Date of Award
12-3-2024
Document Type
Thesis
School
School of Chemical & Biotechnology
Programme
Ph.D.-Doctoral of Philosophy
First Advisor
Dr.P.Nithyanand
Keywords
Biofilm, Orthopedic Implant Infection, Quorum Sensing, Metal Complex, Virulence
Abstract
Orthopedic implants are medical devices employed to repair the damaged structure and function of an injured musculoskeletal system. It helps millions of people suffering from bone fractures and arthroplasty. The increased use of orthopedic implants has given rise to implant-associated biofilm infections. Biofilm-mediated Implant-associated osteomyelitis (IAO) is a major concern in the medical field, wherein the treatment involves debridement, administration of antibiotics and removal of implants leading to increased cost of treatment.
The keystone bacterial pathogens involved in orthopedic implant-associated infections are Staphylococcus aureus and Acinetobacter baumannii which are members of the ESKAPE pathogens. A. baumannii has gained resistance against almost all antibiotics and have become a keystone pathogen in the clinical sector. S. aureus is a notorious pathogen responsible for chronic implant-associated osteomyelitis which is found to be highly resistant to various drugs compared to S. aureus isolated from non-implant sites. To overcome antibiotic resistance and biofilms, a novel anti-virulent treatment measure for implant-mediated bone infection is the need of the hour. Attenuating biofilms and virulence factors is an effective approach to control chronic implant infections.
Therefore, in the current study, we focused on targeting the virulence and biofilms of A. baumannii and Methicillin-resistant Staphylococcus aureus using palladium(II) complex of NNN chelating thiazolinyl-picolinamide. Among different Pd(II) complexes, Pd(II)-E had potent biofilm inhibitory effects for both A. baumannii and MRSA. In addition, Pd(II)-E effectively mitigated quorum sensing mediated virulence factors of A. baumannii including pili motility and polysaccharide production. Pd(II)-E acts as a potent anti-virulent agent against MRSA by inhibiting slime synthesis, spreading motility, and staphyloxanthin pigment production. qPCR analysis further confirmed the downregulation of genes responsible for biofilms and virulence in both pathogens.
Since Pd(II)-E suppressed virulence and biofilms of keystone pathogens involved in orthopedic implant infections, Pd(II)-E was coated on titanium plates in view of fabricating anti-infective orthopedic implants. The efficacy of coated titanium plates in preventing dual-species biofilm infections was assessed. Pd(II)-E coated titanium plates showed remarkable alleviation against mono- and dual-species biofilms of MRSA and A. baumannii. The study also found that host protein binding factors of pathogens have a vital role in dual-species biofilm infections. The stability of the coated plates in artificial synovial fluid (ASF) was confirmed using EDAX analysis.
qPCR studies were performed between mono- and dual-species biofilms to identify interaction between dual-species biofilms. The effectiveness of Pd(II)-E coated plates was investigated at the molecular level using qPCR analysis for genes responsible for biofilms, quorum sensing, and host protein binding factors. The results revealed that Pd(II)-E coated plates downregulated the genes of the above-mentioned virulence of mono- and dual-species biofilms in ASF. Biocompatibility of the coated titanium plate was confirmed in human osteoblast cells. Taken together, we envision that Pd(II)-E coated titanium may act as a potent bioactive biomaterial to prevent orthopedic implant infection.
Recommended Citation
J, Sowndarya Ms, "Preventing Orthopedic Implant Associated Biofilm Infections Using Transition Metal Complex Laminated Bioactive Implants" (2024). Theses and Dissertations. 111.
https://knowledgeconnect.sastra.edu/theses/111