The mechanism of heterogeneous beta-lactam resistance in MRSA: key role of the stringent stress response.
The mechanism of heterogeneous beta-lactam resistance in MRSA: key role of the stringent stress response.
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DOI：
10.1371/journal.pone.0082814
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tomasz A
中科院分区：
文献类型：
--
作者：
Kim C;Mwangi M;Chung M;Milheiriço C;de Lencastre H;Tomasz A
所有耐甲氧西林金黄色葡萄球菌 (MRSA) 菌株都携带获得性遗传决定簇 - mecA 或 mecC - 编码低亲和力青霉素结合蛋白 - PBP2A 或 PBP2A' - 在高浓度 β-内酰胺抗生素存在的情况下可以继续催化肽聚糖转肽作用，从而抑制通常参与葡萄球菌细胞壁合成的天然 PBP肽聚糖。与所有 MRSA 菌株所携带的这种常见遗传和生化机制相反，β-内酰胺抗生素耐药性水平显示出非常广泛的菌株变异，但其机制仍知之甚少。绝大多数 MRSA 菌株产生独特的异质表型，其中绝大多数细菌表现出非常差的耐药性，通常接近易感金黄色葡萄球菌菌株的 MIC 值。然而，这种异质抗性 MRSA 菌株的培养物还含有具有极高 β-内酰胺 MIC 值的细菌亚群，并且此类菌株中高度抗性细胞的抗性水平和频率是特定 MRSA 克隆的特征。在本次通讯中描述的研究中，我们使用了多种实验模型来了解异质β-内酰胺耐药的机制。甲氧西林敏感金黄色葡萄球菌 (MSSA) 在实验室中以质粒或染色体 SCCmec 盒的形式接受 mecA 决定簇，产生异质抗性培养物，这些模型中出现的高度抗性亚群的 PBP2A 水平增加，并且由诱导严格应激反应的细菌组成。如果生长培养基含有严格应激反应的诱导剂，则MRSA临床分离株的每个主要异质抗性克隆都可以转化为表达高水平和同质的抗性。
All methicillin resistant S. aureus (MRSA) strains carry an acquired genetic determinant – mecA or mecC - which encode for a low affinity penicillin binding protein –PBP2A or PBP2A′ – that can continue the catalysis of peptidoglycan transpeptidation in the presence of high concentrations of beta-lactam antibiotics which would inhibit the native PBPs normally involved with the synthesis of staphylococcal cell wall peptidoglycan. In contrast to this common genetic and biochemical mechanism carried by all MRSA strains, the level of beta-lactam antibiotic resistance shows a very wide strain to strain variation, the mechanism of which has remained poorly understood. The overwhelming majority of MRSA strains produce a unique – heterogeneous – phenotype in which the great majority of the bacteria exhibit very poor resistance often close to the MIC value of susceptible S. aureus strains. However, cultures of such heterogeneously resistant MRSA strains also contain subpopulations of bacteria with extremely high beta-lactam MIC values and the resistance level and frequency of the highly resistant cells in such strain is a characteristic of the particular MRSA clone. In the study described in this communication, we used a variety of experimental models to understand the mechanism of heterogeneous beta-lactam resistance. Methicillin-susceptible S. aureus (MSSA) that received the mecA determinant in the laboratory either on a plasmid or in the form of a chromosomal SCCmec cassette, generated heterogeneously resistant cultures and the highly resistant subpopulations that emerged in these models had increased levels of PBP2A and were composed of bacteria in which the stringent stress response was induced. Each of the major heterogeneously resistant clones of MRSA clinical isolates could be converted to express high level and homogeneous resistance if the growth medium contained an inducer of the stringent stress response.
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影响因子：
3.7
作者：
NOVICK, R
通讯作者：
NOVICK, R
DOI：
10.1089/mdr.2000.6.1
发表时间：
2000-03-01
期刊：
MICROBIAL DRUG RESISTANCE-MECHANISMS EPIDEMIOLOGY AND DISEASE
影响因子：
--
作者：
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通讯作者：
Westh, H
影响因子：
3.2
作者：
Wu, SW;de Lancastre, H;Tomasz, A
通讯作者：
Tomasz, A
影响因子：
2.4
作者：
Crosse, AM;Greenway, DLA;England, RR
通讯作者：
England, RR
影响因子：
6.7
作者：
Geiger T;Francois P;Liebeke M;Fraunholz M;Goerke C;Krismer B;Schrenzel J;Lalk M;Wolz C
通讯作者：
Wolz C