Exposure of a 23F Serotype Strain ofStreptococcus pneumoniaeto Cigarette Smoke Condensate Is Associated with Selective Upregulation of Genes Encoding the Two-Component Regulatory System 11 (TCS11)

Abstract

Alterations in whole genome expression profiles following exposure of the pneumococcus (strain 172, serotype 23F) to cigarette smoke condensate (160 μg/mL) for 15 and 60 min have been determined using the TIGR4 DNA microarray chip. Exposure to CSC resulted in the significant (P < 0.014–0.0006) upregulation of the genes encoding the two-component regulatory system 11 (TCS11), consisting of the sensor kinase, hk11, and its cognate response regulator, rr11, in the setting of increased biofilm formation. These effects of cigarette smoke on the pneumococcus may contribute to colonization of the airways by this microbial pathogen.

The effects of e-cigarette vapor exposure on the transcriptome and virulence of Streptococcus pneumoniae

“…Notably, we did not observe upregulation of genes encoding TCS11 (SP_2000/SP_2001) in CSE-TIGR4 or in EVE +NIC -TIGR4 (Table 1). These results contradict previous observations that CS exposure upregulates transcription of TCS11 genes in pneumococcal serotypes 19F and 23F indicating the strain-dependent nature of these effects [18, 19]. Both CSE-TIGR4 and EVE +NIC -TIGR4 also exhibited altered expression of genes involved in carbon uptake and metabolism (phosphotranferase systems/PTS), pneumococcal stress response (Clp proteases, hrcA /SP_0515) and transcriptional regulators ( mgrA /SP_1800, marR /SP_1863, merR /SP_1856) and (Table 2).…”

“…Compared to previous studies analyzing the effects of CS exposure on the pneumococcal transcriptome, the main discrepancy was observed in the expression genes encoding TCS11. Previous studies have reported that exposure to CS induces upregulation of TCS11 (SP_2000, SP_2001) expression in two different pneumococcal strains (serotypes 19F and 23F) and that TCS11 activity plays a role in pneumococcal biofilm formation but not in virulence in a mouse model [18, 19, 47]. However, we did not detect significant changes in the expression of TCS11 genes in any of our treatment groups.…”

“…Here, we exposed TIGR4 (serotype 4) for 2h to CSE generated by burning Marlboro cigarettes. In contrast, Manna et al exposed S. pneumoniae strain EF3030 (serotype 19F) for 45 min to CSE from research grade cigarettes, whereas Cockeran et al exposed strain 172 (serotype 23F) to 160 μg/ml cigarette smoke condensate [18, 19]. Since biofilm formation was enhanced in both CSE-TIGR4 and EVE +NIC -TIGR4 we can also argue that CSE and EVE +NIC can enhance TIGR4 biofilms in an TCS11-indepdent manner.…”

“…Importantly, CS-exposed staphylococci with augmented virulence have been shown to induce higher pulmonary bacterial burden and increased mortality in mouse models of acute pneumonia [15, 16]. In S. pneumoniae , the effects of CS exposure on virulence are limited to the induction of biofilm formation and significant attenuation of the activity of pore-forming toxin pneumolysin ( ply) gene; [17, 18]. At the transcriptomic level, in vitro , acute CS exposure is reported to alter the expression of genes encoding factors required primarily for pneumococcal stress response and survival, as well as significantly downregulating ply expression without affecting the expression of other virulence genes [18, 19].…”

“…In S. pneumoniae , the effects of CS exposure on virulence are limited to the induction of biofilm formation and significant attenuation of the activity of pore-forming toxin pneumolysin ( ply) gene; [17, 18]. At the transcriptomic level, in vitro , acute CS exposure is reported to alter the expression of genes encoding factors required primarily for pneumococcal stress response and survival, as well as significantly downregulating ply expression without affecting the expression of other virulence genes [18, 19]. To date, the pathogenesis of CS-exposed pneumococci has not been examined in a mouse model of respiratory tract infection.…”