Role of Staphylococcal Pathogenicity Island (SaPI) in adaptation and virulence of Staphylococcus aureus

Staphylococcus aureus (S. aureus) is a pathogenic bacterium that can infect any organ of the human body. It’s one of the most successful pathogens, having remarkable adaptability and virulence. S. aureus strains can carry different mobile genetic elements (MGEs), including plasmids, transposons, staphylococcus cassette chromosomes (SCC), bacteriophages and staphylococcal pathogenicity islands (SaPIs), which contribute to their virulence, broad host range and antibiotic resistance. Horizontal transfer of MGEs among different S. aureus strains plays a vital role in the evolution of this pathogen.

SaPIs are highly mobile chromosomal islands that are induced to excise and replicate by specific phages, “helper phages”. The SaPI replicated DNA is packaged in phage-encoded particles and released upon phage-mediated lysis. These islands, often carry unique toxin genes, move readily between strains, mediate transfer of unlinked chromosomal genes and interfere with the reproduction of the very phages they parasitize. All sequenced genomes of naturally occurring staphylococcal strains contain at least one intact or defective SaPI.

I propose that the diversity, adaptability and virulence of this notorious pathogen depend greatly on its extraordinary islands (SaPIs). The focus of my research proposal is these incredible islands. An understanding of their biology and capabilities will enable us to modify the SaPI and consequently reduce the severity and spread of staphylococcal infection. The proposed research focuses on SaPI’s complex role in HGT, in staphylococcal genomic plasticity and in the metamorphosis of this infamous pathogen.

• Wellcome Trust/DBT India Alliance Intermediate Fellowship (2017)
• Vilcek Fellowship (Vilcek Fellowship Endowment Fund for NYU) (2014)
• Bill and Melinda Gates Foundation Global Health Travel Award to attend the Keystone Symposia B3 Tuberculosis: Biology, Pathology and Therapy (2009)
• Senior Research Fellowship (SRF), Council of Scientific and Industrial Research (CSIR) (2005)
• JOINT CSIR-UGC TEST (NET) for Junior Research Fellowship and Eligibility for Lectureship (2003) 

• Novick RP, Ram G. (2017). Staphylococcal pathogenicity islands movers and shakers in the genomic firmament. Curr. Opin. Microbiol. 38:204.

• Martínez-Rubio R, Quiles-Puchalt N, Martí M, Humphrey S, Ram G, Smyth D, Chen J, Novick RP, PenadEs JR (2016). Phage-inducible islands in the Gram-positive cocci. The ISME Journal 11:1042.

• Novick RP, Ram G. (2016). The floating (pathogenicity) island: a fascinating, if unsavory, genomic dessert. Trends in Genetics 32:126.

• Ram G, Chen J,  Ross  HF,  Novick RP (2015). An insight into staphylococcal pathogenicity island-mediated interference with phage late gene transcription. Bacteriophage 5:e1028608.

• Chen J, Ram G, Yoong P, PenadEs JR, Shopsin B, Novick RP (2015) An rpsL-based allelic exchange vector for Staphylococcus aureus. Plasmid 79:14.

• Chen J, Ram G, Penades JR, Brown S, Novick RP (2015) Pathogenicity Island-Directed Transfer of Unlinked Chromosomal Virulence Genes. Mol Cell. 57(1): 49.

• Chen J, Carpena N, Quiles-Puchalt N, Ram G, Novick RP, Penades JR. (2014) Intra- and inter-generic transfer of pathogenicity island-encoded virulence genes by cos phages. The ISME Journal 9:1263.

• Ram G, Chen J, Ross HF, Novick RP. (2014) Precisely modulated pathogenicity island interference with late phage gene transcription. Proc Natl Acad Sci USA 111:14541.

• Chen J, Yoong P, Ram G, Torres VJ, Novick RP. (2014) Single-copy vectors for integration at the SaPI1 attachment site for Staphylococcus aureus. Plasmid 76:7.

• Quiles-Puchalt N, Martínez-Rubio R, Ram G, Lasa I, Penades JR (2014). Unravelling bacteriophage ϕ11 requirements for packaging and transfer of mobile genetic elements in Staphylococcus aureus. Molecular Microbiology 91:437.

• Ram G, Chen J, Kumar K, Ross  HF, Ubeda C,  Damle PK, Lane KD, Penades JR, Christie GE, Novick RP (2012) SaPI interference with helper phage reproduction is a paradigm of molecular parasitism. Proc Natl Acad Sci USA 109:16305.

• Damle PK, Wall EA, Spilman MS, Dearborn AD, Ram G, Novick RP, Dokland T, Christie GE. (2012) The roles of SaPI1 proteins gp7 (CpmA) and gp6 (CpmB) in capsid size determination and helper phage interference. Virology 432:282.

• Hossain MJ, Korde R, Singh PK, Kanodia S, Ranjan R, Ram G, Kalsey GS, Singh R, Malhotra P. (2010). Plasmodium falciparum Tudor Staphylococcal Nuclease interacting proteins suggests its role in nuclear as well as splicing processes. Gene 468:57.

• Kumar K, Tharad M, Ganapathy S, Ram G, Narayan A, Khan JA, Pratap R, Ghosh A, Samuchiwal SK, Kumar S, Bhalla K, Gupta D, Natarajan K, Singh Y, Ranganathan A. (2009) Phenylalanine-rich peptides potently bind ESAT6, a virulence determinant of Mycobacterium tuberculosis, and concurrently affect the pathogen’s growth. PLoS ONE 4:e7615.

• Rao A, Ram G, Saini AK, Vohra R, Kumar K, Singh Y, Ranganathan A. (2007) Synthesis and Selection of De Novo Proteins That Bind and Impede Cellular Functions of an Essential Mycobacterial Protein. Applied and Environmental Microbiology 73:1331.

• Rao A, Chopra S, Ram G, Gupta A, Ranganathan A. (2005) Application of the “Codon-Shuffling” Method SYNTHESIS AND SELECTION OF DE NOVO PROTEINS AS ANTIBACTERIALS. 2005. The Journal of Biological Chemistry 280:23614.