Doctor of Philosophy (PhD)
Department of Biological Sciences
K. pneumoniae is a Gram-negative, capsule forming bacterium. It can live both freely in the environment or in the symbiotic mode on a host. It is responsible for causing hospital acquired infections in immunocompromised patients and can cause community acquired infections in healthy individuals. K. pneumoniae is highly pathogenic and resistant to antibiotics and chemical treatments. Colistin is used as a last resort antibiotic to treat infections related to MDR (multidrug resistant) K. pneumoniae strains. However, K. pneumoniae is now becoming resistant to colistin. In the future, K. pneumoniae poses a major threat because it is evolving into a highly pathogenic and extremely antibiotic resistant superbug. The highly conserved DedA membrane protein superfamily is known to be required for antibiotic resistance and other functions in several bacterial species. I found a virulent K. pneumoniae ST258 strain with a mutation in dkcA (dedA of Klebsiella required for colistin resistance) displayed increased sensitivity to colistin due to a reduction in critical lipopolysaccharide modifications associated with resistance. DkcA was also shown to play a role in colistin resistance through maintenance of membrane potential at an optimum level. K. pneumoniae ΔdkcA was also compromised for virulence in a wax moth model of infection. In a different study, deletion of genes encoding DedA family proteins YqjA and YghB in K. pneumoniae resulted in a mutant strain with growth defects, alkaline sensitivity, and sensitivity to SDS and EDTA. These phenotypes can be reversed by adding divalent cations (Ca2+ or Mg2+) to the growth media. The alteration of divalent cation homeostasis in VT101 was shown to be due to hyperpolarization of its membrane potential. A similar strain in a virulent K. pneumoniae ST258 background was compromised in the synthesis of capsular polysaccharide resulting in a decrease of its virulence in an insect model and increased phagocytosis by murine alveolar macrophages. These studies provide insight into how the DedA superfamily contributes to the biology of K. pneumoniae. DedA proteins may be a pharmacological target to mitigate the challenges posed by virulent K. pneumoniae.
Tiwari, Vijay, "A Klebsiella Pneumoniae Membrane Protein Family Required for Antibiotic Resistance, Capsule Formation, and Virulence" (2023). LSU Doctoral Dissertations. 6214.
Dr. William Doerrler
Available for download on Wednesday, July 03, 2030