Extended-spectrum beta-lactamase production is associated with an increase in cell invasion and expression of fimbrial adhesins in Klebsiella pneumoniae.
Extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae strains are suggested to possess higher pathogenic potential than non-ESBL producers. Microbial adherence to and invasion of host cells are critical steps in the infection process, so we examined the expression of type 1 and 3 fimbrial adhesins by 58 ESBL-producing and 152 nonproducing isolates of K. pneumoniae and their abilities to invade ileocecal and bladder epithelial cells. Mannose-sensitive hemagglutination of guinea pig erythrocytes and mannose-resistant hemagglutination of ox erythrocytes were evaluated to determine the strains' abilities to express type 1 and type 3 fimbriae, respectively. Bacterial adhesion to and invasion of epithelial cells were tested by enzyme-linked immunosorbent assay and imipenem killing assay, respectively. The adherence of ESBL- and non-ESBL-producing strains to epithelial cells did not differ significantly (P > 0.05). In contrast, the proportion of strains capable of invading (>5% relative invasion) ileocecal and bladder epithelial cells was significantly higher among ESBL producers (81%, n = 47/58, and 27.6%, n = 16/58, respectively) than among non-ESBL producers (61%, n = 93/152, and 10%, n = 15/152, respectively) (P = 0.0084, odds ratio [OR] = 2.711, 95% confidence interval [CI] = 1.302 to 5.643 and P = 0.0021, OR = 4.79, 95% CI = 1.587 to 7.627). The mean invasion by ESBL producers (5.5% +/- 2.8% and 3.3% +/- 2.7%, respectively) was significantly higher than that by non-ESBL producers (2.9% +/- 2.6% and 1.8% +/- 2%, respectively) (P < 0.0001). Likewise, the proportion of ESBL producers coexpressing both fimbrial adhesins was significantly higher (79.3%; n = 46/58) than that of non-ESBL producers (61.8%; n = 94/152) (P = 0.0214; OR = 2,365; 95% CI = 1.157 to 4.834). Upon acquisition of SHV-12-encoding plasmids, two transconjugants switched on to produce type 3 fimbriae while expression of type 1 fimbriae was not affected. The acquisition of an ESBL plasmid appeared to upregulate the phenotypic expression of one or more genes, resulting in greater invasion ability.
Institute for Infection Medicine, Faculty of Medicine, University of Kiel, Kiel, Germany. sahly@labor-lademannbogen.de
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H
Sahly
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S
Navon-Venezia
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L
Roesler
A
A
Hay
Y
Y
Carmeli
R
R
Podschun
C
C
Hennequin
C
C
Forestier
I
I
Ofek
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D002432:Cecum / Q000166:cytology; D002460:Cell Line; D003227:Conjugation, Genetic; D004847:Epithelial Cells / Q000382:microbiology*; D004912:Erythrocytes / Q000382:microbiology / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D006168:Guinea Pigs; D006384:Hemagglutination; D006801:Humans; D007082:Ileum / Q000166:cytology; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008826:Microbial Sensitivity Tests; D001743:Urinary Bladder / Q000166:cytology; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
D018829:Adhesins, Bacterial; C107198:beta-lactamase SHV-12; D001618:beta-Lactamases