperature, oxygen (O2), iron, pH, osmolarity and bicarbonate, allow bacteria to distinguish between environments within a host and outside of a host, as well as various microenvironments within a host [1]. In sensing multiple cues, bacteria are able to synchronize gene expression to adapt and ultimately thrive [2]. One cue, carbon dioxide (CO2), has been shown to affect regulation of virulence factor expression in many bacterial pathogens. Bacillus anthracis responds to elevated levels of CO2 by increasing expression of the genes encoding edema toxin, lethal factor and protective antigen [3]–[5]. In response to 10% CO2, Streptococcus pyogenes increases transcription of M protein, an important virulence factor that prevents the deposition of complement onto the bacterial surface [6]. In increased CO2, M protein has been shown to be regulated by a trans-acting positive regulatory protein that binds to the

is not increased transcriptionally in response to growth in CO2 [3]. Additionally, Staphylococcus aureus, Salmonella enterocolitica and Borrelia burgdorferri are responsive to increased CO2 concentrations, suggesting this ability is useful to a variety of pathogens [8]–[11].