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Title: The ecology of Staphylococcus aureus
Author: Libberton, Andrew Benjamin
ISNI:       0000 0004 2737 1741
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2011
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Nasal carriage of Stephvtococcue aureus is associated with increased risk of infection in humans. Several factors are known to affect carriage including host genetics and S. aureus immune evasion. However while members of the microbial community have been shown to affect S. aureus nasal colonisation individually, relatively little work has been done to understand how and why nasal microbial community as a whole, affects carriage of S. aureus. Here, the cultivable bacteria from 60 anterior nares communities were sampled and identified to species level using apiSTAPH and 16S rRNA gene sequencing. The taxa distributions across communities revealed negative associations of S. aureus with the following taxa: S. capitis, Corynebacterium propinquum, C. macgin/eyi, Enterobacter aerogenes, S. epidermidis, Micrococcus sp., Bacillus sp., C. acco/ens, S. schleiferi and Gemella haemo/ysans. Since toxin-mediated interference can affect community composition, nasal isolates were screened for their ability to inhibit growth of S. aureus on a solid medium. Overlaying this inhibition data onto community taxa distributions revealed that negative associations between S. aureus and S. epidermidis, S. capitis, C. propinquum, C. acco/ens and a Micrococcus sp. were potentially driven by toxin- mediated interference competition. Moreover novel negative associates were found between S. aureus and an inhibitory subset of Micrococcus /uteus and S. hominis. By also measuring the cumulative inhibition of entire natural communities, it was possible to show that S. aureus was less frequent in highly inhibitory microbial communities. The quorum sensing mechanism, encoded by the agr locus, and biofilm formation have been proposed to play an important role in nasal colonisation of S. aureus. Therefore to further investigate community dynamics, S. capitis, S. epidermidis and corynebacteria isolates were assayed for their ability to interfere with Agr signaling and biofilm formation. No evidence was obtained to indicate that biofilm interference by these species affected the distribution of S. aureus across communities. By contrast, S. epidermidis isolates that interfered with Agr signaling were significantly more likely to coexist with S. aureus, and S. capitis isolates interfering with Agr signaling were significantly less likely to coexist with S. aureus. In theory, toxin-mediated interference competition can act both to protect producers against invasion, and, conversely, to promote the invasion of producers into an occupied niche. An experimental ecology approach was used to show that S. aureus is less likely to invade an inhibitor-producing S. epidermidis population than a non-inhibitor-producing population, especially on a spatially-structured medium. Furthermore, inhibitor-producing populations of S. epidermidis invade more successfully than non-inhibitor-producers, although they do not displace the S. aureus resident due to evolution of toxin resistance. There is also evidence of eo- evolution where inhibitor-producing strains of S. epidermidis can evolve stronger inhibitory activity when invading sensitive S. aureus populations that evolve resistance. These findings could impact the future treatment of S. aureus infections and help to control nasal carriage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral