While microbial competition during infection has most often been examined at the genus or species level [1, 2], the dissertation work described herein asked whether interstrain competition plays an important role in determining which bacterial lineages emerge to cause disease. The goal of this dissertation was to examine the strain population dynamics during mixed-strain bacterial pneumonia to characterize how interstrain competition influences species pathogenicity and the establishment of pneumonia. Through these studies, it may be possible to identify strains with the proclivity to outcompete in the host environment, establish infection, and therefore persist as successful pathogens in clinical settings. Herein a method called “StrainSeq” was developed to enumerate relative strain numbers during mixed Klebsiella pneumoniae or Acinetobacter baumannii infections in the murine model of acute pneumonia without barcoding. Following infection with a combination of K. pneumoniae or A. baumannii strains, a single strain consistently achieved marked numerical dominance by 20 hours post-infection in both bacterial species. Transposon mutagenesis screening revealed that genes involved in transcriptional regulation and metabolic pathways were important for K. pneumoniae competitive strain outgrowth during mixed infections. Furthermore, three K. pneumoniae genes were identified that contributed to the ability of a particular strain to outcompete other K. pneumoniae strains in the pulmonary environment. Through growth analysis of several K. pneumoniae strains under varying nutrient availabilities, it was determined that strain dominance during infection may be promoted by specialized metabolic pathways to promote competitive strain outgrowth in vivo. The data described herein suggest that single strains will competitively outgrow in the lung environment during mixed infections by K. pneumoniae or A. baumannii to establish disease. This strain dominance phenomenon is likely to occur in multiple bacterial species. Further, modified transcriptional regulation and distinct metabolic advantages of competitive strains may promote in-host fitness to support the outgrowth of a single bacterial lineage. This work provides insight in strain diversity during the establishment of pneumonia and elucidates mechanisms to describe strain outgrowth during mixed infections.

Creator

• Agard, Mallory

DOI

• https://doi.org/10.21985/n2-khcg-sb88

Subject

• Microbiology
• Immunology

Language

• en

Alternate Identifier

• http://dissertations.umi.com/northwestern:14551
• etdadmin_upload_647535

Keyword

• Klebsiella pneumoniae
• Pneumonia
• Strain Identification
• StrainSeq
• Acinetobacter baumannii

Date created

• 2019-01-01

Resource type

• Dissertation

Rights statement

• In Copyright