Table_4_Transcriptome reveals the role of the htpG gene in mediating antibiotic resistance through cell envelope modulation in Vibrio mimicus SCCF01.xls

HtpG, a bacterial homolog of the eukaryotic 90 kDa heat-shock protein (Hsp90), represents the simplest member of the heat shock protein family. While the significance of Hsp90 in fungal and cancer drug resistance has been confirmed, the role of HtpG in bacterial antibiotic resistance remains largely unexplored. This research aims to investigate the impact of the htpG gene on antibiotic resistance in Vibrio mimicus. Through the creation of htpG gene deletion and complementation strains, we have uncovered the essential role of htpG in regulating the structural integrity of the bacterial cell envelope. Our transcriptomics analysis demonstrates that the deletion of htpG increases the sensitivity of V. mimicus to antimicrobial peptides, primarily due to upregulated lipopolysaccharide synthesis, reduced glycerophospholipid content, and weakened efflux pumps activity. Conversely, reduced sensitivity to β-lactam antibiotics in the ΔhtpG strain results from decreased peptidoglycan synthesis and dysregulated peptidoglycan recycling and regulation. Further exploration of specific pathway components is essential for a comprehensive understanding of htpG-mediated resistance mechanisms, aiding in the development of antimicrobial agents. To our knowledge, this is the first effort to explore the relationship between htpG and drug resistance in bacteria.

HtpG作为真核90 kDa热休克蛋白（Hsp90）的细菌同源物，属于热休克蛋白家族中结构最为简单的成员。尽管Hsp90在真菌与癌症耐药性中的关键作用已得到证实，但HtpG在细菌抗生素耐药性中所扮演的角色仍有待深入探究。本研究旨在剖析htpG基因对拟态弧菌（Vibrio mimicus）抗生素耐药性的影响。通过构建htpG基因敲除与互补菌株，本研究揭示了htpG在调控细菌细胞包膜结构完整性方面的核心功能。转录组学分析结果显示，htpG基因敲除会提升拟态弧菌对各类抗菌肽的敏感性，其主要原因为脂多糖合成上调、甘油磷脂含量降低以及外排泵活性减弱。与之相反，htpG缺失株（ΔhtpG）对β-内酰胺类抗生素的敏感性降低，则源于肽聚糖合成减少、肽聚糖循环与调控通路失调。若要全面解析htpG介导的耐药机制，进而为抗菌药物的研发提供支撑，对相关通路特定组分的深入探究不可或缺。据我们所知，本研究是首次探索htpG与细菌耐药性之间关联的相关工作。