Cellular impermeability and uptake of biocides and antibiotics in Gram-positive bacteria and mycobacteria
Cellular impermeability and uptake of biocides and antibiotics in Gram-positive bacteria and mycobacteria
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DOI：
10.1046/j.1365-2672.92.5s1.7.x
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发表时间：
2002-01-01
影响因子：
4
通讯作者：
Lambert, PA
中科院分区：
文献类型：
--
作者：
Lambert, PA
革兰氏阳性菌具有可渗透的细胞壁，通常不会限制抗菌剂的渗透。然而，由于限制性渗透可能发生耐药性，如万古霉素中间耐药金黄色葡萄球菌菌株（VISA）所示，其产生显著增厚的细胞壁。这些菌株的变化包括肽聚糖中非酰胺化谷氨酰胺残基的量增加，并表明耐药机制涉及万古霉素在增厚的细胞壁中的“亲和捕获”。VISA菌株具有降低的倍增时间、对溶葡萄球菌酶的较低敏感性和降低的自溶活性，这可能反映了壁和膜磷壁酸的D-丙氨酰酯含量的变化。分枝杆菌细胞壁具有高脂质含量，其被认为是抗微生物剂渗透的主要屏障。相对疏水性的抗生素如利福平和氟喹诺酮类可能能够通过扩散穿过由长链长度分枝菌酸和糖脂组成的疏水双层而穿过细胞壁。亲水性抗生素和营养物质不能通过这一层扩散，并被认为使用孔蛋白通道，这在许多分枝杆菌中已有报道。脂质双层中孔蛋白的出现支持分枝杆菌壁具有类似于革兰氏阴性菌的外膜的观点。然而，分枝杆菌孔蛋白比革兰氏阴性菌外膜中的孔蛋白少得多，并且仅允许低速率的小亲水性营养素和抗生素的摄取。
Gram-positive bacteria possess a permeable cell wall that usually does not restrict the penetration of antimicrobials. However, resistance due to restricted penetration can occur, as illustrated by vancomycin-intermediate resistant Staphylococcus aureus strains (VISA) which produce a markedly thickened cell wall. Alterations in these strains include increased amounts of nonamidated glutamine residues in the peptidoglycan and it is suggested that the resistance mechanism involves 'affinity trapping' of vancomycin in the thickened cell wall. VISA strains have reduced doubling times, lower sensitivity to lysostaphin and reduced autolytic activity, which may reflect changes in the D-alanyl ester content of the wall and membrane teichoic acids. Mycobacterial cell walls have a high lipid content, which is assumed to act as a major barrier to the penetration of antimicrobial agents. Relatively hydrophobic antibiotics such as rifampicin and fluoroquinolones may be able to cross the cell wall by diffusion through the hydrophobic bilayer composed of long chain length mycolic acids and glycolipids. Hydrophilic antibiotics and nutrients cannot diffuse across this layer and are thought to use porin channels which have been reported in many species of mycobacteria. The occurrence of porins in a lipid bilayer supports the view that the mycobacterial wall has an outer membrane analogous to that of Gram-negative bacteria. However, mycobacterial porins are much less abundant than in the Gram-negative outer membrane and allow only low rates of uptake for small hydrophilic nutrients and antibiotics.