ZOOCIN A AND ITS ASSOCIATED IMMUNITY FACTOR

描述(逐字摘自申请者摘要)：该项目的长期目标 研究是为了了解信息的控制和传输，从而允许 一些细菌会产生它们本身并不存在的有毒产品 抵抗力强。正在研究的模型系统是溶葡萄球菌酶，一种质粒编码的 模拟葡萄球菌产生的溶葡萄球菌甘氨酰甘氨酸内肽酶 生物群金黄色葡萄球菌，它能降解体内的聚甘氨酸跨桥 其他葡萄球菌的细胞壁肽聚糖，以及染色体上的人祖菌素A 编码的作用机制未知的链球菌裂解酶，即 由马链球菌亚种产生。动物疫病4881号。两个版本之间的比较 溶葡萄球菌酶内肽酶(完)和人凝血素A(ZooA)基因序列 揭示了这两种酶之间的高度相似之处；然而， 我们的初步调查显示，动物素A很可能不是 仅仅是一种内肽酶，它能水解肽聚糖在体内的桥梁 敏感的链球菌。这两种生物携带的抗性基因也具有 高度相似(指定为EPR，用于溶葡萄球菌内肽酶 抵抗和ZIF，对于人A免疫因子)紧邻 酶基因与酶基因的方向相反。EPR和ZIF 与FemAB(甲氧西林必需因子)高度相似 耐药)。已知EPR和FemAB的基因产物 参与多肽多糖中交叉桥的合成 葡萄球菌；EPR规定在这些多肽中插入丝氨酸 而FEMA和FemB指定插入甘氨酸。即使ZIF是 与EPR、FEMA和FemB非常相似，我们的初步调查 揭示了它不参与交叉桥的生物合成。在……里面 此外，End/EPR和ZooA/ZIF都被似乎是 可转座的元素，表明可能存在水平的 在某个时间点转移包含这些基因的DNA片段。这个 拟议项目的具体目标是：1)确定行动地点 易感链球菌肽聚糖上的人凝集素A；2)鉴定 ZIF对链球菌胞壁肽聚糖的精确改变 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身上 基因转移。

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.