Profile
The global bacterial pathogen, Streptococcus pneumoniae colonizes the upper respiratory tract of healthy children and adults. Despite being a natural colonizer, pneumococci causes life-threatening diseases such as pneumonia, septicemia and meningitis killing over a million people worldwide and is classified as priority pathogen by the WHO since 2017. Antibiotic misuse and horizontal gene transfer have resulted in the alarming spread of drug resistant clones globally. Currently available polysaccharide and conjugate vaccines offer limited protection against 13-20 out of 100 known serotypes and are gradually replaced by non-vaccine serotypes. The major goal of my laboratory is to understand the molecular mechanisms of pneumococcal infections and develop novel therapeutics targeting bacterial virulence factors as opposed to conventional antibiotics that are prone to resistance. We use a combination of cellular, biochemical, genetic and multiomics approaches in the lab to address our research objectives.
Current Focus Areas
1. Investigating the pathophysiological significance of host-derived extracellular vesicles during pneumococcal infections.
2. Targeting antimicrobial resistance by screening and identifying drugs targeting bacterial multiple virulence factors.
Selected Publications
1. Saba Parveen, Chinmayi V Bhat, Shaheena Aziz, J Arya, Asmita Dutta, Somit Dutta, Sautan Show, Kuldeep Sharma, John Bernet Johnson, Upendra Nongthomba, Anirban Banerjee, Karthik Subramanian. Bacterial pore-forming toxin pneumolysin drives pathogenicity through shed toxin-loaded host extracellular vesicles. bioRxiv 2023.10.12.561978; doi: 10.1101/2023.10.12.561978. (under revision in iScience) (*Corresponding author)
2. Saba Parveen and Karthik Subramanian*. Emerging Roles of Extracellular Vesicles in Pneumococcal Infections: Immunomodulators to Potential Novel Vaccine Candidates. Front Cell Infect Microbiol. 2022 Feb 14;12:836070. doi: 10.3389/fcimb.2022.836070. (*Corresponding author)
3. Karthik Subramanian, Federico Iovino, Vasiliki Tsikourkitoudi, Padryk Merkl, Sultan Ahmed, Samuel Berry, Marie-Stephanie Achtgen, Mattias Svensson, Peter Bergman, Georgios Sotiriou, Birgitta Henriques Normark. Mannose receptor-derived peptides neutralize toxins and reduce inflammation and pneumococcal disease. EMBO Mol Med. 2020 Nov 6;12(11):e12695. (Top 25% of all research outputs scored by Altmetric)
4. Subramanian K, Henriques-Normark B, Normark S. Emerging concepts in the pathogenesis of Streptococcus pneumoniae: From nasopharyngeal colonizer to intracellular pathogen. Cell Microbiol. 2019 Nov;21(11):e13077 (Top Downloaded Paper, Wiley, 2018-2019)
5. Subramanian K, Neill DR, Malak HA, Spelmink L, Khandaker S, Dalla Libera Marchiori G, Dearing E, Kirby A, Yang M, Achour A, Nilvebrant J, Nygren P, Plant L, Kadioglu A, Henriques-Normark B. Pneumolysin binds to the mannose receptor C type 1 (MRC-1) leading to anti-inflammatory responses and enhanced pneumococcal survival. Nat Microbiol. 2019 Jan;4(1):62-70. (Rated exceptional article in F1000 prime and top 5% in Altmetric in Nature)