Characterization of Streptococcus mitis subsp. carlssonii isolated from human vagina: prevalence, phenotypic, and genomic insights

Jake Adolf V. Montecillo^1,2,3Heon Jong Yoo⁴Yoo-Young Lee⁵Chul Min Park⁶Angela Cho⁶Hyunsu Lee⁷Jong Mi Kim^8,9Nan Young Lee¹⁰SunHyun Park¹¹Nora Jee-Young Park^12,8Hyung Soo Han^13,3,8Gun Oh Chong^8,9*Incheol Seo^14,3,8*

• ¹Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea, Deagu, Republic of Korea
• ²Clinical Omics Institute, Kyungpook National University, Daegu 41405, Republic of Korea, Daegu City, Republic of Korea
• ³Brain Korea 21 FOUR Program, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea, Daegu City, Republic of Korea
• ⁴Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea, Daejeon, Republic of Korea
• ⁵Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea, Seoul, Republic of Korea
• ⁶Department of Obstetrics and Gynecology, Jeju National University Hospital, Jeju National University College of Medicine, Jeju 35015, Republic of Korea, Jeju, Republic of Korea
• ⁷Department of Physiology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea, Yangsan, Republic of Korea
• ⁸Clinical Omics Institute, Kyungpook National University, Daegu 41405, Republic of Korea, Daegu, Republic of Korea
• ⁹Department of Obstetrics and Gynecology, Kyungpook National University Chilgok Hospital, Daegu 41404, Republic of Korea, Daegu, Republic of Korea
• ¹⁰Department of Clinical Pathology, School of Medicine, Kyungpook National University, Daegu 41405, Republic of Korea, Daegu, Republic of Korea
• ¹¹Division of Advanced Predictive Research, Center for Bio-Signal Research, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea, Daejeon, Republic of Korea
• ¹²Department of Pathology, Kyungpook National University Chilgok Hospital, Daegu 41404, Republic of Korea, Daegu, Republic of Korea
• ¹³Department of Physiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea, Daegu, Republic of Korea
• ¹⁴Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea, Daegu, Republic of Korea

The genus Streptococcus is a heterogenous group of commensal and pathogenic bacteria. Members of this genus are classified into two major groups, the pyogenic group and the viridans group streptococci (VGS). VGS are frequently found as normal members of the human microbiome and are regarded as commensals. In this work, we characterized a VGS strain isolated from the vaginal swab sample of a Korean patient diagnosed with endometrial cancer. Phylogenetic, phenotypic, and genome-based analyses confirmed the classification of the strain K0074 as a member of the S. mitis complex. Based on the phylogenetic analyses, the species belonged to the recently established Streptococcus mitis subsp. carlssonii. The strain was found to be rare in the vaginal microbiome, but prevalent in the oral and nasal microbiome samples. K0074 neither triggered an inflammatory response nor caused cytolytic and cytotoxic effects on human cervical cancer cell line. Genome analysis uncovered the genetic basis of the strain's metabolism, virulence factors, and potential antimicrobial resistance phenotypes. Moreover, comparative genomics of the strain and closely related species and subspecies highlighted their striking differences in gene properties and biological functions. Overall, the new strain exhibited low virulence and pathogenic potentials and thus, is regarded as a commensal member of the human microflora. The genetic divergence of K0074 from closely related strains offers a compelling foundation for future investigations into the strain's potential functional specialization and its adaptation within the vaginal microbiome.