Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae.
Polyamines such as cadaverine, putrescine and spermidine are polycationic molecules that have pleiotropic effects on cells via their interaction with nucleic acids. Streptococcus pneumoniae (the pneumococcus) is a Gram-positive pathogen capable of causing pneumonia, septicaemia, otitis media and meningitis. Pneumococci have a polyamine transport operon (potABCD) responsible for the binding and transport of putrescine and spermidine, and can synthesize cadaverine and spermidine using their lysine decarboxylase (cad) and spermidine synthase (speE) enzymes. Previous studies from our laboratory have shown that an increase in PotD expression is seen following exposure to various stresses, while during infection, potD inactivation significantly attenuates pneumococcal virulence, and anti-PotD immune responses are protective in mice. In spite of their relative importance, not much is known about the global contribution of polyamine biosynthesis and transport pathways to pneumococcal disease. Mutants deficient in polyamine biosynthesis (ΔspeE or Δcad) or transport genes (ΔpotABCD) were constructed and were found to be attenuated in murine models of pneumococcal colonization and pneumonia, either alone or in competition with the wild-type strain. The ΔspeE mutant was also attenuated during invasive disease, while the potABCD and cad genes seemed to be dispensable. HPLC analyses showed reduced intracellular polyamine levels in all mutant strains compared with wild-type bacteria. High-throughput proteomic analyses indicated reduced expression of growth, replication and virulence factors in mutant strains. Thus, polyamine biosynthesis and transport mechanisms are intricately linked to the fitness, survival and pathogenesis of the pneumococcus in host microenvironments, and may represent important targets for prophylactic and therapeutic interventions.
Shah
Pratik
P
Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Nanduri
Bindu
B
College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
Swiatlo
Edwin
E
Research Service, Veteran Affairs Medical Center, 1500 East Woodrow Wilson Drive, Jackson, MS 39216, USA.
Ma
Yinfa
Y
Department of Chemistry, Missouri University of Science and Technology, Rolla, MO 65409, USA.
Pendarvis
Ken
K
College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
D000143:Acids / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D004269:DNA, Bacterial / Q000235:genetics; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009154:Mutation; D018384:Oxidative Stress; D011018:Pneumonia, Pneumococcal / Q000382:microbiology*; D011073:Polyamines / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
D000143:Acids; D004269:DNA, Bacterial; D011073:Polyamines; D020543:Proteome