ADAPTIVE ACIDIFICATION TOLERANCE RESPONSE OF SALMONELLA-TYPHIMURIUM
ADAPTIVE ACIDIFICATION TOLERANCE RESPONSE OF SALMONELLA-TYPHIMURIUM
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DOI：
10.1128/jb.172.2.771-778.1990
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发表时间：
1990-02-01
影响因子：
3.2
通讯作者：
HALL, HK
中科院分区：
文献类型：
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作者：
FOSTER, JW;HALL, HK
鼠伤寒沙门氏菌在其生命周期中会遇到各种各样的环境。环境中的一个会大幅波动的因素是酸碱度（pH）。在自然界中，鼠伤寒沙门氏菌能够经历并在从池塘水到吞噬溶酶体等不同生态位中出现的剧烈酸性胁迫下存活。然而，在体外该菌对酸非常敏感。为了解释这种细菌在自然环境中如何在酸性条件下存活，对鼠伤寒沙门氏菌形成耐酸能力的适应性进行了测试。对数生长期的细胞（pH值为7.6）转移到弱酸性环境（pH值为5.8）中经过一次倍增作为适应性过程，其对随后的强酸挑战（pH值为3.3）的抵抗力比直接从pH值7.6转移到3.3的未适应细胞高100到1000倍。这种耐酸化反应需要蛋白质合成，并且似乎是一种针对酸的特异性防御机制。未发现对过氧化氢、SOS反应或热休克有交叉保护作用。对酸调节多肽进行的双向聚丙烯酰胺凝胶电泳分析显示有18种蛋白质表达发生改变，其中6种被抑制，而12种被弱酸性变化诱导。一种无毒力的phoP突变体对酸的敏感性比其有毒力的phoP⁺亲本高1000倍，这表明耐酸性和毒力之间存在相关性。还发现依赖镁离子的质子转运ATP酶在耐酸性方面起着重要作用。缺乏这种活性的突变体（unc）无法产生耐酸反应，并且对酸极其敏感。与这些对酸敏感的突变体相反，在长时间暴露于酸之后从野生型LT2中分离出一种组成型耐酸突变体（atr）。这种突变体过度表达了几种耐酸化反应多肽。所提供的数据揭示了一个重要的酸化防御调节子，它对在生物有害环境中的生存具有广泛的意义。
Salmonella typhimurium can encounter a wide variety of environments during its life cycle. One component of the environment which will fluctuate widely is pH. In nature, S. typhimurium can experience and survive dramatic acid stresses that occur in diverse ecological niches ranging from pond water to phagolysosomes. However, in vitro the organism is very sensitive to acid. To provide an explanation for how this organism survives acid in natural environments, the adaptive ability of S. typhimurium to become acid tolerant was tested. Logarithmically grown cells (pH 7.6) shifted to mild acid (pH 5.8) for one doubling as an adaptive procedure were 100 to 1,000 times more resistant to subsequent strong acid challenge (pH 3.3) than were unadapted cells shifted directly from pH 7.6 to 3.3. This acidification tolerance response required protein synthesis and appears to be a specific defense mechanism for acid. No cross protection was noted for hydrogen peroxide, SOS, or heat shock. Two-dimensional polyacrylamide gel electrophoretic analysis of acid-regulated polypeptides revealed 18 proteins with altered expression, 6 of which were repressed while 12 were induced by mild acid shifts. An avirulent phoP mutant was 1,000-fold more sensitive to acid than its virulent phoP+ parent, suggesting a correlation between acid tolerance and virulence. The Mg2+-dependent proton-translocating ATPase was also found to play an important role in acid tolerance. Mutants (unc) lacking this activity were unable to mount an acid tolerance response and were extremely acid sensitive. In contrast to these acid-sensitive mutants, a constitutively acid-tolerant mutant (atr) was isolated from wild-type LT2 after prolonged acid exposure. This mutant overexpressed several acidification tolerance response polypeptides. The data presented reveal an important acidification defense modulon with broad significance toward survival in biologically hostile environments.