A Pseudomonas aeruginosa small RNA regulates chronic and acute infection

Cao, Pengbo; Fleming, Derek; Moustafa, Dina A.; Dolan, Stephen K.; Szymanik, Kayla H.; Redman, Whitni K.; Ramos, Anayancy; Diggle, Frances L.; Sullivan, Christopher S.; Goldberg, Joanna B.; Rumbaugh, Kendra P.; Whiteley, Marvin

doi:10.1038/s41586-023-06111-7

Cited by 45 publications

(9 citation statements)

References 63 publications

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“…Moreover, the recently characterized small RNA, sicX , encoded by PA14_46160 was upregulated ∼6 times. It is worth noting that sicX was found to be induced by low oxygen and is important in the transition between chronic and acute infection stages in P. aeruginosa [45].…”

Section: Resultsmentioning

confidence: 99%

Global stress response inPseudomonas aeruginosaupon malonate utilization

Bisht,

Elmassry,

Al Mahmud

et al. 2024

Preprint

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Versatility in carbon source utilization assistsPseudomonas aeruginosain its adaptation to various niches. Recently, we characterized the role of malonate, an understudied carbon source, in quorum sensing regulation, antibiotic resistance, and virulence factor production inP. aeruginosa. These results indicate that global responses to malonate metabolism remain to be uncovered. We leveraged a publicly available metabolomic dataset on human airway and found malonate to be as abundant as glycerol, a common airway metabolite and carbon source forP. aeruginosa. Here, we explored and compared adaptations ofP. aeruginosaUCBPP-PA14 (PA14) in response to malonate or glycerol as a sole carbon source using transcriptomics and phenotypic assays. Malonate utilization activated glyoxylate and methylcitrate cycles and induced several stress responses, including oxidative, anaerobic, and metal stress responses associated with increases in intracellular aluminum and strontium. Some induced genes were required for optimal growth ofP. aeruginosain malonate. To assess the conservation of malonate-associated responses amongP. aeruginosastrains, we compared our findings in strain PA14 with other lab strains and cystic fibrosis isolates ofP. aeruginosa. Most strains grew on malonate as a sole carbon source as efficiently as or better than glycerol. While not all responses to malonate were conserved among strains, formation of biomineralized biofilm-like aggregates, increased tolerance to kanamycin, and increased susceptibility to norfloxacin were the most frequently observed phenotypes. Our findings reveal global remodeling ofP. aeruginosagene expression during its growth on malonate as a sole carbon source that is accompanied by several important phenotypic changes. These findings add to accumulating literature highlighting the role of different carbon sources in the physiology ofP. aeruginosaand its niche adaptation.ImportancePseudomonas aeruginosais a notorious pathogen that causes local and systemic infections in immunocompromised individuals. Different carbon sources can uniquely modulate metabolic and virulence pathways inP. aeruginosa, highlighting the importance of the environment that the pathogen occupies. In this work, we used a combination of transcriptomic analysis and phenotypic assays to determine how malonate utilization impactsP. aeruginosa,as recent evidence indicates this carbon source may be relevant to certain niches associated within the human host. We found that malonate utilization can induce global stress responses, alter metabolic circuits, and influence various phenotypes ofP. aeruginosathat could influence host colonization. Investigating the metabolism of malonate provides insight intoP. aeruginosaadaptations to specific niches where this substrate is abundant, and how it can be leveraged in the development of much-needed antimicrobial agents or identification of new therapeutic targets of this difficult-to-eradicate pathogen.

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Section: Resultsmentioning

confidence: 99%

Global stress response inPseudomonas aeruginosaupon malonate utilization

Bisht,

Elmassry,

Al Mahmud

et al. 2024

Preprint

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“…The presence of only one set of diffraction patterns suggested that it can be regarded as a single-phase solid solution alloy. 24 XRD patterns of support HEA NPs in Fig. 1(b) reveal that the Fe 1 Co 1.5 Ni 1 Cu 1.5 Pt 1.5 /C HEA has a face-centered cubic (fcc) structure, similar to that of pure Pt NPs.…”

Section: Resultsmentioning

confidence: 99%

Accelerating oxidation of 5-hydroxymethylfurfural into 2,5-furandicarboxylic acid by high entropy alloy catalyst design under base-free conditions

Liu¹,

Chen²,

Gao³

et al. 2023

Sustainable Energy Fuels

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“…For example, P. aeruginosa sRNA PrrF was found to be required for PQS production and bacterial virulence in response to low iron conditions in a murine model of acute lung infection 27 . Another P. aeruginosa sRNA SicX was recently found to be highly expressed in human chronic wound and cystic fibrosis infections, SicX was induced under low oxygen levels to regulate anaerobic ubiquinone biosynthesis for promoting the chronic infection through biofilm formation and inhibiting acute mice infections 28 .…”

Section: Introductionmentioning

confidence: 99%

The Hfq-binding small RNA PqsS regulates Pseudomonas aeruginosa pqs quorum sensing system and virulence

Yang,

JIA,

et al. 2024

Preprint

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Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant capacity to cause both severe acute infections and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq, triggering various signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, named PqsS, which promoted bacterial pathogenicity and the pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced bacterial acute infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation, antibiotic resistance, macrophage survival, and ROS production. Moreover, PqsS repressed the pqsL transcript, leading to the increased PQS levels for pqs QS system, while a PQS-rich condition promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS-Hfq complex interacts with and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. Finally, PqsS promotes membrane vesicles (MVs) production and is abundantly detected in MVs. Our work revealed a novel Hfq-binding sRNA PqsS signaling pathway, which enhances pqs QS and acute infections in P. aeruginosa. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment strategies.

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A Pseudomonas aeruginosa small RNA regulates chronic and acute infection

Cited by 45 publications

References 63 publications

Global stress response inPseudomonas aeruginosaupon malonate utilization

Global stress response inPseudomonas aeruginosaupon malonate utilization

Accelerating oxidation of 5-hydroxymethylfurfural into 2,5-furandicarboxylic acid by high entropy alloy catalyst design under base-free conditions

The Hfq-binding small RNA PqsS regulates Pseudomonas aeruginosa pqs quorum sensing system and virulence

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