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产超广谱β-内酰胺酶与肺炎克雷伯菌细胞侵袭增加及菌毛黏附素表达有关。

Extended-spectrum beta-lactamase production is associated with an increase in cell invasion and expression of fimbrial adhesins in Klebsiella pneumoniae.

作者信息

Sahly H, Navon-Venezia S, Roesler L, Hay A, Carmeli Y, Podschun R, Hennequin C, Forestier C, Ofek I

机构信息

Institute for Infection Medicine, Faculty of Medicine, University of Kiel, Kiel, Germany.

出版信息

Antimicrob Agents Chemother. 2008 Sep;52(9):3029-34. doi: 10.1128/AAC.00010-08. Epub 2008 Jun 23.

Abstract

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.

摘要

产超广谱β-内酰胺酶(ESBL)的肺炎克雷伯菌菌株被认为比不产ESBL的菌株具有更高的致病潜力。微生物对宿主细胞的黏附和侵袭是感染过程中的关键步骤,因此我们检测了58株产ESBL和152株不产ESBL的肺炎克雷伯菌分离株1型和3型菌毛黏附素的表达情况,以及它们侵袭回盲部和膀胱上皮细胞的能力。分别通过评估豚鼠红细胞的甘露糖敏感血凝反应和牛红细胞的甘露糖抗性血凝反应来确定菌株表达1型和3型菌毛的能力。分别通过酶联免疫吸附测定和亚胺培南杀菌试验检测细菌对上皮细胞的黏附和侵袭情况。产ESBL和不产ESBL的菌株对上皮细胞的黏附没有显著差异(P>0.05)。相比之下,产ESBL的菌株中能够侵袭(相对侵袭率>5%)回盲部和膀胱上皮细胞的比例(分别为81%,n = 47/58和27.6%,n = 16/58)显著高于不产ESBL的菌株(分别为61%,n = 93/152和10%,n = 15/152)(P = 0.0084,优势比[OR]=2.711,95%置信区间[CI]=1.302至5.643;P = 0.0021,OR = 4.79,95%CI = 1.587至7.627)。产ESBL菌株的平均侵袭率(分别为5.5%±2.8%和3.3%±2.7%)显著高于不产ESBL的菌株(分别为2.9%±2.6%和1.8%±2%)(P<0.0001)。同样,同时表达两种菌毛黏附素的产ESBL菌株的比例(79.3%;n = 46/58)显著高于不产ESBL的菌株(61.8%;n = 94/152)(P = 0.0214;OR = 2.365;95%CI = 1.157至4.834)。获得携带SHV - 12编码质粒后,两个接合子开始产生3型菌毛,而1型菌毛的表达未受影响。获得ESBL质粒似乎上调了一个或多个基因的表型表达,导致更强的侵袭能力。

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