Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae

Abstract

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 (DspeE or Dcad) or transport genes (DpotABCD) 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 DspeE 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. Highthroughput 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.

Polyamine transporter in Streptococcus pneumoniae is essential for evading early innate immune responses in pneumococcal pneumonia

“…Previous studies showed that ΔspeE and Δcad were severely attenuated in a manner similar to Δ potABCD , in a mouse model of pneumococcal pneumonia18. Polyamine levels are stringently controlled by intracellular synthesis and transport mechanisms in pneumococci1826.…”

Putrescine Importer PlaP Contributes to Swarming Motility and Urothelial Cell Invasion in Proteus mirabilis

“…For example, in Salmonella enterica sv. typhimurium, polyamines are required for virulence (13); in Legionella pneumophila, intracellular growth is enhanced by polyamines derived from host cells (14), and in Streptococcus pneumoniae, polyamine biosynthetic pathways and the spermidine transporter PotABCD are important for infection (15,16).…”

Spermidine Biosynthesis and Transport Modulate Pneumococcal Autolysis

“…Another theory suggests that murein hydrolases are released to lyse neighboring noncompetent pneumococcal cells in a fratricidal manner, facilitating genetic exchange between naturally competent pneumococcal populations (39). The effect of spermidine utilization on autolysis demonstrated here may explain the previously characterized importance of polyamine biosynthetic and transport genes for pneumococcal colonization and pneumonia in the murine model of infection (14).…”

“…The first gene of this operon (SPD0809 in strain D39 [21]) is annotated as encoding either lysine decarboxylase or arginine decarboxylase (ADC) in different pneumococcal serotypes. It has been suggested that the primary role of this gene product in pneumococci is the decarboxylation of lysine to cadaverine (14). However, given the location of this gene on the pneumococcal chromosome, we hypothesized that it plays an important role in spermidine biosynthesis via arginine decarboxylation.…”