Infect Immun. 2014 Oct 13. pii: IAI.02434-14. [Epub ahead of print]
Ethanol-induced alcohol dehydrogenase E (AdhE) potentiates pneumolysin in Streptococcus pneumoniae.
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Abstract
Alcohol impairs the host immune system, rendering hosts more vulnerable to infection. Therefore, alcoholics are at increased risk of acquiring serious bacterial infections caused by Streptococcus pneumoniae, including pneumonia. Nevertheless, how alcohol affects pneumococcal virulence remains unclear. Here we showed that S. pneumoniae type 2 D39 is ethanol tolerant, and that alcohol up-regulates alcohol dehydrogenase E (AdhE) and potentiates pneumolysin (Ply). Hemolytic activity, colonization, and virulence of S. pneumoniae, as well as host cell myeloperoxidase activity, pro-inflammatory cytokine secretion, and inflammation, were significantly attenuated in adhE mutant bacteria (ΔadhE) compared to D39 wild-type bacteria. Therefore, AdhE might act as a pneumococcal virulence factor. Moreover, in the presence of ethanol, S. pneumoniae AdhE produced acetaldehyde and NADH, which subsequently led Rex (redox-sensing transcriptional repressor) to dissociate from the adhE promoter. An increase in AdhE in the ethanol condition conferred an increase of Ply and H2O2 levels. Consistently, S. pneumoniae D39 caused higher cytotoxicity to RAW 264.7 cells than ΔadhE during the ethanol stress condition, and alcoholic mice were more susceptible to infection with the D39 wild-type bacteria than the ΔadhE. Taken together, these data indicate that AdhE increases Ply in the ethanol stress condition, thus potentiating pneumococcal virulence.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
PMID: 25312953 [PubMed - as supplied by publisher]
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