Identification and Characterization of Six Bacteriophages Capable of Infecting Extremely Antibiotic Resistant Strains of Stenotrophomonas maltophilia

• Author / Creator

  Peters, Danielle L.

• Infections caused by the ubiquitous Gram-negative bacillus Stenotrophomonas maltophilia are on the rise worldwide. Due to the impressive array of innate antibiotic resistance mechanisms employed by this bacterium, treatment of infections is exceedingly difficult; therefore, alternative treatment options are required. To combat these deadly infections, researchers around the world have shown a renewed interest in the use of phage therapy, or the clinical application of viruses parasitic to bacteria. To this end, six phages were isolated against three clinical isolates of S. maltophilia for characterization.The suitability of each phage was assessed for therapeutic use by analyzing the complete genome sequences. The genome sizes range from 42 to 168 kilobase pairs in length, and many of the phages show a surprising amount of diversity from any phage characterized to date. Of the six phages isolated, three have a lytic lifestyle and do not encode virulence factors. Two of the lytic phages, DLP1 and DLP2, have extended host ranges beyond S. maltophilia as they are capable of infecting strains of Pseudomonas aeruginosa. The third lytic phage, DLP6, is a T4- like Myoviridae phage with a moderate host range. These phages would be suitable for inclusion in a phage cocktail due to their lytic lifestyles and host ranges.In contrast to the lytic phages identified, the three temperate phages characterized would not be suitable for inclusion in a phage cocktail due to their ability to cause lysogenic conversion of their hosts. Phages DLP3 and DLP5 are identified as members of a novel genus, Delepquintavirus, due to their limited identity to other known phages. DLP3 lysogenization leads to an increase in erythromycin resistance and growth rate of its host strain. DLP5 is capable of lysogenizing its host as a phagemid and causes an increased growth rate during the lag and early exponential phase of growth. Phage DLP4 is capable of stable lysogeny even though no genes encoding proteins involved in a temperate lifestyle were identified. Lysogenization by DLP4 leads to increased trimethoprim resistance and the expression of a virulence factor known to increase swarming in Escherichia coli. Although only three lytic phages were identified as good candidates for phage therapy, characterization of the temperate phages offered insight into the important role phages play in the evolution of Stenotrophomonas maltophilia with respect to antibiotic resistance and putative virulence factors.

• Subjects / Keywords

  • Phage therapy
  • Bacteriophages
  • DLP3
  • DLP4
  • DLP5
  • Stenotrophomonas maltophilia
  • DLP2
  • DLP6
  • DLP1
  • Lysogenic conversion

• Graduation date

  Spring 2019

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-j4qn-4k55

• License

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