AMOP Antimicrobials against Ocular Pathogens (AMOP)
Millions of people suffer from infectious diseases each year. Unfortunately, morbidity is also in the millions and health care costs soar in the presence of infections that are not susceptible to the available antimicrobials. The unchecked emergence of antimicrobial resistance is a phenomenon that could potentially transport us back to the pre-antibiotic era if proper measures are not taken.
Mortality and morbidity associated with infection by antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and extensively drug-resistant tuberculosis (XDR-TB) is on the rise. In particular, untreatable, multiple drug resistant Gram-negative bacteria poses the greatest threat to public health in the coming decade.
Antibiotic resistance is a world-wide critical healthcare issue. Southeast Asia is particularly at risk for infections as eye infections affect thousands of people annually. The prevalence of fungal infections in the eye and Fusarium is particularly significant as primary culprits, but even Tuberculosis (TB) and pneumonia are common in developed and emerging countries. Despite these concerns, the antibiotic drug development pipeline is depleted, and many big pharmaceuticals have long opted out of antibiotic discovery and development.
The emergence of the resistance of fungus and yeast to existing drugs is becoming more recognised, because it is exacerbated by the very few drugs available for fungus and yeast. Candiasis and aspergilliosis are becoming common in Europe and fungal infections are a major healthcare issue in Asia. AMOP joins in the effort against infections through our validated ElucidatusTM technology platform and our drug development pipeline of antimicrobial compounds, targeting ophthalmic, resistant Gram-negative infections, as well as Gram positive pathogens, especially MRSA and fungus which are currently underserved segments of clinical need.
Aside from the list of patents filed, AMOP has developed a portfolio of compounds in the area of antimicrobial discovery through the use of a multi-disciplinary platform (Figure 1). The research and development capability of AMOP has been developed through a series of outstanding collaborations with several institutions in Singapore (SNEC, Bioinformatics Institute, Genome Institute of Singapore, National University of Singapore and School of Engineering, Singapore General Hospital, Pathology, Nanyang Technical University), China (South China University of Technology, South China Botantical Garden {State Key Laboratory}), and Switzerland (University of Geneva). AMOP is fortunate to have the support of the Agency for Science, Technology and Research (A*STAR) and SERI in our spin-off quest.
Programme Organisation and Emphasis
AMOP offers educational programmes at all levels from final year projects in undergraduate programmes to PhD and post-graduate level studies. A distinct advantage of working in a multi-disciplinary environment is that the student becomes familiar with all aspects of infections from the chemistry of therapeutics to the clinical stages of antimicrobial development.
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Hanxun Zou, Jun-Jie Koh, Jianguo Li, Shengxiang Qiu, Thet Tun Aung, Rajamani Lakshminarayanan, Xiaoping Dai, Charles Tang, Fang Hui Lim, Lei Zhou, Ai Ling Tan, Chandra Verma, Donald T. H. Tan, Hardy Sze On Chan, Padmanabhan Saraswathi, Derong Cao, Shouping Liu, Roger W. Beuerman, Design and Synthesis of Amphiphilic Xanthone Based Membrane Targeting Antimicrobials with Improved Membrane Selectivity, J Med Chem, 2013; 56(6): 2359-73.
Bai Y, Liu S, Li J, Lakshminarayanan R, Pasmanabhan S, Tang C, Ho D, Verma C, Beuerman RW, Pervushin K. Progressive structuring of a branched antimicrobial peptide on the path to the inner membrane target. J Biol Chem. 2012 Jun 14.
Koh JJ, Qiu S, Zou H, Lakshminarayanan R, Li J, Zhou X, Tang C, Saraswathi P, Verma C, Tan DT, Tan AL, Liu S, Beuerman RW. Rapid bactericidal action of alpha-mangostin against MRSA as an outcome of membrane targeting. Biochim Biophys Acta. 2012 Sep 13 .
Tan XW, Lakshminarayanan R, Liu SP, Goh E, Tan D, Beuerman RW, Mehta JS. Dual functionalization of titanium with vascular endothelial growth factor and -defensin analog for potential application in keratoprosthesis J Biomed Mater Res B Appl Biomater 2012 Nov Epub 2012 Jul 23.
Li J, Lakshminarayanan R, Bai Y, Liu S, Zhou L, Pervushin K, Verma C, Beuerman RW. Molecular dynamics simulations of a new branched antimicrobial peptide: A comparison of force fields. J Chem Phys. 2012 Dec 7;137(21):215101
Bai Y, Liu S, Jiang P, Zhou L, Li J, Tang C, Verma C, Mu Y, Beuerman RW, Pervushin K. Structure-dependent charge density as a determinant of antimicrobial activity of peptide analogues of defensin. Biochemistry. 2009 Aug 4;48(30):7229-39.
Liu S, Zhou L, Chen L, Dastidar SG, Verma C, Li J, Tan D, Beuerman R. Effect of structural parameters of peptides on dimer formation and highly oxidizedside products in the oxidation of thiols of linear analogues of human betadefensin 3 by DMSO. J Pept Sci. 2009 Feb;15(2):95-106.
Liu S, Zhou L, Li J, Suresh A, Verma C, Foo YH, Yap EP, Tan DT, Beuerman RW. Linear analogues of human beta-defensin 3: concepts for design of antimicrobial peptides with reduced cytotoxicity to mammalian cells. Chembiochem. 2008 Apr 14;9(6):964-73.
Seebah S, Suresh A, Zhuo S, Choong YH, Chua H, Chuon D, Beuerman R, Verma C. Defensins knowledgebase: a manually curated database and information source focused on the defensins family of antimicrobial peptides. Nucleic Acids Res. 2007 Jan;35(Database issue):D265-8. Epub 2006 Nov 7. database has had over a million hits.
Head
Assoc Prof Rajamani Lakshminarayanan
Key Personnels
Dr Chandra Verma, PhD, Bioinformatics Institute, Singapore
Dr Jianguo Li, PhD, SERI
Collaborators
Adj Prof Donald Tan, MD, SNEC
Assoc Prof Konstatin Pervushin, Biological Sciences, NTU
Assoc Prof Jodhbir Mehta, MD, SERI/SNEC
Dr Swaine Chen, MD, PhD, Singapore NRF Fellow, GIS, Infectious Diseases, NUS, School of Medicine
Dr Tan Ai Ling, MD, Pathology, SGH
Prof Howard Reizman, PhD, Department of Microbiology, University of Genva
Prof Thomas Dick, PhD, Department of Microbiology, NUS
Prof Seeram Ramakrishna, FREng, VP-Research Strategy, NUS, Mechanical Engineering
Prof Cao Derong , PhD, Department of Chemistry, South China University of Technology
Adj Assoc Prof Timothy Barkham, TTSH, Laboratory Medicine
Dr Josh Granek, PhD, Director Lab of Microbial Genomics, Duke Univeristy
Dr Takashi Suzuki, Visiting Clinician/Scientist, Eihme Graduate School of Medicine, Japan
Research Fellows
Dr Thet Tun Aung, MBBS, MS
Dr Chetna Dhand, PhD
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