The role of the mobilome in the evolution and host-adaptation of Streptococcus agalactiae

Crestani, Chiara (2021) The role of the mobilome in the evolution and host-adaptation of Streptococcus agalactiae. PhD thesis, University of Glasgow.

Abstract

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a complex multihost opportunistic bacterial pathogen. In human medicine it is recognised as a leading invasive neonatal pathogen, an emerging pathogen of non-pregnant adults and a newly-emerged foodborne pathogen. In veterinary medicine, GBS is a well-known mastitis-causing agent in dairy cattle, an important invasive pathogen of warm-water fish species in aquaculture, and an emerging pathogen of dromedary camels. Adaptation to new hosts and ecological niches of several bacterial pathogens has been linked with the acquisition of various types of mobile genetic elements (MGE), dynamic molecular parasites that can be transferred between bacterial cells, which together from the ‘mobilome’. In GBS, certain MGE have been associated with host-adaptation, with high pathogenicity (e.g. bacteriophages and insertion sequences) and with remodelling of population structure due to positive selection (e.g. integrative conjugative elements, ICE, for tetracycline resistance); however, most studies to date primarily focused on human GBS.

The overarching aim of this work was to assess the role of the mobilome in host-adaptation and evolution of GBS with extensive comparative genomic analyses across host groups. This was carried out through specific objectives: i) Fill knowledge gaps with regards to presence and distribution of various classes and types of MGE among GBS lineages and host groups. An implementation and evaluation of existing methods for the detection of MGE in GBS was carried out to facilitate subsequent analyses, and a new typing and detection method for GBS prophages and phage-inducible chromosomal islands (PICI) was developed. Findings show a high diversity of prophage types and of their relative insertion sites, as well as of ICE. One PICI type appears to be ubiquitous in GBS, but PICI as a class show low diversity in GBS compared to other bacterial species, except for GBS from camels. Overall, few known plas mids were detected among GBS isolates of human origin, but thanks to long-read sequencing, novel plasmids with homologs in other streptococci were identified, one of which was highly prevalent among bovine GBS. ii) Improving our understanding of the GBS population structure both at the national (bovine GBS in Sweden, camel GBS in Kenya) and global levels, and the genetic background associated with host-specialist and host-generalist lineages, through analysis of core and accessory genome content. Results support the possibility of reverse zoonotic transmission, with introduction of new lineages of human origin in dairy cattle and subsequent adaptation to the bovine niche thanks to the acquisition of relevant MGE. A high genome plasticity of host-generalists was detected, suggesting these lineages might have a superior ability to uptake and retain foreign DNA compared to host-specialists, from which they differ considerably in terms of recombinogenic potential. Host-specialists and generalists seem to largely evolve independently of each other. iii) Investigate the association of accessory genes and MGE, which could be exerting an impact in host-adaptation, with the major GBS host groups (humans, bovines, fishes and camels) through large-scale genome-wide association studies (GWAS). Findings indicate that a limited number of genomic islands (GEI), some of which are recognised MGE, are associated with each host group: scpB-lmb transposon in humans, Lac.2 in cattle, locus 3 in fishes and two major GEI in camels. The distribution of the former three elements among host-specialist and hostgeneralist lineages within GBS, and among other streptococci that affect the same hosts, suggests they are potentially major drivers of host-adaptation in GBS and in streptococci more widely. The presence vs absence of these host-associated genetic markers demarcates separate ‘ecotypes’, i.e. groups of bacterial species and strains that are well adapted to a certain ecological niche.

Overall, this work shows that the pangenome cannot be understood without a focus on all affected host species, that the GBS mobilome comprises many types of MGE, and that a select group of MGE may drive host-adaptation both within and beyond GBS.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
• Supervisor's Name: Forde, Dr. Taya and Zadoks, Prof. Ruth
• Date of Award: 2021
• Depositing User: Theses Team
• Unique ID: glathesis:2021-82599
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 17 Dec 2021 10:38
• Last Modified: 03 Feb 2025 16:40
• Thesis DOI: 10.5525/gla.thesis.82599
• URI: https://theses.gla.ac.uk/id/eprint/82599

Related URLs

• Article DOI
• Article DOI
• Article DOI
• Article DOI