CsbD, a Novel Group B Streptococcal Stress Response Factor That Contributes to Bacterial Resistance against Environmental Bile Salts.

CsbD, a Novel Group B Streptococcal Stress Response Factor That Contributes to Bacterial Resistance against Environmental Bile Salts.
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DOI:
10.1128/jb.00448-22
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发表时间:
2023-06-27
影响因子:
3.2
通讯作者:
--
中科院分区:
生物学3区
文献类型:
--
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B群链球菌(GBS)可引起许多严重感染,并根据感染器官的不同而导致严重的症状。为了存活并从胃肠道引发感染,GBS必须抵抗生理化学因素,如胆汁盐,肠道中的一种强效抗菌化合物。我们发现从不同来源分离的GBS都具有防御胆盐并允许生存的能力。通过构建GBS A909转座子突变文库(A909Tn),我们确定了几个可能参与GBS胆盐抗性的候选基因。证实rodA和csbD基因与胆盐抗性有关。预计rodA基因与肽聚糖合成有关,并通过细胞壁构建影响GBS的胆盐抗性。值得注意的是,我们发现csbD基因作为胆盐抗性应答因子并影响多个ABC转运蛋白基因,特别是在胆盐胁迫下GBS生长后期。我们进一步通过亲水相互作用色谱-液相色谱/质谱(HILIC-LC/MS)检测ΔcsbD细胞内胆盐的显著积累。总的来说,我们发现了一种新的GBS应激反应因子csbD,通过感知胆盐应激,并随后诱导转运基因转录以分泌胆盐,从而有助于胆盐中的细菌存活。GBS是人类肠道菌群的一种条件致病性定植菌,可在免疫功能低下的患者中引起严重的传染病。因此,了解对胆汁盐产生耐药性的因素是至关重要的,胆汁盐在肠道中含量丰富,但对细菌有害。我们使用转座子插入位点测序(TIS-seq)筛选鉴定了参与胆汁盐抗性的rodA和csbD基因。rodA基因产物可能参与肽聚糖的合成,是包括胆盐在内的抗逆性的重要贡献者。然而,csbD基因通过在GBS生长后期促进转运体基因的转录来促进胆盐抗性。这些发现有助于更好地了解应激反应因子csbD对GBS胆盐抗性的影响。
Group B Streptococcus (GBS) can cause many serious infections and result in severe symptoms depending on the infected organs. To survive and initiate infection from the gastrointestinal tract, GBS must resist physiochemical factors, such as bile salts, a potent antibacterial compound in the intestine. We found that GBS isolated from diverse sources all possess the capability to defend bile salts and permit survival. By constructing the GBS A909 transposon mutant library (A909Tn), we identified several candidate genes that might participate in the bile salt resistance of GBS. The rodA and csbD genes were validated as relevant to bile salt resistance. The rodA gene was anticipated to be related to peptidoglycan synthesis and influence the bile salt resistance of GBS by cell wall construction. Notably, we found that the csbD gene worked as a bile salt resistance response factor and influenced several ABC transporter genes, specifically at the later growth period of GBS under bile salt stress. We further detected the marked intracellular bile salt accumulation in ΔcsbD by hydrophilic interaction chromatography-liquid chromatography/mass spectrometry (HILIC-LC/MS). Collectively, we showed a novel GBS stress response factor, csbD, contributes to bacterial survival in bile salts by sensing bile salt stress and subsequently induces transcription of transporter genes to excrete bile salts. IMPORTANCE GBS, a conditional pathogenetic colonizer of the human intestinal flora, can cause severe infectious diseases in immunocompromised patients. Therefore, it is critical to understand the factors that contribute to the resistance to bile salts, which are abundant in the intestine but harmful to bacteria. We identified rodA and csbD genes involved in bile salt resistance using a transposon insertion site sequencing (TIS-seq) based screen. The rodA gene products might be involved in peptidoglycan synthesis as important contributors to stress resistance including bile salts. However, the csbD gene conferred bile salt resistance by promoting transporter genes transcription at the later growth period of GBS in response to bile salts. These findings developed a better understanding of the stress response factor csbD on the bile salt resistance of GBS.
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