Abstract

Outer membrane protein A (OmpA) is a class of proteins highly conserved among the Enterobacteriaceae family and throughout evolution. Klebsiella pneumoniae is a capsulated gram-negative pathogen. It is an important cause of community-acquired and nosocomial pneumonia. Evidence indicates that K. pneumoniae infections are characterized by a lack of an early inflammatory response. Data from our laboratory indicate that K. pneumoniae CPS helps to suppress the host inflammatory response. However, it is unknown whether K. pneumoniae employs additional factors to modulate host inflammatory responses. Here, we report that K. pneumoniae OmpA is important for immune evasion in vitro and in vivo. Infection of A549 and normal human bronchial cells with 52OmpA2, an ompA mutant, increased the levels of IL-8. 52145-Δwca(K2)ompA, which does not express CPS and ompA, induced the highest levels of IL-8. Both mutants could be complemented. In vivo, 52OmpA2 induced higher levels of tnfα, kc, and il6 than the wild type. ompA mutants activated NF-κB, and the phosphorylation of p38, p44/42, and JNK MAPKs and IL-8 induction was via NF-κB-dependent and p38- and p44/42-dependent pathways. 52OmpA2 engaged TLR2 and -4 to activate NF-κB, whereas 52145-Δwca(K2)ompA activated not only TLR2 and TLR4 but also NOD1. Finally, we demonstrate that the ompA mutant is attenuated in the pneumonia mouse model. The results of this study indicate that K. pneumoniae OmpA contributes to attenuate airway cell responses. This may facilitate pathogen survival in the hostile environment of the lung.

Highlights

  • The OM3 of Gram-negative bacteria is composed of phospholipids, LPS, and outer membrane proteins

  • We demonstrate that the ompA mutant is attenuated in the pneumonia mouse model

  • At 8 h postinfection, ompA mutants induced higher levels of IL-8 than the parental strains, 52145-⌬wcaK2ompA being the strain inducing the highest levels. Both mutants were complemented (Fig. 1D). These data show that CPS and Outer membrane protein A (OmpA) are bacterial factors required to reduce the secretion of IL-8 by airway epithelial cells upon K. pneumoniae infection

Read more

Summary

Introduction

The OM3 of Gram-negative bacteria is composed of phospholipids, LPS, and outer membrane proteins. A wealth of evidence indicates that activation of inflammatory responses is essential to clear Klebsiella infections (26 –28) and that TLRs seem to play a major role in detecting K. pneumoniae [29, 30]. This suggests that K. pneumoniae may somehow try to counteract the induction of these host defense responses. Whether K. pneumoniae employs additional factors to modulate host inflammatory responses is still unknown In this context, several studies have shown that recombinant purified OmpA from K. pneumoniae induces the expression of inflammatory molecules in a TLR2-dependent manner in various cell types [33,34,35]. There might be differences between the cellular recognition of recombinant purified OmpA and OmpA expressed in the complex lipid environment of the bacterial OM, and the cellular responses could be different

Objectives
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call