Manjulatha Sara

Research Title: Development of Biologically Active Biomaterials Against Bacterial Colonisation 

Supervisor: Professor Mark Willcox

Co-supervisors: Dr Alex Hui, Dr Edgar Wong and Dr Mohammad Yasir

Research

Background:  Contact lens wear increases the risk of microbial keratitis (MK). To control various strategies followed, including cationic peptide, Mel4 immobilised lenses showed  65% reduced corneal infiltrates but lost antimicrobial activity over time due to proteolysis. Peptoids are oligomers based on a poly-glycine backbone with an amide side chain that mimics the parent molecule, retains activity, resistant to proteases, and non-toxic.

Thesis aim: Development of biologically active biomaterials against bacterial colonisation in vitro and in vivo models.

Methods: Minimum inhibitory concentration (MIC) and maximum bactericidal concentration (MBC) were determined following the micro broth dilution method according to Clinical Laboratory Systematic Investigation (CLSI) guidelines. Lead peptidomimetics resistance to protease was assessed using exo and endogenous proteases.  The toxicity of compounds was determined against mammalian erythrocytes and corneal epithelial cells. Antimicrobial lens adhesion assay performed against resistant and sensitive strains of ocular infection isolates. Peptidomimetic immobilised lens characterisation studies include surface hydrophobicity, XPS, and zeta potential. Explored the mechanism of action of candidate-bound lenses with bacterial membranes.  Further studies include novel antimicrobial lens activity in an animal model to reduce the incidence or severity of ocular infection.

Results: TM 5, TM 18, and 1083 showed good antimicrobial activity with increased hemolytic profile at higher concentrations. Peptoid mimics incubated with trypsin for 24 hours showed no difference in the bacterial MIC with trypsin and proteinase K and without trypsin, indicating resistance to protease digestion. Hemolytic activity of 12 compounds was performed, out of which three compounds showed lower toxicity and thus a greater therapeutic index. Peptoid base mimics TM 5, TM 14, TM 18, and 1083 immobilised to etafilcon lens surfaces showed more than 2-5 log reduction in P. aeruginosa and S. aureus of different structural compounds.

Expected outcome: Peptoid immobilised contact lenses will have excellent antimicrobial activity, and resist hydrolysis, and fouling. That reduces the incidence or severity of ocular infection.

Biography

Understanding of health and infections at molecular and cellular levels, including antimicrobial drug activity, bioengineering of biomaterials, biofilm inhibition and mechanisms of action of biofilms at a cellular level, interaction at the molecular level, and gene-related resistance mechanisms. They drive innovation in diagnostics. Treatment and prevention strategies that contribute significantly to medical advances and improved patient care.

Education

Master’s in science from Annamalai University, Chidambaram, India.  

Awards

Scientia Scholarship from the University of New South Wales, Sydney, Australia, to study towards a PhD.  2020

Received International travel grant from Association for Research in Vision and Ophthalmology 2021

Received travel grant from International Society for Contact Lens Research to attend their conference in Portugal in 2022

Conference Attendance

Lorne infection and Immunity 2021:  The Title is “Synergistic activity of ciprofloxacin and azithromycin against staphylococci and streptococci”

ARVO 2021 - The title is “Synergistic activity of a peptide mimic with quinolones and cephalosporins against Staphylococcus aureus”

Australian Society for Microbiology 2021: “Identification and diagnosis of Pythium insidiosum infections”

International Society for Contact Lens and Research. “Development of New antimicrobial contact lenses”. Sept 2022

Peptoids Summit “Antimicrobial activity of peptoids against clinical pathogens.” Sept 2022

International Cornea Contact Lens Congress. “Production of new antimicrobial contact lenses” Oct 2022

Asian Network of Natural & unnatural Materials (ANNUM-10) – “The efficacy of various attachment strategies to produce covalently bound antimicrobial contact lenses” – 1^st Feb 2023

American Society of Microbiology (ASM)  – ” The effect of peptoids covalently immobilised on etafilcon A contact lenses against bacteria” 15^th -19^th June 2023

Australian Society of Microbiology (ASM) – “The ability of covalently bound peptoids to reduce adhesion of Pseudomonas aeruginosa to contact lenses” – 3^rd-6^th July 2023

International Meeting on Antimicrobial Peptides (IMAP) - “Peptoid-bound silicone lens ability to reduce adhesion of P aeruginosa” – 6-8^th Sep 2023

Affilations and Memberships

Association for Research in Vision and Ophthalmology

American Society of Microbiology

Australian Society of Microbiology