The transcriptional regulators of virulence for Pseudomonas aeruginosa: Therapeutic opportunity and preventive potential of its clinical infections

Shao, Xiaolong; Chen, Yao; Ding, Yiqing; Hu, Haiyan; Qian, Guoliang; He, Ming; Deng, Xin

doi:10.1016/j.gendis.2022.09.009

Cited by 9 publications

(6 citation statements)

References 143 publications

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“…5A and B ) . We also tested mutants from additional regulatory pathways that control motility: Δ gacA, response-regulator of the Gac/Rsm pathway involved in virulence and motility; Δ rsmA, a posttranscriptional regulator of the Gac/Rsm pathway; Δ retS , a response regulator which can block GacA function [53]; Δ wspR, the response regulator of the Wsp chemosensory pathway [54, 55]; and Δ toxR, a c-di-GMP binding protein involved in motility and biofilm regulation [56]. The Δ retS and Δ rsmA mutants did not swarm, while the Δ gacA, Δ wspR, and Δ toxR mutants exhibited swarming similar to WT P. aeruginosa (Supp.…”

Section: Resultsmentioning

confidence: 99%

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Interspecies surfactants serve as public goods enabling surface motility inPseudomonas aeruginosa

Warrell,

Zarrella,

Machalek

et al. 2024

Preprint

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In most natural environments, bacteria live in polymicrobial communities where secreted molecules from neighboring species alter bacterial behaviors including motility, but such interactions are understudied.Pseudomonas aeruginosais a motile opportunistic pathogen that exists in diverse multispecies environments such as the soil and is frequently found in human wound and respiratory tract co-infections with other bacteria includingStaphylococcus aureus. Here we show thatP. aeruginosacan co-opt secreted molecules from other species for flagellar-based emergent motility. We found that in the presence of exoproducts fromS. aureusand other bacteria,P. aeruginosaswitched from swarming to an alternative form of motility where it slid and spread on semi-solid surfaces, and it showed similar behavior on hard agar where it was otherwise unable to move. Surfactants from these species were required for theP. aeruginosaemergent motility, and it was also induced by the addition of numerous exogenous biological and synthetic surfactants. Mutant analysis indicated that this motility was similar to a previously described mucin-basedP. aeruginosamotility, ‘surfing’, albeit with divergent regulation. Thus, our study establishes a majorP. aeruginosasurfing-like emergent motility where secreted surfactants from the host as well as neighboring bacterial and interkingdom species serve as public goods, allowingP. aeruginosato access different environmental niches.

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Section: Resultsmentioning

confidence: 99%

“…10A and B). We also tested mutants from additional regulatory pathways that control motility, including the Gac/Rsm and Wsp pathways (53)(54)(55)(56). The retS and rsmA mutants did not swarm, while the gacA, wspR, and toxR mutants exhibited swarming (Supp.…”

Section: Fig 7c)mentioning

confidence: 99%

Interspecies surfactants serve as public goods enabling surface motility inPseudomonas aeruginosa

Warrell,

Zarrella,

Machalek

et al. 2024

Preprint

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“…Many of the abovementioned virulent pathways are shared in other Pseudomonas species, but the associated TFs are largely different. Take the T3SS for example, different from the T3SS regulatory network (22 TFs and Hrp-T3SS) in P. syringae reviewed in this article, two key pathways (Gac/Rsm-T3SS and Vfr-ExsA-T3SS) regulate T3SS in P. aeruginosa [93] . GacAS is the vital switch for the upstream activation of T3SS.…”

Section: Discussionmentioning

confidence: 99%

“…In the Vfr-ExsA-T3SS pathway, Vfr is influenced by the level of cAMP, and the transcription activator ExsA directly induces the T3SS-related genes expression in P. aeruginosa . ExsA is also modulated by nine other regulators (VqsM, Fis, RcoA1, PsrA, HigB, PtrA, ExsD, MvaT/U, and HigA) [93] . However, a self-feedback regulatory pathway is shared by both species, including ExsADCE in P. aeruginosa and HrpSVG in P. syringae .…”

Section: Discussionmentioning

confidence: 99%

Virulence-related regulatory network of Pseudomonas syringae

Huang

Chen²,

Sun³

et al. 2022

Computational and Structural Biotechnology Journal

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“…It is also one of the main causes of nosocomial infections, accounting for almost 10% of such infections [ 6 ]. Cystic fibrosis patients primarily die from chronic infections and lung inflammation caused by P. aeruginosa [ 7 ]. Multidrug-resistant P. aeruginosa strains have a negative impact on patient outcomes, including increased mortality, hospital visits, length of stay, and cost [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

In Silico Identification of Lead Compounds for Pseudomonas Aeruginosa PqsA Enzyme: Computational Study to Block Biofilm Formation

et al. 2023

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Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium implicated in acute and chronic nosocomial infections and a leading cause of patient mortality. Pseudomonas aeruginosa infections are frequently associated with the development of biofilms, which give the bacteria additional drug resistance and increase their virulence. The goal of this study was to find strong compounds that block the Anthranilate-CoA ligase enzyme made by the pqsA gene. This would stop the P. aeruginosa quorum signaling system. This enzyme plays a crucial role in the pathogenicity of P. aeruginosa by producing autoinducers for cell-to-cell communication that lead to the production of biofilms. Pharmacophore-based virtual screening was carried out utilizing a library of commercially accessible enzyme inhibitors. The most promising hits obtained during virtual screening were put through molecular docking with the help of MOE. The virtual screening yielded 7/160 and 10/249 hits (ZINC and Chembridge). Finally, 2/7 ZINC hits and 2/10 ChemBridge hits were selected as potent lead compounds employing diverse scaffolds due to their high pqsA enzyme binding affinity. The results of the pharmacophore-based virtual screening were subsequently verified using a molecular dynamic simulation-based study (MDS). Using MDS and post-MDS, the stability of the complexes was evaluated. The most promising lead compounds exhibited a high binding affinity towards protein-binding pocket and interacted with the catalytic dyad. At least one of the scaffolds selected will possibly prove useful for future research. However, further scientific confirmation in the form of preclinical and clinical research is required before implementation.

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The transcriptional regulators of virulence for Pseudomonas aeruginosa: Therapeutic opportunity and preventive potential of its clinical infections

Cited by 9 publications

References 143 publications

Interspecies surfactants serve as public goods enabling surface motility inPseudomonas aeruginosa

Interspecies surfactants serve as public goods enabling surface motility inPseudomonas aeruginosa

Virulence-related regulatory network of Pseudomonas syringae

In Silico Identification of Lead Compounds for Pseudomonas Aeruginosa PqsA Enzyme: Computational Study to Block Biofilm Formation

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