Table 1.

Hypothesized changes in the interactions for co-infections with mutant strains of NTHi and Mcat. For each set of co-infected strains, we indicate the hypothesized changes in the four interaction parameters as suggested by the published literature. An open, dashed circle () indicates no change. A filled circle () indicates an increase. A small, open circle () indicates a decrease, and a bull's-eye () indicates the parameter could increase or decrease. As shown in figure 1a, the LV interaction parameters α₁₁ and α₂₂ represent the strength of NTHi's and Mcat's self-inhibition, respectively. The α₁₂ parameter represents the interaction of Mcat on NTHi, and α₂₁ represents the inverse. For the latter two, a decreasing (or more negative) value indicates cooperation, while an increasing (or more positive) value indicates competition.

co-infecting strains	hypothesized changes in the interactions α11 α12 α21 α22	justification
NTHi (wt) + Mcat (hag)		The hag mutation decreases adhesion of Mcat to the substrate and results in poor biofilm formation [20,21]. This mutant could lead to lower biomass or decreased carrying capacity (or higher α22) for Mcat.
NTHi (wt) + Mcat (mcaB)		The mcaB mutant is unable to sense the AI-2 molecules secreted by NTHi (Li et al., unpublished data). Thus, this Mcat mutant will experience less cooperation from NTHi, or increased values of α21.
NTHi (wt) + Mcat (aaa)		The aaa mutant has the Hag programme constitutively on (Li et al., unpublished data). Therefore, it makes dense biofilms without any help from NTHi and has a larger carrying capacity or decreased value of α22.
NTHi (luxS) + Mcat (wt)		The luxS mutant is unable to produce AI-2, produces less dense biofilms and as a result causes more acute disease with higher levels of early inflammation. Thus the mutant can produce lower cooperation to Mcat (higher α21) due to the lack of quorum sensing, and lower values of carrying capacity (higher α11) due to poor biofilm quality [22]. However, the increased inflammation could provide nutrients for self-growth (lower α11) or Mcat growth (lower α21).
NTHi (wt) + Mcat (mclR)		The mclR mutant does not respond to NTHi quorum sensing and forms poor biofilms (Li et al., unpublished data). Thus, Mcat will receive less cooperation from NTHi (higher α21) and give less cooperation to NTHi (higher α12).
NTHi (wt) + Mcat (dtgt)		The dtgt mutant is unable to respond to quorum signals from NTHi and also has a mutation in the hag promoter. The latter effect disrupts Mcat production of this adhesion protein and thus adhesion to the substrate (presumably host epithelia but also potentially aggregation with other bacteria) (Li et al., unpublished data). Thus, the mutant receives less cooperation from NTHi (higher α21) and has a lower carrying capacity (higher α22).
NTHi (luxS) + Mcat (mcaB)		As described above for the NTHi (luxS) mutant, α11 and α21 may either increase or decrease, whereas for the Mcat (mcaB) mutant, α21 increases. Because of the latter mutation, we hypothesize an increase in α21.
NTHi (luxS) + Mcat (hag)		As described above for the luxS mutant, α11 and α21 can either increase or decrease depending on the existing conditions. α22 will increase based on the hag mutant as mentioned above.
NTHi (luxS) + Mcat (dtgt)		As described above for the luxS and dtgt mutants, α11 and α21 can either increase or decrease depending on the existing conditions, and α22 will increase.
NTHi (luxS) + Mcat (aaa)		As described above for the luxS mutant, α11 and α21 can either increase or decrease depending on the existing conditions. α22 will decrease based on the aaa mutant as mentioned above.
NTHi (luxS) + Mcat (mclR)		As described above for the NTHi (luxS) mutant, α11 and α21 can either increase or decrease, whereas for Mcat (mclR) mutant, α21 increases. Because of the latter mutation, we hypothesize an increase in α21.