Chemical inhibitors of the conserved bacterial transcriptional regulator DksA1 suppressed quorum sensing-mediated virulence of Pseudomonas aeruginosa

Abstract

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The two Pseudomonas aeruginosa DksA stringent response proteins are largely interchangeable at the whole transcriptome level and in the control of virulence‐related traits

“…aeruginosa virulence by oxidizing the Zn‐coordinating cysteine thiols of DksA1 globular domain, hence affecting protein binding to RNAP. However, the effect of DKST‐1 and DKST‐2 on DksA2 activity was not investigated (Min et al ., 2021). Overall, also considering the different structure of DksA1 and DksA2 globular domains, our study indicates that DksA2 should not be overlooked in this context.…”

“…These systems have extensively been studied in the last decades due to their promise as targets for innovative anti-Pseudomonas drugs (Rampioni et al, 2014;Valentini and Filloux, 2016). Since the stringent response also plays a major role in P. aeruginosa pathogenesis, it recently gained new attention as a target for anti-virulence strategies (Min and Yoon, 2020;Pletzer et al, 2020;Min et al, 2021). Interestingly, two dksA paralogs were identified in the P. aeruginosa genome, namely dksA1 (dksA in earlier studies) and dksA2.…”

“…Since the stringent response also plays a major role in P . aeruginosa pathogenesis, it recently gained new attention as a target for anti‐virulence strategies (Min and Yoon, 2020; Pletzer et al ., 2020; Min et al ., 2021).…”

Functional Amyloids in Pseudomonas aeruginosa Are Essential for the Proteome Modulation That Leads to Pathoadaptation in Pulmonary Niches

“…The absence of Fap suppressed the interactomes associated with biofilm formation, stress response, and cellular integrity in PAO1 Δfap and effaced matrix-mediated defense, leading to decreased pathogenesis. The DksA involvement in infection establishment and motility regulation explained why its downregulation in PAO1 Δfap affected initial attachment to lung surfaces ( 65 ). Higher DspI and SuhB expression levels shifted PAO1 Δfap to planktonic lifestyle, making it susceptible to host immune response, bacterial clearance, and mild bacteremia in the HWB model.…”