AUTHOR=Varghese Brian R. , Goh Kelvin G. K. , Desai Devika , Acharya Dhruba , Chee Collin , Sullivan Matthew J. , Ulett Glen C. 

TITLE=Variable resistance to zinc intoxication among Streptococcus agalactiae reveals a novel IS1381 insertion element within the zinc efflux transporter gene czcD

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1174695

DOI=10.3389/fimmu.2023.1174695

ISSN=1664-3224

ABSTRACT=<p><italic>Streptococcus agalactiae</italic>, also known as group B Streptococcus, is an important human and animal pathogen. Zinc (Zn) is an essential trace element for normal bacterial physiology but intoxicates bacteria at high concentrations. Molecular systems for Zn detoxification exist in <italic>S. agalactiae</italic>, however the degree to which Zn detoxification may vary among different <italic>S. agalactiae</italic> isolates is not clear. We measured resistance to Zn intoxication in a diverse collection of clinical isolates of <italic>S. agalactiae</italic> by comparing the growth of the bacteria in defined conditions of Zn stress. We found significant differences in the ability of different <italic>S. agalactiae</italic> isolates to resist Zn intoxication; some strains such as <italic>S. agalactiae</italic> 18RS21 were able to survive and grow at 3.8-fold higher levels of Zn stress compared to other reference strains such as BM110 (6.4mM vs 1.68mM Zn as inhibitory, respectively). We performed <italic>in silico</italic> analysis of the available genomes of the <italic>S. agalactiae</italic> isolates used in this study to examine the sequence of <italic>czcD</italic>, which encodes an efflux protein for Zn that supports resistance in <italic>S. agalactiae</italic>. Interestingly, this revealed the presence of a mobile insertion sequence (IS) element, termed <italic>IS</italic>1381, in the 5′ region of <italic>czcD</italic> in <italic>S. agalactiae</italic> strain 834, which was hyper-resistant to Zn intoxication. Interrogating a wider collection of <italic>S. agalactiae</italic> genomes revealed identical placement of <italic>IS</italic>1381 in <italic>czcD</italic> in other isolates from the clonal-complex-19 (CC19) 19 lineage. Collectively, these results show a resistance spectrum among <italic>S. agalactiae</italic> isolates enables survival in varying degrees of Zn stress, and this phenotypic variability has implications for understanding bacterial survival in metal stress.</p>