Abstract
Bacteria use two-component systems (TCSs) to sense and respond to environmental changes. The core genome of the major human pathogen Staphylococcus aureus encodes 16 TCSs, one of which (WalRK) is essential. Here we show that S. aureus can be deprived of its complete sensorial TCS network and still survive under growth arrest conditions similarly to wild-type bacteria. Under replicating conditions, however, the WalRK system is necessary and sufficient to maintain bacterial growth, indicating that sensing through TCSs is mostly dispensable for living under constant environmental conditions. Characterization of S. aureus derivatives containing individual TCSs reveals that each TCS appears to be autonomous and self-sufficient to sense and respond to specific environmental cues, although some level of cross-regulation between non-cognate sensor-response regulator pairs occurs in vivo. This organization, if confirmed in other bacterial species, may provide a general evolutionarily mechanism for flexible bacterial adaptation to life in new niches.
Highlights
Bacteria use two-component systems (TCSs) to sense and respond to environmental changes
Taking all the above into account, we selected S. aureus to investigate the following questions related to the TCS network: (i) which is the minimal number of TCSs needed to sustain life in a free-living bacteria?; (ii) are TCSs self-sufficient and autonomous entities?; and (iii) does TCSs cross talk occur in vivo?
We initiated this study in an attempt to confirm the essentiality of TCSs for bacterial survival by removing the complete TCS network from S. aureus
Summary
Removal of the complete TCS network from S. aureus. We initiated this study in an attempt to confirm the essentiality of TCSs for bacterial survival by removing the complete TCS network from S. aureus. Analysis of the metabolic capacities using API test revealed that S. aureus ΔXV strains exhibited a deficiency only in the capacity to reduce nitrate to nitrite (Fig. 2c and Supplementary Fig. 2b) In agreement with these results, a global metabolomic profile showed that the removal of the TCS network caused significant differences in the concentration of only a few metabolites (Supplementary Data 1). The expression of virulence factors (protein A and hemolysins) was significantly reduced in ΔXV strains (Fig. 2i, j and Supplementary Fig. 2f, g) Taken together, these results confirmed that TCS signaling systems allow free-living bacteria to adapt to different environmental conditions, including life in animal hosts. Two-component systems wal hpt lyt gra sae tcs[7] arl srr pho air vra agr kdp hss nre bra WT
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