Abstract
Streptococcus pneumoniae is able to cause deadly diseases by infecting different tissues, each with distinct environmental and nutritional compositions. We hypothesize that the adaptive capabilities of the microbe is an important facet of pneumococcal survival in fluctuating host environments. Quorum-sensing (QS) mechanisms are pivotal for microbial host adaptation. We previously demonstrated that the TprA/PhrA QS system is required for pneumococcal utilization of galactose and mannose, neuraminidase activity, and virulence. We also showed that the system can be modulated by using linear molecularly imprinted polymers. Due to being a drugable target, we further studied the operation of this QS system in S. pneumoniae. We found that TprA controls the expression of nine different operons on galactose and mannose. Our data revealed that TprA expression is modulated by a complex regulatory network, where the master regulators CcpA and GlnR are involved in a sugar dependent manner. Mutants in the TprA/PhrA system are highly attenuated in their survival in nasopharynx and lungs after intranasal infection, and growth in blood after intravenous infection.
Highlights
Streptococcus pneumoniae causes an array of diseases with high morbidity and mortality including pneumonia, bacteraemia, meningitis, and otitis media (Weiser et al, 2018), especially among children and elderly
The TprA/PhrA system is induced by host-derived sugars, so we studied the influence of TprA on phrA in different sugar sources
The results showed that in the condition where the tprA promoter activity is high, that is in presence of mannose and galactose, TprA reduces PphrA-driven ß-galactosidase activity relative to its expression in the wild type D39 strain, indicating that TprA is a repressor of phrA (p < 0.01 and p < 0.001 in mannose and galactose, respectively) (Figure 1)
Summary
Streptococcus pneumoniae causes an array of diseases with high morbidity and mortality including pneumonia, bacteraemia, meningitis, and otitis media (Weiser et al, 2018), especially among children and elderly. The high incidence of pneumococcal diseases is compounded by a rising trend of antimicrobial resistance among pneumococcal strains This requires new approaches to develop anti-infectives against this microbe. QS systems have been implicated in wide range of biological functions, including surface attachment, oxidative stress resistance, microbial competition, and virulence (Federle, 2012; Cuevas et al, 2017; Zhi et al, 2018) These systems have received considerable attention not least because of their far-reaching impact on the fundamental biology of microbes and from the more applied perspective for their utility as anti-infective targets (Brooks and Brooks, 2014)
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