Doctoral Dissertations
Date of Award
12-2023
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Major
Comparative and Experimental Medicine
Major Professor
Dr. Mohamed Abouelkhair
Committee Members
Dr. Stephen Kania - Dr. Oudessa Kerro Dego - Dr. Raghavendra Amachawadi
Abstract
S. pseudintermedius, a pathogen affecting canines, has displayed a troubling surge in resistance to methicillin and multiple drugs, posing a challenge in veterinary care. Its ability to colonize humans and cause severe illnesses, especially in vulnerable individuals, highlights its zoonotic potential. The rise of methicillin-resistant S. pseudintermedius (MRSP) raises significant public health concerns. Thus, comprehending the genetic diversity and molecular epidemiology of different S. pseudintermedius strains from humans and canines could aid in developing effective vaccines. A recent approach involves a multivalent vaccine targeting canine infections, utilizing attenuated recombinant proteins to boost immunity and counter the virulence factors, offering potential protection for companion animals. To tackle the rising number of human infections, it is critical to discover key virulence factors found in S. pseudintermedius strains from human hosts as well. The objective of this study was twofold: (a) to examine the molecular epidemiology and antimicrobial resistance patterns of multiple S. pseudintermedius isolates obtained from dogs across different regions in the United States and (b) to assess the distribution of antimicrobial resistance and virulence factor genes in S. pseudintermedius isolates from both human and canine hosts using Pan-genomic analysis. In this study, the whole genomes of eleven S. pseudintermedius isolates from infected dogs, submitted to veterinary diagnostic laboratories in the United States, vi were sequenced using MiniSeq Illumina. Through a comprehensive pan-genomic analysis of all available S. pseudintermedius isolates from both canine and human origins in the GenBank database, six crucial virulence factor genes (srtA, Sbi, AdsA, SpmerA, LukF-I and LukS-I) were consistently identified across all S. pseudintermedius isolates. These identified virulence factors present promising candidates for the development of a vaccine for human use, considering the significant rise in S. pseudintermedius incidence in human populations, which remains a critical concern. Alongside these findings, numerous and highly conserved hypothetical proteins were detected, warranting further investigation. This study represents the first comprehensive investigation into the molecular epidemiology, antimicrobial resistance, and virulence factor genes of all reported isolates of S. pseudintermedius from both canine and human hosts. Its primary focus is on the identification of potential genes that could serve as vaccine candidates.
Recommended Citation
Roozitalab, Ashkan, "The Genomic Landscape of Staphylococcus pseudintermedius: Exploring Genome Diversity, Phylogeny, Vaccine Candidates. " PhD diss., University of Tennessee, 2023.
https://trace.tennessee.edu/utk_graddiss/11671