Interconversion of Purine Mononucleotides in Pasteurella pestis

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Virulence in *Pasteurella pestis* is multifactorial, with purine biosynthesis and colony pigmentation identified as key determinants.
• The ability to synthesize purines de novo and form dark pigmented (P(+)) colonies are established virulence factors.

Purpose of the Study:

• To investigate the relationship between purine metabolism, colony pigmentation, and virulence in *Pasteurella pestis*.
• To elucidate the role of specific purine biosynthesis pathways in *P. pestis* virulence.

Main Methods:

• Utilized radiolabeled guanine and adenine to trace nucleic acid precursor conversion in *P. pestis* strains.
• Cultivated P(+) and P(-) isolates in minimal and enriched media to assess pigmentation and metabolic pathways.
• Determined median lethal dose (LD50) in mice and guinea pigs for purine auxotroph mutants.

Main Results:

• P(+) isolates in minimal media failed to convert guanine to adenine in RNA, indicating a block in de novo purine synthesis.
• This conversion was restored in enriched media, and observed in P(-) mutants under all conditions.
• A deficiency in adenine deaminase was suggested by differential conversion of adenine isotopes.
• Purine auxotrophs with blocks early in the pathway had higher LD50 values than those with later blocks.

Conclusions:

• *Pasteurella pestis* virulence is significantly influenced by the efficiency of its purine biosynthesis pathway.
• Specific blocks in purine metabolism, particularly those affecting the de novo synthesis of inosine monophosphate, drastically reduce the organism's virulence in mammalian models.
• Colony pigmentation is linked to purine metabolism, suggesting a complex interplay of these factors in pathogenesis.