Novel strategies for the control of Streptococcus agalactiae (Group B Streptococcus) in aquaculture

Krajangwong, Sakranmanee (2019) Novel strategies for the control of Streptococcus agalactiae (Group B Streptococcus) in aquaculture. PhD thesis, University of Glasgow.

Abstract

Streptococcus agalactiae (Group B Streptococcus, GBS) has a wide host range that includes aquatic animals. GBS are commensal bacteria of intestinal and genitourinary tracts in humans and animals but some lineages are adapted to specific hosts and have become hypervirulent clones, e.g. clonal complex (CC)17 is the main cause of neonatal invasive GBS infection. CC17 is transferred from the maternal vaginal tract to the neonate during birth, and neonatal GBS has been a major focus of scientific study. However, since the end of the 20th century, GBS sequence type (ST)283 infection has caused a quiet epidemic in Southeast Asia. It was confirmed as a zoonotic disease in 2015 and consumption of raw fish was the major route of transmission to nonpregnant humans whom did not have comorbidities. Common clinical manifestations were meningitis, endocarditis and septic arthritis and mortality rate was 3.4%. Control of GBS disease in humans, fishes and cattle currently relies primarily on use of antimicrobials. To reduce the burden of human GBS disease, economic losses resulting from GB infections in aquaculture and the threat of rising antibiotic resistance, this project’s main aims were to find bacteriocins active against GBS and to explore host-adaptation through metabolic profiling to develop alternative control strategies against this bacterium.

One hundred and twelve S. agalactiae isolates (19 human, 36 bovine and 57 piscine) were tested for bacteriocin production ability in antagonism assays. A class III bacteriocin, produced by ST17 human isolate, was identified and designated “agalacticin A”. Its spectrum was determined on solid medium assay. Agalacticin A showed killing activity against human, bovine and piscine GBS strains supporting its potential as GBS-specific antimicrobial agent and it had a narrow spectrum towards other pyogenic Streptococcus species, Streptococcus dysgalactiae subsp. dysgalactiae and Streptococcus canis. Vancomycin-resistant Enterococcus faecalis could also be inhibited by agalacticin A at high concentration but there was no impact on Lactobacillus species, which are important in the human vaginal microbiome. Pre-screening of agalacticin A in a Galleria mellonella (the greater wax moth) challenge model showed its bacteriolytic effect and its usefulness for treatment of GBS-challenged wax moth larvae. However, the duration of agalacticin A action is limited to 6 hrs due to elimination by an insect excretory system, which suggests agalacticin A is likely to be removed by the glomerular filtration in vertebrates.

In an attempt to find vaccine candidates or metabolic manipulations to control GBS in aquaculture, investigation was conducted into metabolic pathways associated with GBS from particular hosts and potential mechanisms of competitive advantage or niche restriction. Biolog GEN III was used to identify phenotypic markers of niche adaptation using metabolic profiling. Eighty-eight isolates (29 bovine, 17 human and 42 piscine) were tested for their use of sugars, sugar alcohol, hexose-phosphate, amino acids, hexose acids and carboxylic acids, esters and fatty acids. Fish-specifc phenotypes were not identified across all CCs associated with aquaculture. Instead, CC-associated phenotypes were described. Loss of catabolism of D-salicin and other β-glucosides (β-methyl-Dglucoside) was observed in CC283 and CC17. Further preliminary study on salicin (sal) utilization and hyaluronidase (hyl) production by GBS from different CC showed that the sal- /hyl+ phenotype is associated with the only known hypervirulent GBS clades in humans, i.e. CC283 and CC17. Mechanisms underlying the lack of salicin hydrolysis and its association with virulence are unknown. Several potential pathways are described, leading to suggestions for further research.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: Walker, Prof. Daniel and Ruth, Prof. Zadoks
• Date of Award: 2019
• Depositing User: Miss Sakranmanee Krajangwong
• Unique ID: glathesis:2019-74347
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 06 Sep 2019 11:28
• Last Modified: 17 Jan 2025 15:26
• Thesis DOI: 10.5525/gla.thesis.74347
• URI: https://theses.gla.ac.uk/id/eprint/74347