Gastrointestinal (GI) colonization by Klebsiella pneumoniae is a risk factor for subsequent infection as well as transmission to other patients. Additionally, colonization is achieved by many strain types that exhibit high diversity in genetic content. However, how K. pneumoniae achieves colonization and whether the genetic factors it uses differ by strain is not well understood. In this dissertation, we developed a mouse model of GI colonization which supported studies into how strains differ in their colonization capacities and how colonization factors are shared or strain-specific. We found that strain-to-strain differences in colonization fitness could be quantified in competition in vivo. Additionally, we created saturating transposon mutant libraries in three clinical isolates of K. pneumoniae to screen for colonization factors in vivo. With these genomic screens, we identified a core colonization program as well as strain-specific colonization factors. Furthermore, we validated three shared colonization factors (acrA, carAB, and tatABCD), one factor which provided a colonization advantage when disrupted (malT), and two factors which were strain specific (hha and scrY) Thus, our data provide insight into how a global pathogen of concern establishes gastrointestinal colonization. Our approach reveals that understanding pathogenesis in species with high genomic diversity requires examination of multiple genetically distinct strains.

Creator

• Cheung, Bettina

DOI

• https://doi.org/10.21985/n2-0pcc-2k97

Subject

• Microbiology
• Medicine

Language

• en

Alternate Identifier

• http://dissertations.umi.com/northwestern:16716
• etdadmin_upload_1012335

Keyword

• Klebsiella pneumoniae
• Genomics
• Transposon mutant screen
• Gastroinestinal colonization

Date created

• 2023-01-01

Resource type

• Dissertation

Rights statement

• In Copyright