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Open Access Highly Accessed Research article

Toxin-antitoxin loci vapBC-1 and vapXD contribute to survival and virulence in nontypeable Haemophilus influenzae

Dabin Ren14, Anna N Walker2 and Dayle A Daines3*

Author Affiliations

1 Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA, USA

2 Department of Pathology, Mercer University School of Medicine, Macon, GA, USA

3 Department of Biological Sciences, Old Dominion University, Norfolk, VA, USA

4 Current address: Rochester General Hospital Research Institute, Rochester, NY, USA

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BMC Microbiology 2012, 12:263  doi:10.1186/1471-2180-12-263

Published: 19 November 2012

Abstract

Background

Nontypeable Haemophilus influenzae (NTHi) is a significant human pathogen responsible for respiratory tract infections and the most common cause of recurrent otitis media. Type II toxin-antitoxin (TA) systems are genetic elements that code for a stable protein toxin and a labile antitoxin that are thought to be involved in metabolic regulation of bacteria by enabling a switch to a dormant state under stress conditions. The contribution to infection persistence of the NTHi TA loci vapBC-1 and vapXD was examined in this study.

Results

Deletions in vapBC-1, vapXD and vapBC-1 vapXD significantly decreased the survival of NTHi co-cultured with primary human respiratory tissue at the air-liquid interface and in the chinchilla model of otitis media. The TA deletions did not affect the growth dynamics of the mutants in rich media, their ultra-structural morphology, or display appreciable synergy during NTHi infections. The toxin and antitoxin proteins of both pairs heterodimerized in vivo. Consistent with our previous findings regarding the VapC-1 toxin, the NTHi VapD toxin also displayed ribonuclease activity.

Conclusions

We conclude that the vapBC-1 and vapXD TA loci enhance NTHi survival and virulence during infection in vitro and in vivo using a mechanism of mRNA cleavage, and that these conserved TA pairs represent new targets for the prophylaxis and therapy of otitis media and other NTHi-caused mucosal diseases.

Keywords:
NTHi; Otitis media; Protein-protein interactions; Stress; Ribonuclease