Histone-like nucleoid-structuring protein (H-NS) regulatory role in antibiotic resistance in Acinetobacter baumannii.
Histone-like nucleoid-structuring protein (H-NS) regulatory role in antibiotic resistance in Acinetobacter baumannii.
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DOI：
10.1038/s41598-021-98101-w
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发表时间：
2021-09-16
影响因子：
4.6
通讯作者：
Ramirez MS
中科院分区：
文献类型：
--
作者：
Rodgers D;Le C;Pimentel C;Tuttobene MR;Subils T;Escalante J;Nishimura B;Vescovi EG;Sieira R;Bonomo RA;Tolmasky ME;Ramirez MS
在多重耐药 (MDR) 病原体鲍曼不动杆菌中，全局阻遏物 H-NS 被证明可以调节参与发病机制和应激反应的基因的表达。此外，H-NS 失活会导致对粘菌素的抵抗力增加，并导致过度运动表型和应激反应的改变。为了进一步加深对鲍曼不动杆菌行为中这一关键转录调节因子的了解，我们研究了 H-NS 在抗菌素耐药性中的作用。使用两种具有独特耐药性和致病性特征的鲍曼不动杆菌模型菌株（AB5075 和 A118），采用互补的转录组学和表型方法来研究 H-NS 在抗菌素耐药性、生物膜和群体感应基因表达中的作用。在 Δhns 突变体背景中观察到与 β-内酰胺耐药性、氨基糖苷类、喹诺酮类、氯霉素、甲氧苄啶和磺胺类耐药相关的基因表达增加。除adeFGH 外，编码外排泵的基因也上调。互补菌株中恢复了野生型转录水平。此外，当转录阻遏蛋白缺失时，生物膜相关基因的表达和生物膜的产生都会降低。群体网络基因 aidA、abaI、kar 和 fadD 在 Δhns 突变株中上调。总体而言，我们的结果显示了 H-NS（涉及抗生素耐药性和持久性的基因）控制的调控网络的复杂性和范围。这些观察结果使我们更进一步了解 hns 在对抗鲍曼不动杆菌感染中的调节作用。
In the multidrug resistant (MDR) pathogen Acinetobacter baumannii the global repressor H-NS was shown to modulate the expression of genes involved in pathogenesis and stress response. In addition, H-NS inactivation results in an increased resistance to colistin, and in a hypermotile phenotype an altered stress response. To further contribute to the knowledge of this key transcriptional regulator in A. baumannii behavior, we studied the role of H-NS in antimicrobial resistance. Using two well characterized A. baumannii model strains with distinctive resistance profile and pathogenicity traits (AB5075 and A118), complementary transcriptomic and phenotypic approaches were used to study the role of H-NS in antimicrobial resistance, biofilm and quorum sensing gene expression. An increased expression of genes associated with β-lactam resistance, aminoglycosides, quinolones, chloramphenicol, trimethoprim and sulfonamides resistance in the Δhns mutant background was observed. Genes codifying for efflux pumps were also up-regulated, with the exception of adeFGH. The wild-type transcriptional level was restored in the complemented strain. In addition, the expression of biofilm related genes and biofilm production was lowered when the transcriptional repressor was absent. The quorum network genes aidA, abaI, kar and fadD were up-regulated in Δhns mutant strains. Overall, our results showed the complexity and scope of the regulatory network control by H-NS (genes involved in antibiotic resistance and persistence). These observations brings us one step closer to understanding the regulatory role of hns to combat A. baumannii infections.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
4.9
作者：
Lucas, Deanna Deveson;Crane, Bethany;Boyce, John D.
通讯作者：
Boyce, John D.
影响因子：
4.2
作者：
Lin MF;Lin YY;Yeh HW;Lan CY
通讯作者：
Lan CY
影响因子：
3.2
作者：
López-Martín M;Dubern JF;Alexander MR;Williams P
通讯作者：
Williams P
影响因子：
3.2
作者：
Domingues, Sara;Rosario, Natasha;Da Silva, Gabriela Jorge
通讯作者：
Da Silva, Gabriela Jorge