Cross-Resistance to Lincosamides, Streptogramins A, and Pleuromutilins Due to the lsa(C) Gene in Streptococcus agalactiae UCN70
Cross-Resistance to Lincosamides, Streptogramins A, and Pleuromutilins Due to the lsa(C) Gene in Streptococcus agalactiae UCN70
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DOI：
10.1128/aac.01068-10
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发表时间：
2011-04-01
影响因子：
4.9
通讯作者：
Cattoir, Vincent
中科院分区：
文献类型：
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作者：
Malbruny, Brigitte;Werno, Anja M.;Cattoir, Vincent
从新西兰获得的阴道拭子中分离的无乳链球菌UCN 70对林可酰胺和链阳性菌素A（LSA表型）以及泰妙菌素（截短侧耳素）具有耐药性。通过全基因组测序，我们鉴定了一个5，224-bp的染色体额外元件，其包含一个1，479-bp的开放阅读框，编码与Lsa（A）45%相同的ABC蛋白（492个氨基酸），Lsa（A）是一种与粪肠球菌内在LSA抗性相关的蛋白。将该基因命名为lsa（C），并在S.克隆后无乳BM 132导致林可霉素MIC增加（0.06 - 4 μ g/ml），克林霉素（0.03至2 μ g/ml），达福普汀（2至> 32 μ g/ml），以及泰妙菌素（0.12至32 μ g/ml），而红霉素的MIC无变化06 μ g/ml）、阿奇霉素（0.03 μ g/ml）、螺旋霉素（0.25 μ g/ml）、泰利霉素（0.03 μ g/ml）和奎奴普汀（8 μ g/ml）。基于对林可酰胺、链阳性菌素A和截短侧耳素的交叉耐药性，将该表型重命名为LSAP表型。该基因也在其他17个S.新西兰无乳链球菌临床分离株表现出相同的LSAP表型，而敏感的S.无乳菌株。有趣的是，这个额外的元件被一个7-bp的靶位点（ATTAGAA）的重复包围，这表明这个结构可能是一个移动的遗传元件。总之，我们鉴定了一个新的基因lsa（C），该基因负责S.无乳。对抗性的生化基础的剖析以及lsa（C）的体外动员的证明仍有待进行。
Streptococcus agalactiae UCN70, isolated from a vaginal swab obtained in New Zealand, is resistant to lincosamides and streptogramins A (LSA phenotype) and also to tiamulin (a pleuromutilin). By whole-genome sequencing, we identified a 5,224-bp chromosomal extra-element that comprised a 1,479-bp open reading frame coding for an ABC protein (492 amino acids) 45% identical to Lsa(A), a protein related to intrinsic LSA resistance in Enterococcus faecalis. Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 mu g/ml), clindamycin (0.03 to 2 mu g/ml), dalfopristin (2 to > 32 mu g/ml), and tiamulin (0.12 to 32 mu g/ml), whereas no change in MICs of erythromycin (0.06 mu g/ml), azithromycin (0.03 mu g/ml), spiramycin (0.25 mu g/ml), telithromycin (0.03 mu g/ml), and quinupristin (8 mu g/ml) was observed. The phenotype was renamed the LSAP phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins. This gene was also identified in similar genetic environments in 17 other S. agalactiae clinical isolates from New Zealand exhibiting the same LSAP phenotype, whereas it was absent in susceptible S. agalactiae strains. Interestingly, this extra-element was bracketed by a 7-bp duplication of a target site (ATTAGAA), suggesting that this structure was likely a mobile genetic element. In conclusion, we identified a novel gene, lsa(C), responsible for the acquired LSAP resistance phenotype in S. agalactiae. Dissection of the biochemical basis of resistance, as well as demonstration of in vitro mobilization of lsa(C), remains to be performed.