Department of Biology, Kenyon College, Gambier, Ohio, United States of America.
PLoS One. 2011 Apr 26;6(4):e18960. doi: 10.1371/journal.pone.0018960.
The TolC outer membrane channel is a key component of several multidrug resistance (MDR) efflux pumps driven by H(+) transport in Escherichia coli. While tolC expression is under the regulation of the EvgA-Gad acid resistance regulon, the role of TolC in growth at low pH and extreme-acid survival is unknown.
TolC was required for extreme-acid survival (pH 2) of strain W3110 grown aerobically to stationary phase. A tolC deletion decreased extreme-acid survival (acid resistance) of aerated pH 7.0-grown cells by 10(5)-fold and of pH 5.5-grown cells by 10-fold. The requirement was specific for acid resistance since a tolC defect had no effect on aerobic survival in extreme base (pH 10). TolC was required for expression of glutamate decarboxylase (GadA, GadB), a key component of glutamate-dependent acid resistance (Gad). TolC was also required for maximal exponential growth of E. coli K-12 W3110, in LBK medium buffered at pH 4.5-6.0, but not at pH 6.5-8.5. The TolC growth requirement in moderate acid was independent of Gad. TolC-associated pump components EmrB and MdtB contributed to survival in extreme acid (pH 2), but were not required for growth at pH 5. A mutant lacking the known TolC-associated efflux pumps (acrB, acrD, emrB, emrY, macB, mdtC, mdtF, acrEF) showed no growth defect at acidic pH and a relatively small decrease in extreme-acid survival when pre-grown at pH 5.5.
TolC and proton-driven MDR efflux pump components EmrB and MdtB contribute to E. coli survival in extreme acid and TolC is required for maximal growth rates below pH 6.5. The TolC enhancement of extreme-acid survival includes Gad induction, but TolC-dependent growth rates below pH 6.5 do not involve Gad. That MDR resistance can enhance growth and survival in acid is an important consideration for enteric organisms passing through the acidic stomach.
TolC 外膜通道是大肠杆菌中几种多药耐药（MDR）外排泵的关键组成部分，这些外排泵由 H+转运驱动。虽然 tolC 的表达受 EvgA-Gad 酸抗性调控子的调控，但 TolC 在低 pH 值和极端酸性条件下的生长中的作用尚不清楚。
在有氧条件下生长至静止期的 W3110 菌株中，TolC 对极端酸性条件（pH2）的生存是必需的。tolC 缺失使有氧生长的 pH7.0 细胞的极端酸性生存（酸抗性）降低了 10（5）倍，使 pH5.5 生长的细胞降低了 10 倍。这种需求是特定于酸抗性的，因为 tolC 缺陷对有氧条件下在极端碱性（pH10）中的生存没有影响。TolC 是谷氨酸脱羧酶（GadA、GadB）表达所必需的，谷氨酸脱羧酶是谷氨酸依赖的酸抗性（Gad）的关键组成部分。TolC 也是 E. coli K-12 W3110 在 LBK 培养基中最大指数生长的必需条件，缓冲 pH4.5-6.0，但在 pH6.5-8.5 时不需要。在中等酸度下，TolC 的生长需求与 Gad 无关。EmrB 和 MdtB 等与 TolC 相关的泵成分有助于在极端酸性（pH2）下存活，但不是在 pH5 下生长所必需的。缺乏已知的 TolC 相关外排泵（acrB、acrD、emrB、emrY、macB、mdtC、mdtF、acrEF）的突变体在酸性 pH 下没有生长缺陷，并且在预先生长在 pH5.5 时，极端酸性生存能力的下降幅度相对较小。
TolC 和质子驱动的 MDR 外排泵成分 EmrB 和 MdtB 有助于大肠杆菌在极端酸性条件下的存活，而 TolC 是 pH6.5 以下最大生长速率所必需的。TolC 增强极端酸性生存能力包括 Gad 的诱导，但 pH6.5 以下 TolC 依赖的生长速率不涉及 Gad。多药耐药性可以增强在酸性条件下的生长和存活，这对于通过酸性胃的肠道生物是一个重要的考虑因素。
