Download Impaired pneumococcal polyamine transport effects on host and

Impaired pneumococcal polyamine transport effects on host and bacterial protein
expression.
Aswathy N. Rai1, Leslie A. Shack1, Seongbin Park1, Edwin Swiatlo2 and Bindu Nanduri1
1
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University,
Mississippi State, MS, 39762.
2
Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, MS, 39216.
Streptococcus pneumoniae is the most common cause of community acquired pneumonia and a
leading cause of meningitis, sinusitis, chronic bronchitis, and otitis media. Polyamine transport
genes are conserved, and provide a potential new class of therapeutic targets, as deletion of
polyamine transport operon (potABCD) in S. pneumoniae TIGR4 (WT) led to attenuation in a
mouse model of pneumonia. Our preliminary findings showed that polyamine transport deletion
strain (PTm) gets cleared by host defenses 24h post infection (p.i.). Here, we report evaluation of
both host and pneumococcal protein expression, to identify molecular mechanisms that could
result in reduced virulence of PTm. We performed intranasal challenge with 1 X 107 WT and PTm
strains and harvested lung 4h, and 12h p.i. Proteins were isolated from mouse lung and bacteria
cultured in vitro and subjected to1D LC ESI MS/MS. Our results demonstrate early activation of
inflammatory networks by PTm (4h) compared to the WT (12h) in infected lung. Significant
decrease in the expression of pneumococcal capsular polysaccharide biosynthesis protein
(Cps4F) was observed with PTm, which could render it more susceptible to host defenses. Dot
blot with serotype specific antibody confirmed reduced capsule in PTm, which could explain
attenuation in vivo. Grant support: This work was funded by Grant # P20GM103646 (Center for
Biomedical Research Excellence in Pathogen Host Interactions) from the National Institute for
General Medical Sciences.