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Extended-spectrum antibodies protective against carbapenemase-producing Enterobacteriaceae.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2016 Apr; Vol. 71 (4), pp. 927-35. Date of Electronic Publication: 2016 Jan 07. - Publication Year :
- 2016
-
Abstract
- Background: Carbapenem-resistant Enterobacteriaceae (CRE) are responsible for worldwide outbreaks and antibiotic treatments are problematic. The polysaccharide poly-(β-1,6)-N-acetyl glucosamine (PNAG) is a vaccine target detected on the surface of numerous pathogenic bacteria, including Escherichia coli. Genes encoding PNAG biosynthetic proteins have been identified in two other main pathogenic Enterobacteriaceae, Enterobacter cloacae and Klebsiella pneumoniae. We hypothesized that antibodies to PNAG might be a new therapeutic option for the different pan-resistant pathogenic species of CRE.<br />Methods: PNAG production was detected by confocal microscopy and its role in the formation of the biofilm (for E. cloacae) and as a virulence factor (for K. pneumoniae) was analysed. The in vitro (opsonophagocytosis killing assay) and in vivo (mouse models of peritonitis) activity of antibodies to PNAG were studied using antibiotic-susceptible and -resistant E. coli, E. cloacae and K. pneumoniae. A PNAG-producing strain of Pseudomonas aeruginosa, an organism that does not naturally produce this antigen, was constructed by adding the pga locus to a strain with inactive alg genes responsible for the production of P. aeruginosa alginate. Antibodies to PNAG were tested in vitro and in vivo as above.<br />Results: PNAG is a major component of the E. cloacae biofilm and a virulence factor for K. pneumoniae. Antibodies to PNAG mediated in vitro killing (>50%) and significantly protected mice against the New Delhi metallo-β-lactamase-producing E. coli (P = 0.02), E. cloacae (P = 0.0196) and K. pneumoniae (P = 0.006), against K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (P = 0.02) and against PNAG-producing P. aeruginosa (P = 0.0013). Thus, regardless of the Gram-negative bacterial species, PNAG expression is the sole determinant of the protective efficacy of antibodies to this antigen.<br />Conclusions: Our findings suggest antibodies to PNAG may provide extended-spectrum antibacterial protective activity.<br /> (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Biofilms
Drug Resistance, Bacterial drug effects
Enterobacteriaceae enzymology
Mice
Virulence Factors immunology
Antibodies, Bacterial pharmacology
Bacterial Proteins biosynthesis
Bacterial Proteins genetics
Bacterial Vaccines immunology
Enterobacteriaceae genetics
Enterobacteriaceae Infections microbiology
Enterobacteriaceae Infections prevention & control
beta-Glucans immunology
beta-Lactamases biosynthesis
beta-Lactamases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 71
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 26747103
- Full Text :
- https://doi.org/10.1093/jac/dkv448