ZOOCIN A AND ITS ASSOCIATED IMMUNITY FACTOR

ZOOCIN A 及其相关免疫因子

• 批准号: 6226478
• 负责人: GARY L SLOAN
• 金额: $ 14.3万
• 依托单位: UNIVERSITY OF ALABAMA IN TUSCALOOSA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6226478
• 关键词: Streptococcus; antibiotics; bacterial genetics; bacterial proteins; bacterial toxins; bacteriocin; immunity; microorganism metabolism; peptidoglycan

DESCRIPTION (Verbatim from Applicant's Abstract): The long-term goal of this research is to understand the control and transfer of information that allows some bacteria to produce toxic products to which they are not intrinsically resistant. The model systems being studied are lysostaphin, a plasmid-encoded staphylolytic glycylglycine endopeptidase produced by Staphylococcus simulans biovar staphylolyticus, which hydrolyzes the polyglycine cross bridges in the cell wall peptidoglycans of other staphylococci, and zoocin A, a chromosomally encoded streptococcolytic enzyme of unknown mechanism of action that is produced by Streptococcus equi subsp. zooepidemicus 4881. A comparison of the sequences of the genes for lysostaphin endopeptidase (end) and zoocin A (zooA) has revealed a high degree of similarity between these two enzymes; however, our preliminary investigations have revealed that zoocin A is most likely not simply an endopeptidase that hydrolyzes peptidoglycan cross bridges in susceptible streptococci. Both organisms carry resistance genes that also have a high degree of similarity (designated epr, for lysostaphin endopeptidase resistance and zif, for zoocin A immunity factor) immediately adjacent to the enzyme genes and oriented in the opposite direction to them. Both epr and zif have a high degree of similarity to femAB (factor essential for methicillin resistance) in staphylococci. The gene products for epr and femAB are known to be involved in the synthesis of cross bridges in the peptidoglycans of staphylococci; Epr specifies for the insertion of serines in these peptides whereas FemA and FemB specify for the insertion of glycines. Even though Zif is very similar to Epr, FemA, and FemB, our preliminary investigations have revealed that it is not involved in the biosynthesis of cross bridges. In addition, both end/epr and zooA/zif are bracketed by what appear to be transposable elements, suggesting that there may have been a horizontal transfer of DNA fragments containing these genes at some point in time. The specific aims of the proposed project are 1) to identify the site of action of zoocin A on the peptidoglycans of susceptible streptococci; 2) to identify the precise change made in streptococcal cell wall peptidoglycans by Zif and the cellular location of this protein; and 3) to determine if end/epr or zooA/zif can be transferred to other gram-positive organisms by natural mechanisms for genetic transfer.

描述（来自申请人摘要的逐字）：本发明的长期目标是： 研究的目的是了解信息的控制和传递， 一些细菌产生有毒的产品，他们不是本质上 抵抗正在研究的模型系统是溶葡萄球菌酶， 由模拟葡萄球菌产生的葡萄糖分解甘氨酰甘氨酸内肽酶 biovar staphylolyticus，其水解聚甘氨酸跨桥， 其他葡萄球菌的细胞壁肽聚糖，以及zoocin A，一种染色体 编码的作用机制未知的链球菌溶解酶， 由马链球菌亚种（Streptococcus equi subsp.）4881.的比较 溶葡萄球菌酶内肽酶（end）和zooocin A（zooA）的基因序列 已经揭示了这两种酶之间的高度相似性;然而， 我们的初步调查显示，zoocin A很可能不是 仅仅是水解肽聚糖跨桥的内肽酶 易感链球菌这两种生物都携带有抗性基因， 高度的相似性（命名为EPR，用于溶葡萄球菌酶内肽酶 resistance和zif，用于zoocin A免疫因子）紧邻 酶基因，并以相反的方向定向。epr和zif 与femAB（甲氧西林必需因子）具有高度相似性 耐药性）。已知epr和femAB的基因产物 参与肽聚糖中交叉桥的合成 Epr指定在这些肽中插入丝氨酸 而FemA和FemB指定插入甘氨酸。尽管Zif 与Epr，FemA和FemB非常相似，我们的初步调查 表明它不参与横桥的生物合成。在 此外，end/epr和zooA/zif都被似乎是 转座因子，这表明可能有一个水平 在某个时间点转移含有这些基因的DNA片段。的 拟议项目的具体目标是：（1）确定 Zoocin A对敏感链球菌肽聚糖的作用; 2）鉴定 通过Zif和蛋白质在链球菌细胞壁肽聚糖中的精确改变， 该蛋白质的细胞定位;和3）确定end/epr或zooA/zif 可以通过自然机制转移到其他革兰氏阳性生物体， 基因转移