Rotstein O D, Nasmith P E, Grinstein S
Infect Immun. 1987 Apr;55(4):864-70. doi: 10.1128/iai.55.4.864-870.1987.
Short-chain fatty acids, particularly succinic acid, are major metabolic by-products of Bacteroides species. To determine their role as potential virulence factors in infections containing Bacteroides species, short-chain fatty acids were examined for their effect on the neutrophil respiratory burst. Succinate (30 to 50 mM) irreversibly impaired superoxide and hydrogen peroxide production in response to opsonized zymosan and phorbol myristate acetate when neutrophils were treated at pH 5.5 but not pH 6.0 or greater. Several other short-chain fatty acids tested produced similar inhibition. Reversible inhibition of oxygen consumption was found when neutrophils were incubated in succinate-containing medium (pH 6.0) as well as control medium (pH 6.0 and 5.5). Neutrophil cytoplasmic pH was measured by fluorimetric techniques to determine whether the inhibition was mediated via a reduction in intracellular pH. The intracellular pH of cells in control medium (pH 6.5 or less) was significantly reduced compared with pH 7.4. The addition of succinate (30 mM) to these media caused a further significant reduction in cytoplasmic pH at each pH level. The reduction in intracellular pH was sufficient to account for both the irreversible and reversible impairment of the neutrophil respiratory burst. Thus, short-chain fatty acids appear to exert their inhibition, at least in part, by reducing intracellular pH. These data also demonstrate the potential for interactions between Bacteroides species and their microenvironment to increase the virulence of an infection.
短链脂肪酸，尤其是琥珀酸，是拟杆菌属的主要代谢副产物。为了确定它们作为拟杆菌属感染中潜在毒力因子的作用，研究了短链脂肪酸对中性粒细胞呼吸爆发的影响。当在pH 5.5而非pH 6.0或更高的条件下处理中性粒细胞时，琥珀酸盐（30至50 mM）会不可逆地损害其对调理酵母聚糖和佛波醇肉豆蔻酸酯乙酸盐的超氧化物和过氧化氢生成。测试的其他几种短链脂肪酸也产生了类似的抑制作用。当将中性粒细胞在含琥珀酸盐的培养基（pH 6.0）以及对照培养基（pH 6.0和5.5）中孵育时，发现对氧消耗有可逆性抑制。通过荧光技术测量中性粒细胞胞质pH，以确定这种抑制是否通过细胞内pH降低介导。与pH 7.4相比，对照培养基（pH 6.5或更低）中细胞的细胞内pH显著降低。向这些培养基中添加琥珀酸盐（30 mM）会导致每个pH水平下胞质pH进一步显著降低。细胞内pH的降低足以解释中性粒细胞呼吸爆发的不可逆和可逆损害。因此，短链脂肪酸似乎至少部分地通过降低细胞内pH来发挥其抑制作用。这些数据还证明了拟杆菌属与其微环境之间相互作用增加感染毒力的可能性。
