The outcome would depend on which of the TPCA-1 in vitro strains was more fit. In the case of genetically marked strains of the same species with equal fitness we would expect to observe co-existence. In a series of pulse experiments with genetically marked colonizing (pulsed) and resident (established) strains we found the situation to be more complicated than this simple interpretation. For both H. influenzae and S. pneumoniae, the resident and the pulsed strains co-existed. Surprisingly in all replicates of these experiments, the invasion of a second selleckchem population of the same species was followed by an increase in the total bacterial density. Given that the steady-state

bacterial densities were independent of the initial inoculum density following a single inoculation, we had expected that the bacterial density after a second inoculation would decline to the original bacterial load. These results might be attributable to a second inoculation leading to an expansion DMXAA in the colonization area, increased immune suppression or the release of new resources – perhaps associated with an inflammatory response. On first consideration it would seem that the results of the S. aureus pulse experiments are consistent with classical ecological theory; the established population of this species inhibited the colonization of a new strain. Moreover, as expected following the

pulse by a second strain the total density of S. aureus returned to a level similar to that observed in the single inoculation experiments. However the resident strain had the advantage no matter which marker it carried (the competitive exclusion observed was not due to difference in fitness between the marked strains). We interpret these results as suggesting that S. aureus is limited by a localized resource

available on a ‘first-come, first-serve’ basis – perhaps attachment sites [28, 29]. This ecological hypothesis would account for the observations that competing strains of S. aureus were excluded from burn wounds [30] and from nasal colonization in persistent human carriers [31]. While these results do not exclude the possibility that variation within S. aureus strains may allow for coexistence as occasionally PJ34 HCl has been observed in humans [32], they do suggest that prior nasal colonization with S. aureus can exclude similar S. aureus strains from colonizing. Invasion of Different Species in a Colonized Host Ecologically, strains of different species would be anticipated to be more divergent than those of the same species and therefore they would be expected to occupy different niches. The results of our experiments are consistent with this interpretation as any pairwise combination of the three species can co-exist. While we had expected some sharing of resources by these different species, we found no evidence that the presence of one species reduced the density colonizing the nasal epithelium of another species.