Bacterial small proteins (below 50 amino acids) encoded by small open reading frames (sORFs) are recognized as an emerging class of functional molecules that have been largely overlooked in the past. While some were uncovered serendipitously, global approaches have recently been developed to detect these sORFs. A large portion of small proteins appears to be hydrophobic and located in the bacterial membrane. In the present review, we describe functional small hydrophobic proteins discovered in pathogenic bacteria and report recent advances in the discovery of additional ones. Small membrane proteins contribute to bacterial adaptation to changing environments and often appear to be implicated in negative feedback regulation loops by modulating the function or stability of larger membrane proteins. A subset of these proteins belongs to toxin‐antitoxin modules. We highlight the features of characterized hydrophobic small proteins that may pave the way for identification of the functional small proteins among novel sORFs discovered. Besides providing new insights into bacterial pathogenesis, identification of naturally occurring small hydrophobic proteins of pathogenic bacteria can lead to new therapeutic interventions, as recently shown with the development of synthetic peptides derived from natural small proteins that display antibacterial or antivirulence properties.

中文翻译：

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发现病原菌中的小膜蛋白：调节功能和治疗潜力。

由小型开放阅读框 (sORF) 编码的细菌小蛋白（低于 50 个氨基酸）被认为是一类新兴的功能分子，而这些功能分子过去在很大程度上被忽视了。虽然有些是偶然发现的，但最近已经开发出全球方法来检测这些 sORF。大部分小蛋白质似乎是疏水的，位于细菌膜中。在本综述中，我们描述了在致病细菌中发现的功能性小疏水蛋白，并报告了发现其他蛋白质的最新进展。小膜蛋白有助于细菌适应不断变化的环境，并且通常似乎通过调节较大膜蛋白的功能或稳定性而参与负反馈调节回路。这些蛋白质的一个子集属于毒素-抗毒素模块。我们强调了表征疏水性小蛋白的特征，这些特征可能为在发现的新型 sORF 中鉴定功能性小蛋白铺平道路。除了提供对细菌发病机制的新见解外，鉴定病原细菌的天然存在的小疏水蛋白可以导致新的治疗干预，正如最近开发的源自天然小蛋白的合成肽所示，这些蛋白显示出抗菌或抗毒力特性。