Examining the Viability of Antibiotic-Resistant Isolates of Streptococcus pneumoniae to Functionalized Nanoparticles

Date of Award

Spring 2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

First Advisor

Vida A. Dennis

Second Advisor

Mamie T. Coats

Third Advisor

Shree R. Singh

Abstract

Streptococcus pneumoniae causes approximately half a million deaths annually in children under the age of 5 years old worldwide, despite of available vaccines and antibiotics. Antibiotic-resistant strains of pneumococci are emerging due to the overuse of antibiotics. Many strains are resistant against β-lactams and macrolides. Therefore, causing a dissemination of several resistant clones that could undergo serotype replacement, capsular switching, and horizontal transmission of antibiotic resistance genes that are very difficult to control. Henceforth, pneumococcal biofilms are also highly resistant to antimicrobial agents. Biofilms have been detected on mucosal surfaces during pneumonia and middle ear infections. The development of a novel antimicrobial drug is needed to conquer existing mutating S. pneumoniae isolates. Our goal was to investigate the usefulness of penicillin conjugated gold nanoparticles (AuNP-Pen), penicillin encapsulated poly lactic-co-glycolic (PLGA-Pen) and clindamycin encapsulated poly lactic-co-glycolic (PLGA-Clin) nanoparticles as potential multivalent antimicrobials inhibiting the growth of resistant S. pneumoniae. In addition, we also examined the antimicrobial effect of zinc oxide nanoparticles (ZnO NPs) and copper nanoparticles (Cu NPs). The AuNP-Pen produced were 5-10nm spherical particles with 1.06 x 10-6 mol of penicillin/nanoparticle. While the encapsulated PLGA-Pen particles were considerably larger at 10-20nm. Following exposure to the nanoparticles, planktonic pneumococci showed reduced viability in the presence of the 0.125µg/ml AuNP-Pen and 0.25µg/ml PLGA-Pen when compared to AuNP and PLGA in liquid media. However, when examining pneumococcal biofilms independent of the level of penicillin susceptibility, there was a significant difference with a P ≤ 0.001; the inhibitory ability of AuNP compared to that of control against non-adherent cells. Furthermore, while there was a trend for the isolates to survive less well in AuNP and AuNP-Pen compared to PLGA, PLGA-Pen, and PLGA-Clin. The conjugation of penicillin to AuNPs increased biocidal activity compared to the nanoparticle alone and had varying effects on bacteria which correlated with the level of bacterial susceptibility. On the other hand, PLGA and penicillin did not have an enhanced combinatory antibacterial effect on S. pneumoniae . The studies described herein identify the potential for treating antibiotic-resistant pneumococcal infections with known antibiotic-nanoparticle therapeutics.

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