Both fermentative and respiratory processes contribute to bacterial metabolic adaptations to low oxygen tension (hypoxia). In the absence of O₂ as a respiratory electron sink, many bacteria utilize alternative electron acceptors, such as nitrate (NO₃⁻). During canonical NO₃⁻ respiration, NO₃⁻ is reduced in a stepwise manner to N₂ by a dedicated set of reductases. Vibrio cholerae, the etiological agent of cholera, requires only a single periplasmic NO₃⁻ reductase (NapA) to undergo NO₃⁻ respiration, suggesting that the pathogen possesses a noncanonical NO₃⁻ respiratory chain. In this study, we used complementary transposon-based screens to identify genetic determinants of general hypoxic growth and NO₃⁻ respiration in V. cholerae. We found that while the V. cholerae NO₃⁻ respiratory chain is primarily composed of homologues of established NO₃⁻ respiratory genes, it also includes components previously unlinked to this process, such as the Na⁺-NADH dehydrogenase Nqr. The ethanol-generating enzyme AdhE was shown to be the principal fermentative branch required during hypoxic growth in V. cholerae. Relative to single adhE or napA mutant strains, a V. cholerae strain lacking both genes exhibited severely impaired hypoxic growth in vitro and in vivo. Our findings reveal the genetic basis of a specific interaction between disparate energy production pathways that supports pathogen fitness under shifting conditions. Such metabolic specializations in V. cholerae and other pathogens are potential targets for antimicrobial interventions.

中文翻译：

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支持霍乱弧菌缺氧生长的发酵和呼吸贡献的遗传解剖。

发酵和呼吸过程都有助于细菌代谢适应低氧张力（缺氧）。在没有 O ₂作为呼吸电子汇的情况下，许多细菌利用替代电子受体，例如硝酸盐 (NO ₃ ^- )。在典型的 NO ₃ ^-呼吸过程中，NO ₃ ^-被一组专用的还原酶逐步还原为 N _{2 。}霍乱弧菌是霍乱的病原体，仅需要单一周质NO ₃ ^-还原酶（NapA）即可进行NO ₃ ^-呼吸，这表明该病原体拥有非典型的NO ₃ ^-呼吸链。在这项研究中，我们使用基于转座子的互补筛选来鉴定霍乱弧菌一般缺氧生长和 NO ₃ ^-呼吸的遗传决定因素。我们发现，虽然霍乱弧菌NO ₃ ^{-呼吸链主要由已建立的 NO} ₃ ^-呼吸基因的同源物组成，但它也包括以前与该过程无关的成分，例如 Na ⁺ -NADH 脱氢酶 Nqr。乙醇生成酶 AdhE 被证明是霍乱弧菌缺氧生长期间所需的主要发酵分支。相对于单一的adhE或napA突变菌株，缺乏这两种基因的霍乱弧菌菌株在体外和体内表现出严重受损的缺氧生长。我们的研究结果揭示了不同能量生产途径之间特定相互作用的遗传基础，这种相互作用支持病原体在变化条件下的适应性。霍乱弧菌和其他病原体的这种代谢特化是抗菌干预的潜在目标。