EXPRESSION AND FUNCTION OF BACTERIAL CELL SURFACE COMPONENTS

细菌病原体必须能够在其宿主中侵入和繁殖。 宿主防御，如血清杀伤和吞噬作用，成功地 抵抗入侵者，在感染建立的地方， 抗生素的施用可以为宿主提供额外的时间， 消灭入侵的病原体。这些研究集中在细胞如何 病原菌表面成分在抵抗宿主中的作用 防御机制和抗生素 大肠埃希菌、鼠伤寒沙门氏菌和其他革兰氏阴性菌 细菌在表型上对各种不相关的 在含有0.5~10 mM对乙酰氨基酚的培养基中生长时， 增加的抗生素抗性是由于表达减少 孔蛋白这种效应与所见的相似，如果不是相同的话 当这些细胞在水杨酸钠中生长时。 56个革兰氏阴性菌株，作为人类病原体分离，生长在 水杨酸钠存在及其对四种药物中每一种的敏感性 检测的抗生素[头孢西丁、环丙沙星、诺氟沙星和四环素 所有菌株的最小抑菌浓度均显示出至少4倍的增加， 至少一种抗生素的浓度[MIC]和大多数显示 研究的所有四种抗生素的MIC均显著增加。的56 研究的菌株包括不动杆菌属，柠檬酸杆菌属， 肠杆菌属、埃希氏菌属、克雷伯氏菌属、变形杆菌属。 几个遗传基因座参与调节基因的表达， 大肠杆菌外膜孔蛋白。表达调控 外膜中Omp F的表达，各种lacZ+融合菌株 在水杨酸盐存在或不存在的情况下生长。水杨酸的作用 对ompF表达的影响与培养基的渗透压无关。 它是上位性的envZ 3和ompR 331 β调节突变。 像水杨酸一样，这些突变产生高组成水平的 micF转录和伴随的低水平OmpF孔蛋白表达。 这些结果表明，水杨酸盐的生长严重降低了 通过增强micF的表达来翻译ompF。在这 在这方面，sal/-生长的细胞类似于marA或tolC突变株， micF含量高OmpF含量低 博士Foulds被详细介绍给国家疫苗计划办公室， [2015年3月15日-9月30日]，他担任 该项目的分析师和科学顾问。

A bacterial pathogen must be able to invade and multiply in its host. Host defenses, such as serum-killing and phagocytosis, successfully oppose the invader and where an infection becomes established, administration of antibiotics may provide additional time for the host to eliminate invading pathogen. These studies focus on the how the cell surface components of pathogenic bacteria function in resistance to host defense mechanisms and antibiotics. Escherichia coli, Salmonella typhimurium, and other Gram-negative bacteria become phenotypically resistant to a variety of unrelated antibiotics when grown in media containing 0.5~10 mM acetaminophen. The increased antibiotic resistance is due to the decreased expression of porin protein. This effect is similar, if not identical, to that seen when these same cells are grown in sodium salicylate. 56 Gram-negative strains, isolated as human pathogens, were grown in the presence of sodium salicylate and their sensitivity to each of four antibiotics tested [Cefoxitin, Ciprofloxacin, Norfloxacin, and Tetracycline All strains showed a minimally 4-fold increase in the minimal inhibitory concentration [MIC] of at least one antibiotic and most showed significant increase in the MIC of all four antibiotics studied. The 56 strains studied included species of Acinetobacter, Citrobacter, Enterobacter, Escherichia, Klebsiella, Proteus. Several genetic loci are involved in the regulation of the expression of the Escherichia coli outer membrane porins. The regulation of expression of Omp F in the outer membrane, various lacZ+ fusion strains were grown in the presence or absence of salicylate. The effect of salicylate on ompF expression was independent of the osmolarity of the medium. It was epistatic to the envZ3 and ompR331 osmoregulatory mutations. Like salicylate, these mutations, engender high constitutive levels of micF transcription and concomitant low levels of OmpF porin expression. These results showed that growth in salicylate severely decreases the translation of ompF by enhancing the expression of micF. In this respect, sal/-grown cells resemble marA or tolC mutant strains that have high levels of micF and low levels of OmpF. Dr. Foulds was detailed to the National Vaccine Program Office for part of the year [March 15-September 30] where he served as a policy analyst and scientific advisor to the program.