Characterising the Antimicrobial Effect of Zinc Intoxication in Group B Streptococcus

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Sullivan, Matthew J

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Ulett, Glen C

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2023-01-18
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Abstract

Group B Streptococcus (GBS) is a Gram-positive bacteria known for causing a wide range of illnesses in neonates, pregnant woman, elderly, and immunocompromised people. Intrapartum antibiotic prophylaxis is the current prevention measure for pregnant women used worldwide and has been highly successful thus far. However, it is a dangerous long-term approach with the rising antimicrobial resistance crisis. Vaccine development has been ongoing for several decades and remains a key area of study for GBS researchers worldwide. Finding an effective vaccine target candidate that can be packaged in a safe and inexpensive manner is a continuous challenge. The use of metal ions, such as zinc, as an antibacterial has dated back centuries. Its potential to be harnessed against GBS shows promise as an alternative treatment and prevention option, leading to recent characterisation of GBS zinc efflux machinery. It has been established that GBS employs robust strategies to overcome zinc stress and mediate survival. While bacteria require essential nutrient metals for survival, it is presented with nutritional challenges imposed by the vertebrate host during infection. One such strategy is intoxication of invading bacterial pathogens with transition metals. This work assessed 16 strains of GBS from diverse capsular serotypes, sequence types and isolation sources for susceptibility or resistance toward zinc intoxication. The findings show that strains of a variety of clinical backgrounds, capsular types and sequence-types differ in their resistance phenotypes toward zinc intoxication. For example, cpsV and ST-19 were found to be highly resistant to zinc stress, whereas cpsIII and ST-7 and ST-17 were most sensitive to metal intoxication. It is also first reported here that IS1381, a previously identified transposon, has been found in the main zinc export gene, czcD, of strain 834. Investigation of its possible involvement in strain 834’s increased resistance phenotype was inconclusive.

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Thesis (Masters)

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Master of Medical Research (MMedRes)

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School of Pharmacy & Med Sci

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The author owns the copyright in this thesis, unless stated otherwise.

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Subject

Group B Streptococcus

antimicrobials

zinc

intoxication

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