Methicillin-resistance in Staphylococcus aureus is not affected by the overexpression in trans of the mecA gene repressor: a surprising observation.
Methicillin-resistance in Staphylococcus aureus is not affected by the overexpression in trans of the mecA gene repressor: a surprising observation.
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DOI：
10.1371/journal.pone.0023287
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
de Lencastre H
中科院分区：
文献类型：
--
作者：
Oliveira DC;de Lencastre H
耐甲氧西林金黄色葡萄球菌(MRSA)对几乎所有β-内酰胺类抗生素具有内在的交叉耐药性。MRSA表型的核心决定因素是mecA基因，其转录调控可能由一个抑制子(MecI)和一个传感器/诱导子(MecR1)介导。MecI-mecR1介导的mecA诱导过程需要几个小时，使菌株在存在耐药基因的情况下仍表现为敏感。因此，有人提出，许多当代临床分离株对β-内酰胺类药物的完全耐药需要一个非功能性的mecI-mecR1调控系统。MecA基因嵌入了一个大的染色体盒(SCCmec元件)，已经描述了几种结构类型。一些流行的耐甲氧西林金黄色葡萄球菌克隆通常表达完全的β-内酰胺耐药，携带含有完整的mecI-mecR1基因座的SCCmec元件(例如SCCmec类型II和III型)。我们已经解决了这一明显的矛盾，首先对不同SCCmec类型的MRSA原型菌株的mecI编码区和mecA启动子序列进行了测序。在所有测试的SCCmec III型菌株中都检测到mecI内的保守无义突变，推测这可能是导致MecI蛋白不起作用的原因，因此解释了完全耐药的表型。在SCCmec II型菌株中未发现保守突变。接下来，我们用过量表达野生型mecI拷贝的重组质粒转化了一组MRSA流行株原型。令人惊讶的是，对于绝大多数菌株来说，β-内酰胺类耐药的表型表达没有检测到明显的变化。这些发现得到了证实和进一步的探索，挑战了目前公认的mecA转录调控机制。我们的观察表明，参与mecA基因转录控制的尚不确定的其他决定因素的存在，并指出当代MRSA菌株中mecA调控机制的修订。
Methicillin-resistant Staphylococcus aureus (MRSA) is intrinsically cross-resistant to virtually all β-lactam antibiotics. The central determinant for the MRSA phenotype is the mecA gene, whose transcriptional control may be mediated by a repressor (mecI) and a sensor/inducer (mecR1). The mecI-mecR1-mediated induction of mecA takes several hours rendering the strains phenotypically susceptible in spite of the presence of the resistance gene. Therefore, it has been proposed that the full resistance to β-lactams observed in many contemporary clinical MRSA strains requires a non-functional mecI-mecR1 regulatory system. The mecA gene is embedded in a large chromosomal cassette (the SCCmec element) for which several structural types have been described. Some epidemic MRSA clones, typically expressing full β-lactam resistance, carry SCCmec elements that contain an intact mecI-mecR1 locus (e.g. SCCmec types II and III). We have addressed this apparent contradiction by first sequencing the mecI coding region and mecA promoter sequences in a collection of prototype MRSA strains characterized by different SCCmec types. A conserved non-sense mutation within mecI was detected in all SCCmec type III strains tested, presumably responsible for a non-functional truncated MecI protein and, therefore, explaining the full resistance phenotype. In SCCmec type II strains no conserved mutations were found. We next transformed a collection of prototype MRSA epidemic strains with a recombinant plasmid overexpressing a wild-type copy of mecI. Surprisingly, for the great majority of the strains no significant alterations in the phenotypic expression of β-lactam resistance could be detected. These findings were confirmed and further explored, challenging the currently accepted mechanism of mecA transcriptional control. Our observations suggest the existence of yet unidentified additional determinants involved in the transcriptional control of mecA gene and point to a revision of the mecA regulatory mechanism in contemporary MRSA strains.
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影响因子：
4.9
作者：
ARCHER, GL;NIEMEYER, DM;PUCCI, MJ
通讯作者：
PUCCI, MJ
影响因子：
4.9
作者：
HARTMAN, B;TOMASZ, A
通讯作者：
TOMASZ, A
影响因子：
4.9
作者：
Kobayashi, N;Taniguchi, K;Urasawa, S
通讯作者：
Urasawa, S
DOI：
10.1126/science.1182395
发表时间：
2010-01-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Harris SR;Feil EJ;Holden MT;Quail MA;Nickerson EK;Chantratita N;Gardete S;Tavares A;Day N;Lindsay JA;Edgeworth JD;de Lencastre H;Parkhill J;Peacock SJ;Bentley SD
通讯作者：
Bentley SD
影响因子：
2.7
作者：
Jett, BD;Hatter, KL;Gilmore, MS
通讯作者：
Gilmore, MS