For a better experience, click the Compatibility Mode icon above to turn off Compatibility Mode, which is only for viewing older websites.

Santosh Katiyar

Santosh Katiyar, PhD

Research Associate Professor


Department: Microbiology & Immunology

Education

  • PhD - Central Drug Research Institute, Lucknow, India (1986)

Dr. Katiyar is a research associate professor in the Department of Microbiology & Immunology at Drexel University College of Medicine.

Research Overview

Dr. Katiyar is interested in the molecular mechanisms of antifungal resistance.

Research Interests

Molecular mechanisms of antifungal resistance

Research

Opportunistic fungal infections have increased dramatically over the last few decades due to the increased number of individuals who are immunocompromised in association with AIDS, organ and tissue transplantation, and long term treatments for cancer patients. In recent years, Candida glabrata has emerged as the second most common cause of mucosal and invasive fungal infection. Most C. glabrata isolates display intrinsically low susceptibility and capacity for acquired resistance to sterol synthesis-inhibiting azoles, the major antifungal group. As in C. albicans, azole resistance is most commonly mediated by upregulated expression of multidrug transporters, a mechanism that is the most important problem facing antimicrobial chemotherapy.

The new class of antifungals are echinocandins (ECs), semisynthetic lipopeptide inhibitors of β-1,-3- glucan synthase and hence fungal cell wall synthesis. ECs are fungicidal especially for Candida albicans and Aspergillus fumigatus; other fungi have variable or poor susceptibility for reasons which are unclear.

Echinocandins (ECs) resistance in Fungi:

ECs (including Caspofungin [Merck], Micafungin [Astellas] and Anidulafungin [Pfizer]) acquired resistance has been documented in few Candida species and will increase as their use expands. In Saccharomyces cerevisiae and related yeast, mutations that confer acquired EC resistance have been mapped to the integral membrane protein Fks1 or its paralog encoding glucan synthase. We focus our studies on EC target, Fks1 using site-directed mutagenesis, and deletion strategy in S. cerevisiae as a model fungi by the development of novel PCR-based methods. Recently,we have identified the Fks1 residue (hot spot 1 region) from Candida parapsilosis, Scedosporium prolificans, S. apiospermum and Fusarium solani and propose that Fks1 sequences represent the primary determinants of intrinsic EC resistance of these fungi. To test the role of Fks1 in intrinsic EC resistance, we have constructed Fks1 hybrids in S. cerevisiae by incorporating Fusarium solani hot spot 1 region of Fks1 residues, the hybrid conferred significantly reduced EC susceptibility further supported our hypothesis.

Candida glabrata is closely related to S. cerevisiae, and encodes Fks1/2/3 orthologs, but their function, regulation and role in reduced ECs susceptibility (RES) is unclear. We have characterized Fks1/2/3 in C. glabrata by gene disruption, expression and site-directed mutagenesis to understand the basis for ECs resistance/susceptibility.

However, the acquired ECs resistance especially by caspofungin is not only limited to the mutations in target gene FKS.  Recently we were the first to report the mutations identified in long chain bases of shingolipid biosynthesis pathway in clinical isolates as well as laboratory generated mutants of Candida glabrata . These studies may enhance the echinocandin therapy and shed light on the mechanism of echinocandin action.

 

Publications

Selected publications
(See all Santosh Katiyar's publications in PubMed.)

"Fks1 and Fks2 are functionally redundant but differentially regulated in Candida glabrata: implications for echinocandin resistance"
Katiyar S, Healey K, Johnson M, and TD Edlind 
Antimicrobial Agents and Chemotherapy, 56 (12): 6304-9, Dec 2012.

"Candida glabrata mutants demonstrating paradoxical reduced caspofungin susceptibility but increased micafungin susceptibility"
Healey KR, Katiyar SK, Castanheira M, Pfaller, MA, and TD Edlind
Antimicrobial Agents and Chemotherapy, 55 (8): 3947-3949, 2011.

"A new Fks hotspot for acquired echinocandin resistance in Saccharomyces cerevisiae and its contribution to intrinsic resistance of Scedosporium species"
Johnson ME, Katiyar SK, and TD Edlind
Antimicrobial Agents and Chemotherapy, 55 (8): 3774-3781, 2011.

"Mutational analysis of flucytosine resistance in Candida glabrata"
Edlind TD and SK Katiyar
Antimicrobial Agents and Chemotherapy, 54: 4733-4738, 2010.

Role for FKS1 in the intrinsic echinocandin resistance of Fusarium solani as evidenced by hybrid expression in Saccharomyces cerevisiae.
Katiyar SK, and TD Edlind.
Antimicrobial Agents and Chemotherapy, 53: 1772-1778, 2009.

"A naturally-occurring Fks1p proline to alanine amino acid change in Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis accounts for reduced echinocandin susceptibility."
Garcia-Effron G, Katiyar SK, Park S, Edlind TD, and DS Perlin.
Antimicrobial Agents and Chemotherapy, 52(7):2305-2312, 2008.

"Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility."
Katiyar SK, Pfaller M, and T Edlind.
Antimicrobial Agents and Chemotherapy, 50(8): 2892-2894, 2006.

"Promoter-dependent disruption of genes: simple, rapid, and specific PCR-based method with application to three different yeast." 
Edlind TD, Henry KW, Vermitsky JP, Raj S, Edlind MP, and SK Katiyar
Current Genetics, 48: 117-125, 2005.

"Candida albicans echinocandin “target” identified by crosslinking is homolog of Pil1 and Lsp1, sphingolipid-dependent regulators of cell wall integrity signaling."
Edlind T, and SK Katiyar. 
Antimicrobial Agents and Chemotherapy, 48: 4491, 2004.

"Antifungal activity in Saccharomyces cerevisiae is modulated by calcium signalling."
Edlind T, Smith L, Henry K, Katiyar SK, and J Nickels. 
Molecular Microbiology, 46, 257-268, 2002.

"Aspergillus fumigatus CYP51 sequence: potential basis for fluconazole resistance."
Edlind TD, Henry KW, Metera K, and SK Katiyar.
Molecular Microbiology, 39(3): 299-302, 2001.

"Identification and expression of multidrug resistance-related ABC transporter genes in Candida krusei."
Katiyar SK, and TD Edlind.
Molecular Microbiology, 39: 109-116, 2000.

"Antagonism of azole activity against Candida albicans following induction of multidrug resistance genes by selected antimicrobial agents." 

Henry KW, Cruz MC, Katiyar SK, and TD Edlind. 
Antimicrobial Agents and Chemotherapy, 43, 1968-1974, 1999.


Contact Information


Research Office

Department of Microbiology & Immunology
2900 W. Queen Lane
Philadelphia, PA 19129
Phone: 215.991.8337
Fax: 215.848.2271