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是真核生物90 kDa热休克蛋白（heat shock protein 90, Hsp90）的细菌同源蛋白，亦是热休克蛋白家族中结构最为简约的成员。尽管Hsp90在真菌与癌症耐药性中的功能已得到验证，但HtpG在细菌抗生素耐药性中的作用仍未得到充分探索。本研究旨在探究htpG基因对拟态弧菌（Vibrio mimicus）抗生素耐药性的影响。通过构建htpG基因缺失株与互补株，我们揭示了htpG在调控细菌细胞包膜结构完整性中的核心作用。本研究的转录组学（transcriptomics）分析结果显示，htpG基因缺失会提升拟态弧菌对抗菌肽（antimicrobial peptides）的敏感性，该现象主要源于脂多糖（lipopolysaccharide）合成上调、甘油磷脂（glycerophospholipid）含量降低以及外排泵（efflux pumps）活性减弱。与之相反，ΔhtpG菌株对β-内酰胺类抗生素（β-lactam antibiotics）的敏感性降低，其机制为肽聚糖（peptidoglycan）合成减少以及肽聚糖循环与调控通路失衡。若要全面解析htpG介导的细菌耐药机制并助力抗菌药物的研发，对其特定通路组分开展深入探究至关重要。据我们所知，本研究是首个探索细菌中htpG与耐药性关联的研究工作。