The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection.

Ana Antunes,Aude Terrade,Josef Deutscher,Isabel Delany,Ala-Eddine Deghmane,Meriem Derkaoui,Muhamed-Kheir Taha,Mélanie Denizon

doi:10.1371/journal.pone.0162434

Abstract

Neisseria meningitidis is an exclusively human pathogen frequently carried asymptomatically in the nasopharynx but it can also provoke invasive infections such as meningitis and septicemia. N. meningitidis uses a limited range of carbon sources during infection, such as glucose, that is usually transported into bacteria via the phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS), in which the phosphocarrier protein HPr (encoded by the ptsH gene) plays a central role. Although N. meningitidis possesses an incomplete PTS, HPr was found to be required for its virulence. We explored the role of HPr using bioluminescent wild-type and ΔptsH strains in experimental infection in transgenic mice expressing the human transferrin. The wild-type MC58 strain was recovered at higher levels from the peritoneal cavity and particularly from blood compared to the ΔptsH strain. The ΔptsH strain provoked lower levels of septicemia in mice and was more susceptible to complement-mediated killing than the wild-type strain. We tested whether meningococcal structures impacted complement resistance and observed that only the capsule level was decreased in the ΔptsH mutant. We therefore compared the transcriptomic profiles of wild-type and ΔptsH strains and identified 49 differentially expressed genes. The HPr regulon contains mainly hypothetical proteins (43%) and several membrane-associated proteins that could play a role during host interaction. Some other genes of the HPr regulon are involved in stress response. Indeed, the ΔptsH strain showed increased susceptibility to environmental stress conditions. Our data suggest that HPr plays a pleiotropic role in host-bacteria interactions most likely through the innate immune response that may be responsible for the enhanced clearance of the ΔptsH strain from blood.

Highlights

Neisseria meningitidis is a Gram-negative bacterium belonging to the β-subgroup of proteobacteria
Meningococcus has evolved several redundant mechanisms to evade the host innate responses at the site of colonization and during systemic growth. These include the capsule which is important for serum resistance [6] and essential to sustain septicemia in a transgenic mouse model expressing human transferrin [7], the factor H binding protein [8, 9], neisserial surface protein A (NspA) [10, 11] and PorB2 [12], that regulate the alternative pathway (AP) of complement activation, lipooligosaccharide (LOS) sialic acid, which inhibits complement deposition, and NalP that cleaves human complement C3 [13]
In this work we explored the role of HPr during infection using transgenic mice expressing the human transferrin that allows meningococcal growth by providing both iron and carbon sources [22]

Summary

Introduction

Neisseria meningitidis is a Gram-negative bacterium belonging to the β-subgroup of proteobacteria. Meningococcus has evolved several redundant mechanisms to evade the host innate responses at the site of colonization and during systemic growth These include the capsule which is important for serum resistance [6] and essential to sustain septicemia in a transgenic mouse model expressing human transferrin [7], the factor H binding protein (fHbp) [8, 9], neisserial surface protein A (NspA) [10, 11] and PorB2 [12], that regulate the alternative pathway (AP) of complement activation, lipooligosaccharide (LOS) sialic acid, which inhibits complement deposition, and NalP that cleaves human complement C3 [13]. In this work we explored the role of HPr during infection using transgenic mice expressing the human transferrin that allows meningococcal growth by providing both iron and carbon sources [22]

Ethics statement

Results

Discussion