Streptococcus pneumoniae Rapidly Translocate from the Nasopharynx through the Cribriform Plate to Invade the Outer Meninges

Abstract

Using two-photon imaging, we show that pneumococci translocate from the nasopharynx to the dorsal meninges of a mouse in the absence of any bacteria found in blood or cerebrospinal fluid. Strikingly, this takes place within minutes of inhaled delivery of pneumococci, suggesting the existence of an inward flow of fluid connecting the nasopharynx to the meninges, rather than a receptor-mediated mechanism.

The Streptococcus pneumoniae transcriptome in patient cerebrospinal fluid identifies novel virulence factors required for meningitis

“…The effects of mutation of bgaA or Sp_1801-05 was assessed in a recently developed mouse model of brain infection involving nasopharyngeal translocation of S. pneumoniae to the brain 55 . Both the Δ bgaA and Δ Sp_1801-05 strains successfully colonised the nasopharynx and were able to reach the olfactory epithelium and olfactory bulb with similar CFU levels at all three sites compared to the WT strain ( Figure 4A ).…”

“…In contrast, brain infection occurred in 50% of mice infected with WT, demonstrating that both bgaA and Sp_1801-05 were required for brain infection. Next, we tested the virulence of the two mutant strains in a zebra fish meningitis model requiring direct injection of S. pneumoniae into the hindbrain CSF 55,56 . Zebra fish injected with the Δ bgaA strain had improved survival compared to those injected with the Δ Sp_1801-05 or WT strains, although there were no differences in either bacterial CFU recovered from the fish brain or neutrophil ingress ( Figures 4B and C ).…”

“…S. pneumoniae deletion mutant strains were tested in a mouse model of nasopharynx-to-brain translocation model previously described. 55 Groups of 5 mice anaesthetized with 2.5% isoflurane and intranasally inoculated with a 10 μl suspension containing 10 8 CFU of wild-type, Δ bgaA or Δ Sp_1801-05 strains. At predetermined time points, mice were culled and the CFU were determined at 0, 3, 7, and 10 days post-inoculation in tissue samples including the nasopharynx (NP), olfactory bulb (OB), olfactory epithelium (OE) and Brain (Br) as previously described.…”

“…At predetermined time points, mice were culled and the CFU were determined at 0, 3, 7, and 10 days post-inoculation in tissue samples including the nasopharynx (NP), olfactory bulb (OB), olfactory epithelium (OE) and Brain (Br) as previously described. 55 Blood was also checked for CFU at 3, 7 and 10 days post-infection, and no bacteria were detected in blood at any timepoint.…”

Spatio-temporal brain invasion pattern ofStreptococcus pneumoniaeand dynamic changes of the cellular environment in meningitis pathogenesis

“…Pneumococcal meningitis, the inflammation of the meninges caused by the Gram-positive bacterium Streptococcus pneumoniae (the pneumococcus), is a medical emergency, with a mortality ranging between 18-30%, depending on the geographical region, with half of survivors suffering from long-term neurological sequelae, most commonly hearing loss, motor disabilities and cognitive impairments [1]. In the majority of pneumococcal meningitis cases, invasion into the brain and meninges follows a hematogenous route of infection, although translocation from the nasopharynx through the cribriform plate or through direct implementation in the brain following trauma or surgery does occur [2][3][4]. The presence of S. pneumoniae in the brain causes a vast inflammatory response, with release of reactive oxidative species and matrix metalloproteinases that augments pathological progression [5].…”