| Titel |
Pathological and therapeutic significance of cellular invasion by Proteus mirabilis in an enterocystoplasty infection stone model |
| Gepubliceerd in |
Infection and Immunity. ISSN 0019-9567. |
| Auteur |
Mathoera, R.B.; Kok, D.J. (Dirk); Verduin, C.M. (Cees); Nijman, J.M. (Rien) |
| Datum |
2002-01-01 |
| Trefwoord(en) |
Child, Cell Line, Humans, Microscopy, Confocal, *Drug Resistance, Bacterial, Anti-Bacterial Agents/*pharmacology, Bacterial Adhesion, Culture Media, Intestines/cytology/*microbiology, Microscopy, Electron, Mucins/metabolism, Proteus Infections/microbiology, Proteus mirabilis/*drug effects/*pathogenicity, Ureter/cytology/*microbiology, Urinary Calculi, Urine/microbiology |
| Taal |
Engels |
| Type |
artikel |
| Samenvatting |
Proteus mirabilis infection often leads to stone formation. We evaluated
how bacterium-mucin adhesion, invasion, and intracellular crystal
formation are related to antibiotic sensitivity and may cause frequent
stone formation in enterocystoplasties. Five intestinal (Caco-2, HT29,
HT29-18N2, HT29-FU, and HT29-MTX) and one ureter cell line (SV-HUC-1) were
incubated in artificial urine with five Proteus mirabilis strains.
Fluorescence-activated cell sorting (FACS), laser scanning microscopy, and
electron microscopy evaluated cellular adhesion and/or invasion,
pathologic changes to mitochondria, and P. mirabilis-mucin colocalization
(MUC2 and MUC5AC). An MTT (thiazolyl blue tetrazolium bromide) assay and
FACS analysis of caspase-3 evaluated the cellular response. Infected cells
were incubated with antibiotics at dosages representing the expected
urinary concentrations in a 10-year-old, 30-kg child to evaluate bacterial
invasion and survival. All cell lines showed colocalization of P.
mirabilis with human colonic mucin (i.e., MUC2) and human gastric mucin
(i.e., MUC5AC). The correlation between membrane mucin expression and
invasion was significant and opposite for SV-HUC-1 and HT29-MTX.
Microscopically, invasion by P. mirabilis with intracellular crystal
formation and mitochondrial damage was found. Double membranes surrounded
bacteria in intestinal cells. Relative resistance to cotrimoxazole and
augmentin was found in the presence of epithelial cells. Ciprofloxacin and
gentamicin remained effective. Membrane mucin expression was correlated
with relative antibiotic resistance. Cell invasion by P. mirabilis and
mucin- and cell type-related distribution and response differences
indicate bacterial tropism that affects crystal formation and mucosal
presence. Bacterial invasion seems to have cell type-dependent mechanisms
and prolong bacterial survival in antibiotic therapy, giving a new target
for therapeutic optimalization of antibiotic treatment. |
| Publicatie |
http://hdl.handle.net/1765/10018 |
| Persistent Identifier |
urn:NBN:nl:ui:15-1765/10018 |
| Metadata |
XML |
| Repository |
Erasmus Universiteit Rotterdam |