title: Toxin-antitoxin loci vapBC-1 and vapXD contribute to survival and virulence in nontypeable Haemophilus influenzae.
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.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA, USA.
authors.forename: Dabin
authors.initials: D
authors.lastname: Ren
authors.forename: Anna N
authors.initials: AN
authors.lastname: Walker
authors.forename: Dayle A
authors.initials: DA
authors.lastname: Daines
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002682:Chinchilla; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006193:Haemophilus influenzae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D050296:Microbial Viability; D010033:Otitis Media / Q000382:microbiology / Q000473:pathology; D055503:Protein Multimerization; D020545:Respiratory Mucosa / Q000382:microbiology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D037521:Virulence Factors