The Small RNA AmiL Regulates Quorum Sensing-Mediated Virulence in Pseudomonas aeruginosa PAO1

Pu, Jieying; Zhang, Shebin; He, Xi; Zeng, Jianming; Cong, Shan; Luo, Yanfen; Li, Honglin; Long, Yifei; Liu, Jianping; Xiao, Qian; Lü, Yang; Huang, Bin; Cha, Chen

doi:10.1128/spectrum.02211-21

Cited by 18 publications

(18 citation statements)

References 65 publications

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“…50 Previous studies have shown that the QS system of PA is often directly regulated by transcriptional regulators. [51][52][53] According to our result, we speculate that PtrA may directly act on the QS system of PA. However, which system PtrA mainly acts on and how it affects the interaction of each system needs to be further explored in our subsequent research.…”

Section: Discussionsupporting

confidence: 59%

Novel Insight of Transcription Factor PtrA on Pathogenicity and Carbapenems Resistance in Pseudomonas aeruginosa

Zhang¹,

Wang²,

Chen³

et al. 2022

IDR

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Introduction Globally, Pseudomonas aeruginosa (PA) is emerging as a predominant nosocomial pathogen that often induces aggressive and even deadly infections. Pseudomonas type III repressor A (PtrA) can be activated specifically by copper ions and interacts with type-III transcriptional activator ExsA. This study aims to provide insight into the PtrA-mediated regulation of the pathogenicity and antibiotics resistance of PA. Methods and Results The results of transcriptome sequencing analyses and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) showed that PtrA plays a dual regulatory role in the virulence systems of PA: negatively regulates the type-III secretion system (T3SS) and positively regulates the quorum-sensing system (QS). The ptrA mutant attenuated extracellular virulence related to QS like pyocyanin, elastase, rhamnolipids, proteolytic activity, and biofilm production. According to adhesion and invasion experiments, PtrA can not only contribute to the adhesiveness but also the invasive of PA. Moreover, the PtrA-mediated regulation of PA pathogenicity was determined both in vivo and in vitro through cytotoxicity and Galleria mellonella survival experiments. In addition, apart from virulence, PtrA was found to influence the carbapenems resistance of PA. After deleting ptrA , the minimum inhibitory concentration (MIC) of carbapenems antibiotics was decreased by 2-fold, while a 2–8 fold increase was noted for the complemented strain. Conclusion Our findings establish that PtrA exerts a regulatory role in both pathogenicity and carbapenems resistance of PA. This work may shed light on a novel target for the clinical treatment of PA.

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Section: Discussionsupporting

confidence: 59%

Novel Insight of Transcription Factor PtrA on Pathogenicity and Carbapenems Resistance in Pseudomonas aeruginosa

Zhang¹,

Wang²,

Chen³

et al. 2022

IDR

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“…Our results indicate that the TYR64 residue is crucial in stabilizing complex formation. The binding of C4-HSL to RhlR activates the transcription of many virulent genes of P. aeruginosa (Pu et al 2022;Mohajeri et al 2022;Ochsner et al 1994;Pearson et al 1995). These docking results suggest that the use of metal/metal oxide nanoparticles to inhibit quorum sensing in P. aeruginosa may present a good strategy since these inhibitors seem to speci cally compete against native ligand (C4-HSL) to interact with RhlR and ultimately reduce the expression of QScontrolled genes.…”

Section: Resultsmentioning

confidence: 92%

In silico study of anti-quorum sensing activity of silver, zinc oxide, and copper oxide nanoparticles against Pseudomonas aeruginosa

