Use this URL to cite or link to this record in EThOS:
Title: Comparative genomics of the skin staphylococci
Author: Coates-Brown, Rosanna
ISNI:       0000 0004 6058 0561
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2015
Availability of Full Text:
Access from EThOS:
Access from Institution:
The human skin is a complex ecosystem which supports a diverse population of bacteria. Comparative genomic analyses are increasingly being used to explore the functional potential of this bacterial population . The ubiquity of Staphylococcus on human skin means this genus represents the most well-studied of the microbial skin residents, however most analysis has focussed on the significant clinical pathogenic species S. epidermidis and S. aureus. To investigate the biology of S. hominis, the second most frequent Staphylococcus species isolated from human skin after S. epidermidis, seven isolates were sequenced using Illumina and PacBio technologies. An intraspecies comparative genomic analysis was performed with these and several publically available S. hominis genomes to identify core and accessory genes. The complement of encoded cell wall-anchored proteins was studied using bioinformatics to describe the range of surface-attached proteins and revealed a unique species set. Investigation also revealed the presence of S. hominis genes described as virulence factors in S. aureus and S. epidermidis. This further highlights non-pathogenic staphylococci as a reservoir of genes, which can be exchanged with pathogenic S. aureus, and the potential for recruitment of these genes into virulence pathways. Interspecies comparative analysis of twenty Staphylococcus species, based on clusters of orthologous genes, confirmed the designation of staphylococcal species groups previously established by DNA-DNA hybridisation and single gene analysis methods. The bioinformatic algorithm randomForest was used to identify drivers forming species groups based on the orthologous gene cluster analysis leading to a subset of orthologous clusters defined as being contributory. This interspecies analysis also revealed diversity between the staphylococcal species groups with respect to their response mechanisms for antimicrobial peptide (AMP) resistance. Specifically, the presence or absence of the BraRS two-component system (TCS) was identified to be one of the important drivers differentiating a nine species member group that included S. aureus, S. hominis and S. epidermidis. Experimental evolution in the presence of the lantibiotic nisin was used to dissect differences in the global response of the BraRS-positive species S. hominis and S. aureus, from the BraRS-negative species S. saprophyticus, . Identified SNPs from the resistance evolution revealed complex relationships between the regulons of staphylococcal TCSs and identified that YurK should be investigated for a potential role in AMP resistance of S. aureus and S. hominis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available