Thus, we examined the cell adhesion activity of a phosphocholine-deficient S.

pneumoniae mutant (Fig. 5). The adherence of the phosphocholine-deficient mutant was slightly upregulated by RSV infection compared to the parent strain R6. The upregulation by RSV infection in R6 was significantly suppressed in the presence of fosfomycin, whereas the adhesion of the mutant to A549 cells was not significantly altered by fosfomycin treatment. These results indicated that fosfomycin suppressed S. pneumoniae and H. influenzae adhesion in a PAF receptor-dependent manner via bacterial phosphocholine. Several clinical isolates of S. pneumoniae and H. influenzae were also assessed. Similar RSV-induced bacterial adhesion and significant suppression by fosfomycin, as well as PAF receptor antagonist occurred (Fig. Linsitinib 6). Furthermore, both strains of RSV, Long and A2, yielded comparable results for upregulation of the PAF receptor and the inhibitory effect of fosfomycin on PAF receptor induction (data not shown). These lines of evidence confirm that the expression of the PAF receptor is induced by RSV infection and indicate that this

induction is suppressed by fosfomycin treatment. Recently, we reported that fosfomycin suppressed the RSV-induced production of chemokines, such as interleukin-8 (IL-8) and ‘regulated on activation, normal click here T-cell expressed and secreted’ (RANTES), in the respiratory epithelial cell line A549, but that it did not affect virus replication (Okabayashi et al., 2009). The suppression of chemokine induction by RSV is due to the downregulation of NF-κB activation (Okabayashi HSP90 et al., 2009). Yoneshima et al. (2003) also reported the suppression of NF-κB activation by fosfomycin in the human monocytic cell line U937 and in the T-cell line Jurkat stimulated with Gram-negative bacterial lipopolysaccharides. The PAF receptor is a receptor for S. pneumoniae and H. influenzae (Cundell et al., 1995; Swords et al., 2000). Transcription of the PAF receptor gene is controlled by NF-κB (Mutoh et al.,

1994; Shimizu & Mutoh, 1997). Ishizuka et al. (2001) showed that the specific NF-κB inhibitor PDTC suppressed acid-induced S. pneumoniae adhesion to A549 cells via the suppression of PAF receptor induction. Hence, the suppression of PAF receptor expression by fosfomycin seems to be due to the suppression of NF-κB activation. Respiratory viruses, including RSV, induce PAF receptors and bacterial adhesion via it (Ishizuka et al., 2003; Avadhanula et al., 2006). In the present study, we showed that fosfomycin suppressed S. pneumoniae and H. influenzae adhesion to RSV-infected A549 cells. The bacterial adhesion was suppressed by the PAF antagonist and the anti-PAF receptor antibody. On the other hand, the phosphocholine-deficient S. pneumoniae mutant did not show RSV-induced adhesion, which was suppressed by fosfomycin.