Sadoq

Britel

Bouajaj

et al. 2023

Preprint

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In recent years, Pseudomonas aeruginosa emerged as a significant pathogenic microorganism in the majority of hospital-acquired infections due to the elevated levels of resistance to antibacterial agents by virtue of its highly organized quorum sensing (QS). P. aeruginosa has three hierarchical major QS systems (LasI/R, RhlI/R, and PqsA/R) that are involved in the secretion of virulence factors, biofilm formation, and antimicrobial resistance. Thus, targeting the QS mechanism may be a good strategy to combat infection caused by P. aeruginosa. In the present study, in silico analysis by molecular docking simulation of anti-quorum sensing activities of silver, zinc oxide and copper oxide against P. aeruginosa strain have been evaluated. Molecular docking showed that metal/metal oxide interaction with Acyl-Homoserine-Lactone synthases (LasI, RhlI, PqsA) can prevent precursor molecule binding and therefore inhibit the synthesis of functional signaling molecules. In addition, the binding of these nanoparticles to regulatory proteins (LasR, RhlR, PqsR) decreases the expression of QS-controlled genes by competing with functional signaling molecules for interaction with regulatory proteins. Thus, our results revealed that ZnO possesses good binding properties towards the selected targets. Particularly, the PqsA-ZnO complex shows more stable active binding sites and better binding affinity (-3.83 kcal/mol) with an inhibitory constant (Ki) of 1.65 mM. The binding mode of ZnO nanoparticles (NPs) has been found to be more potent compared to Ag and CuO NPs and related to the virulence factors of Gram-negative bacterial pathogens. This suggests that ZnO NPs could potentially be developed as effective inhibitors of QS systems and biofilms.

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“…Results of this investigation showed that deficiency of lasI or rhlI favored the survival of PAO1 when exposed to 2 or 4 mg/l of AMK ( Figures 5B , C ). Moreover, previous transcriptome sequencing data ( Pu et al, 2022 ) had found that deficiency of lasI or rhlI observably depressed expression of several genes, especially the virulence-related genes and impaired virulence such as pyocyanin, rhamnolipid synthesis and biofilm formation ( Supplementary Table 3 ; Supplementary Figure 5 ). Therefore, it was inferred that lasI and rhlI deficiency-mediated downregulation of the genes resulted in lower consumption, which could be one of the strategies for bacteria to adapt to the Sub-MIC of antibiotic pressure before resistance is acquired.…”

Section: Resultsmentioning

confidence: 95%

Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa

et al. 2022

Self Cite

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The prevalence and genetic mechanism of antibiotic heteroresistance (HR) have attracted significant research attention recently. However, non-genetic mechanism of HR has not been adequately explored. The present study aimed to evaluate the role of quorum sensing (QS), an important mechanism of behavioral coordination in different subpopulations and consequent heteroresistance. First, the prevalence of HR to 7 antibiotics was investigated in 170 clinical isolates of P. aeruginosa using population analysis profiles. The results showed that P. aeruginosa was significantly heteroresistant to meropenem (MEM), amikacin (AMK), ciprofloxacin (CIP), and ceftazidime (CAZ). The observed HR was correlated with down-regulation of QS associated genes lasI and rhlI. Further, loss-of-function analysis results showed that reduced expression of lasI and rhlI enhanced HR of P. aeruginosa to MEM, AMK, CIP, and CAZ. Conversely, overexpression of these genes or treatment with 3-oxo-C12-HSL/C4-HSL lowered HR of P. aeruginosa to the four antibiotics. Additionally, although downregulation of oprD and upregulation of efflux-associated genes was evident in heteroresistant subpopulations, their expression was not regulated by LasI and RhlI. Moreover, fitness cost measurements disclosed higher growth rates of PAO1ΔlasI and PAO1ΔrhlI in the presence of sub-MIC antibiotic as compared with that of wild-type PAO1. Our data suggest that under temporary antibiotic pressure, downregulation of QS might result in less fitness cost and promote HR of P. aeruginosa.

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The Small RNA AmiL Regulates Quorum Sensing-Mediated Virulence in Pseudomonas aeruginosa PAO1

Abstract: P. aeruginosa is a common nosocomial pathogen that causes diverse opportunistic infections in humans. The virulence crucial for infection is mainly regulated by QS.

Cited by 18 publications

References 65 publications

Novel Insight of Transcription Factor PtrA on Pathogenicity and Carbapenems Resistance in Pseudomonas aeruginosa

Novel Insight of Transcription Factor PtrA on Pathogenicity and Carbapenems Resistance in Pseudomonas aeruginosa

In silico study of anti-quorum sensing activity of silver, zinc oxide, and copper oxide nanoparticles against Pseudomonas aeruginosa

Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa

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