Characterization of novel Mycobacterium tuberculosis and Mycobacterium smegmatis mutants hypersusceptible to β-lactam antibiotics
Characterization of novel Mycobacterium tuberculosis and Mycobacterium smegmatis mutants hypersusceptible to β-lactam antibiotics
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DOI：
10.1128/jb.187.6.1892-1900.2005
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发表时间：
2005-03-01
影响因子：
3.2
通讯作者：
Pavelka, MS Jr
中科院分区：
文献类型：
--
作者：
Flores, AR;Parsons, LM;Pavelka, MS Jr
我们的实验室之前分别构建了结核分枝杆菌和耻垢分枝杆菌的突变体，其主要的β -内酰胺酶BlaC和BlaS基因缺失，并表明突变体对大多数p -内酰胺类抗生素，特别是青霉素的敏感性增加。然而，突变体对某些青霉素仍有基础水平的耐药，并且突变体对某些基于头孢菌素的β -内酰胺类药物的敏感性与野生型基本相同。我们假设，对β -内酰胺类抗生素敏感的其他突变体（来源于β -内酰胺酶缺失突变体）的特征可能揭示与β -内酰胺耐药、肽聚糖组装和细胞包膜生理学等其他机制有关的新基因。我们在这里报道了9个β -内酰胺类抗生素敏感转座子突变体的分离和特性，其中两个突变体插入已知参与肽聚糖生物合成的基因（pon，A2和dapB）；其他七个突变体有影响新基因的插入。这些基因可分为三类：参与肽聚糖生物合成、细胞分裂和其他细胞包膜过程的基因。两个肽聚糖生物合成基因（ponA2和pbpX）可能编码β -内酰胺耐药酶，这些酶被认为参与了分枝杆菌肽聚糖中不寻常的二氨基甲酰基键的合成。
Our laboratory previously constructed mutants of Mycobacterium tuberculosis and Mycobacterium smegmatis with deletions in the genes for their major beta-lactamases, BlaC and BlaS, respectively, and showed that the mutants have increased susceptibilities to most P-lactam antibiotics, particularly the penicillins. However, there is still a basal level of resistance in the mutants to certain penicillins, and the susceptibilities of the mutants to some cephalosporin-based beta-lactams are essentially the same as those of the wild types. We hypothesized that characterizing additional mutants (derived from beta-lactamase deletion mutants) that are hypersusceptible to beta-lactam antibiotics might reveal novel genes involved with other mechanisms of beta-lactam resistance, peptidoglycan assembly, and cell envelope physiology. We report here the isolation and characterization of nine beta-lactam antibiotic-hypersusceptible transposon mutants, two of which have insertions in genes known to be involved with peptidoglycan biosynthesis (pon,A2 and dapB); the other seven mutants have insertions which affect novel genes. These genes can be classified into three groups: those involved with peptidoglycan biosynthesis, cell division, and other cell envelope processes. Two of the peptidoglycan-biosynthetic genes (ponA2 and pbpX) may encode beta-lactam antibiotic-resistant enzymes proposed to be involved with the synthesis of the unusual diaminopimelyl linkages within the mycobacteriall peptidoglycan.