Metronidazole Resistance in Prevotella spp. and Description of a New nim Gene in Prevotella baroniae

Metronidazole Resistance in Prevotella spp. and Description of a New nim Gene in Prevotella baroniae
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DOI:
10.1128/aac.01003-09
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发表时间:
2010-01-01
影响因子:
4.9
通讯作者:
Lozniewski, A.
Lozniewski, A.
中科院分区:
医学2区
文献类型:
--
作者:
Alauzet, C.;Mory, F.;Lozniewski, A.

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普雷沃菌属的非重复临床分离株。2003年至2006年期间,在法国的两个三级护理教学医院住院的患者中,研究了他们对甲硝唑的敏感性和nim基因的存在。在188个菌株测试,3个菌株表现出降低甲硝唑敏感性后48小时的孵育,而27个额外的菌株表现出异质性耐药后,长时间孵育,所有30个菌株是尼姆阴性。在其余158株分离株中,检测到7株nim阳性分离株。经16S rRNA基因序列分析,所有菌株均为巴氏普雷沃氏菌(Prevotella barcillae),并含有一个新的nim基因,命名为nimI。该单拷贝基因的染色体定位通过Southern杂交在所有临床分离株以及模式菌株巴氏毕赤酵母DSM 16972中得到证实。没有已知的相关插入序列元件检测到的nimI基因上游的任何nim阳性菌株通过PCR图谱。在长期暴露于甲硝唑后,可以在nimI阳性的普雷沃氏菌分离株(n = 6)以及nim阴性的普雷沃氏菌分离株(n = 6)中选择稳定的耐药亚群,而不管它们对这种抗生素的初始敏感性如何。本研究首次在巴氏疟原虫中发现了一个新的硝基咪唑抗性基因,该基因似乎是沉默的,可能是该物种固有的。此外,我们的研究结果强调了这样一个事实,即高水平的耐药性甲硝唑可能很容易诱导在两个尼姆阳性和尼姆阴性普雷沃菌属菌株。
Nonduplicate clinical isolates of Prevotella spp. recovered from patients hospitalized between 2003 and 2006 in two French tertiary-care teaching hospitals were investigated for their susceptibility to metronidazole and the presence of nim genes. Of the 188 strains tested, 3 isolates displayed reduced susceptibility to metronidazole after 48 h of incubation, while 27 additional isolates exhibited heterogeneous resistance after prolonged incubation; all 30 of the isolates were nim negative. Among the remaining 158 isolates, 7 nim-positive isolates were detected. All of these strains were identified as Prevotella baroniae by 16S rRNA gene sequence analysis and contained a new nim gene, named nimI, as determined by DNA sequence analysis. Chromosomal localization of this single-copy gene was demonstrated in all clinical isolates as well as in type strain P. baroniae DSM 16972 by using Southern hybridization. No known associated insertion sequence elements were detected upstream of the nimI gene in any of the nim-positive strains by PCR mapping. After prolonged exposure to metronidazole, stable resistant subpopulations could be selected in nimI-positive Prevotella isolates (n = 6) as well as in nim-negative Prevotella isolates (n = 6), irrespective of their initial susceptibility to this antibiotic. This study is the first description of a new nitroimidazole resistance gene in P. baroniae which seems to be silent and which might be intrinsic in this species. Moreover, our findings highlight the fact that high-level resistance to metronidazole may be easily induced in both nim-positive and nim-negative Prevotella sp. strains.