Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Infect Immun. 2018 Jan 22;86(2). doi: 10.1128/IAI.00547-17. Print 2018 Feb.
Enterotoxin-producing type A strains cause human gastrointestinal (GI) infections, including a very common food poisoning and 5 to 10% of all cases of antibiotic-associated diarrhea. This bacterium can utilize free sialic acid for growth, but most sialic acids in the GI tract are sequestered on macromolecules, such as the mucin proteins of mucus or glycoconjugates in host cells. However, many strains produce sialidases that might promote growth and survival by generating free sialic acid from those sialyated host macromolecules or by exposing underlying carbohydrates or proteins for digestion by other enzymes. The current study tested that possibility and found that the nonfoodborne human GI disease strain F4969 can use either a mucin preparation or Caco-2 cells, which are human enterocyte-like cells, to support its growth and survival. An isogenic null mutant and complemented strain were used to show that this enhanced growth and survival using mucin or Caco-2 cells involved NanI, which is the major exosialidase of F4969 and many other strains. Experiments also suggested that, at least in part, this growth promotion involves utilization of NanI-generated sialic acid. In addition, a sialidase inhibitor named siastatin B reduced the growth and survival of F4969 growing with either the mucin preparation or Caco-2 cells. These findings suggest that, when produced, NanI may be a significant contributor to human GI infections by promoting the intestinal growth and survival of this bacterium. They also suggest the possibility that sialidase inhibitors might inhibit infections.
产肠毒素 A 型菌株引起人类胃肠道 (GI) 感染，包括非常常见的食物中毒和 5%至 10%的所有抗生素相关性腹泻病例。这种细菌可以利用游离唾液酸进行生长，但 GI 道中的大多数唾液酸都被固定在大分子上，如粘液中的粘蛋白或宿主细胞中的糖缀合物。然而，许多菌株产生唾液酸酶，这些酶可以通过从那些唾液酸化的宿主大分子中产生游离唾液酸，或者通过暴露潜在的碳水化合物或蛋白质供其他酶消化，从而促进生长和存活。本研究检验了这种可能性，发现非食源性人类 GI 疾病菌株 F4969 可以使用粘蛋白制剂或 Caco-2 细胞（人肠上皮样细胞）来支持其生长和存活。使用同源缺失突变体和互补菌株表明，这种使用粘蛋白或 Caco-2 细胞增强的生长和存活涉及 NanI，它是 F4969 和许多其他 菌株的主要外唾液酸酶。实验还表明，至少部分原因是这种生长促进作用涉及利用 NanI 产生的唾液酸。此外，一种名为 siastatin B 的唾液酸酶抑制剂减少了 F4969 在粘蛋白制剂或 Caco-2 细胞上生长的生长和存活。这些发现表明，当产生时，NanI 可能通过促进这种细菌在肠道中的生长和存活，成为人类 GI 感染的重要贡献者。它们还表明，唾液酸酶抑制剂可能抑制 感染的可能性。
