Mikami Yuzuru
Chiba University.
Nihon Ishinkin Gakkai Zasshi. 2010;51(4):179-92. doi: 10.3314/jjmm.51.179.
The present taxonomic situation of pathogenic actinomycetes including Nocardia was clarified, and the impact of genomic sequence information of Nocardia farcinica IFM 10152 on taxonomic work is introduced. The number of cases of nocardiosis is on the rise along with the increasing number of immunocompromised patients in Japan. From 1999 to 2007, 718 strains of pathogenic actinomycetes were received for identification by Medical Mycology Research Center (MMRC), Chiba University. About 75% of these were classified into Nocardia, major species being N. farcinica, N. nova, and N. brasiliensis. Among the strains classified as Nocardia species, there were some unclassifiable strains and taxonomic studies on these led to the proposal of more than 18 new species, resulting in more than 1/4 of all Nocardia species having been proposed by our group. Recently a new Nocardia species, Nocardia mikamii was proposed by American researchers. A new phylogenetic analysis method using gryB and secA1 genes was proposed for the Nocardia and Gordonia strains.Our whole genome analysis of N. farcinica suggests that the bacterium has unique and characteristic gene profiles, and also suggests that N. farcinica is similar to Mycobacterium tuberculosis. N. farcinica also has siderophore (nocobactin) and mce genes which are similar to mycobactin (siderophore) of M. tuberculosis as virulence factors. Nocardia strains were found to be producers of new secondary metabolites including antifungal, antitumor and immunosuppressive activities.We reported novel antibiotic resistance mechanisms such as ribosylation, glucosylation, phosphorylation and degradation of rifampicin, phosphorylation of aminoglycosides, and glucosylation of macrolide antibiotics. Among rifampicin inactivation mechanisms, ribosylation was found to be through the Arr enzyme that catalyzes ADP-ribosylation of rifampicin in a fast-growing Mycobacterium smegmatis. This unique mechanism has also been reported as an antibiotic resistant mechanism in pathogenic Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii.Our cooperative work on the elucidation of high-level resistance to the aminoglycoside antibiotic amikacin in N. farcinica with a research group from CDC, USA, revealed the presence of homozygous mutations in the 16R rRNA genes which are responsible for high-level aminoglycoside antibiotic resistance.
阐明了包括诺卡氏菌属在内的致病性放线菌的当前分类学状况，并介绍了豚鼠耳炎诺卡氏菌IFM 10152的基因组序列信息对分类学工作的影响。在日本，随着免疫功能低下患者数量的增加，诺卡氏菌病的病例数也在上升。1999年至2007年，千叶大学医学真菌研究中心（MMRC）接收了718株致病性放线菌进行鉴定。其中约75%被归类为诺卡氏菌属，主要菌种为豚鼠耳炎诺卡氏菌、新星诺卡氏菌和巴西诺卡氏菌。在被归类为诺卡氏菌属的菌株中，有一些无法分类的菌株，对这些菌株的分类学研究导致了18个以上新物种的提出，我们团队提出的新物种占所有诺卡氏菌属物种的1/4以上。最近，美国研究人员提出了一种新的诺卡氏菌属物种——御殿场诺卡氏菌。针对诺卡氏菌属和戈登氏菌属菌株，提出了一种使用gryB和secA1基因的新系统发育分析方法。我们对豚鼠耳炎诺卡氏菌的全基因组分析表明，该细菌具有独特的基因图谱，也表明豚鼠耳炎诺卡氏菌与结核分枝杆菌相似。豚鼠耳炎诺卡氏菌还具有铁载体（诺卡菌素）和mce基因，这些基因作为毒力因子与结核分枝杆菌的分枝菌素（铁载体）相似。发现诺卡氏菌属菌株是包括具有抗真菌、抗肿瘤和免疫抑制活性在内的新次级代谢产物的生产者。我们报道了新的抗生素耐药机制，如利福平的核糖基化、糖基化、磷酸化和降解、氨基糖苷类的磷酸化以及大环内酯类抗生素的糖基化。在利福平失活机制中，发现核糖基化是通过Arr酶催化快速生长的耻垢分枝杆菌中利福平的ADP-核糖基化。这种独特的机制也已在致病性大肠杆菌、铜绿假单胞菌、肺炎克雷伯菌和鲍曼不动杆菌中作为抗生素耐药机制被报道。我们与美国疾病控制与预防中心的一个研究小组合作，对豚鼠耳炎诺卡氏菌对氨基糖苷类抗生素阿米卡星的高水平耐药性进行了研究，结果显示16R rRNA基因中存在纯合突变，这些突变导致了对氨基糖苷类抗生素的高水平耐药性。
