A Small RNA Transforms the Multidrug Resistance of Pseudomonas aeruginosa to Drug Susceptibility

Law, Carmen O. K.; Huang, Chuan; Pan, Qing; Lee, Joseph; Qin, Hao; Chan, Ting-Fung; Lo, Norman; Ang, Irene; Koon, Alex Chun; Ip, Margaret; Chan, Edwin; Lau, Terrence Chi-Kong

doi:10.1016/j.omtn.2019.02.011

Cited by 15 publications

(11 citation statements)

References 53 publications

(70 reference statements)

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“…sRNAs affect the stabilities and translation efficiencies of mRNAs through complementary base pairing, which is a key regulatory mechanism of bacterial gene expression (31,38,39). Although bacterial sRNAs affect a wide range of biological processes, including energy utilization and metabolism, pathogenicity, and antibiotic resistance, our understanding of the regulation of sRNAs is still limited (40)(41)(42)(43). Ribonucleases play an important role in cellular RNA metabolism processes, such as mRNA degradation and rRNA/tRNA maturation, and have emerged as the main posttranscriptional regulators of sRNAs (44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

YbeY Controls the Type III and Type VI Secretion Systems and Biofilm Formation through RetS in Pseudomonas aeruginosa

Xia

Wang

et al. 2021

Appl Environ Microbiol

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YbeY is a highly conserved RNase in bacteria and plays essential roles in the maturation of 16S rRNA, regulation of small RNAs (sRNAs) and bacterial responses to environmental stresses. Previously, we verified the role of YbeY in rRNA processing and ribosome maturation in Pseudomonas aeruginosa and demonstrated YbeY-mediated regulation of rpoS through a sRNA ReaL. In this study, we demonstrate that mutation of the ybeY gene results in upregulation of the type III secretion system (T3SS) genes as well as downregulation of the type VI secretion system (T6SS) genes and reduction of biofilm formation. By examining the expression of the known sRNAs in P. aeruginosa, we found that mutation of the ybeY gene leads to downregulation of the small RNAs RsmY/Z that control the T3SS, the T6SS and biofilm formation. Further studies revealed that the reduced levels of RsmY/Z are due to upregulation of retS. Taken together, our results reveal the pleiotropic functions of YbeY and provide detailed mechanisms of YbeY-mediated regulation in P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa causes a variety of acute and chronic infections in humans. The type III secretion system (T3SS) plays an important role in acute infection and the type VI secretion system (T6SS) and biofilm formation are associated with chronic infections. Understanding of the mechanisms that control the virulence determinants involved in acute and chronic infections will provide clues for the development of effective treatment strategies. Our results reveal a novel RNase mediated regulation on the T3SS, T6SS and biofilm formation in P. aeruginosa.

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Section: Discussionmentioning

confidence: 99%

YbeY Controls the Type III and Type VI Secretion Systems and Biofilm Formation through RetS in Pseudomonas aeruginosa

Xia

Wang

et al. 2021

Appl Environ Microbiol

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“…An increasing number of studies point toward that direction, and have been excellently reviewed by Lalaouna et al (2014), Dersch et al (2017), Felden and Cattoira (2018). The antibiotic susceptibility of multidrug-resistant (MDR) Pseudomonas aeruginosa was dramatically altered when AS1974 sRNA was overexpressed (Law et al, 2019). Authors of the study carried out a first screening on the sRNAs repertoire on three MDR clinical isolates, having found three small-regulatory RNAs that were significantly downregulated.…”

Section: Antibiotic Resistancementioning

confidence: 99%

Small RNAs as Fundamental Players in the Transference of Information During Bacterial Infectious Diseases

Plaza

2020

Front. Mol. Biosci.

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Communication shapes life on Earth. Transference of information has played a paramount role on the evolution of all living or extinct organisms since the appearance of life. Success or failure in this process will determine the prevalence or disappearance of a certain set of genes, the basis of Darwinian paradigm. Among different molecules used for transmission or reception of information, RNA plays a key role. For instance, the early precursors of life were information molecules based in primitive RNA forms. A growing field of research has focused on the contribution of small non-coding RNA forms due to its role on infectious diseases. These are short RNA species that carry out regulatory tasks in cis or trans. Small RNAs have shown their relevance in fine tuning the expression and activity of important regulators of essential genes for bacteria. Regulation of targets occurs through a plethora of mechanisms, including mRNA stabilization/destabilization, driving target mRNAs to degradation, or direct binding to regulatory proteins. Different studies have been conducted during the interplay of pathogenic bacteria with several hosts, including humans, animals, or plants. The sRNAs help the invader to quickly adapt to the change in environmental conditions when it enters in the host, or passes to a free state. The adaptation is achieved by direct targeting of the pathogen genes, or subversion of the host immune system. Pathogens trigger also an immune response in the host, which has been shown as well to be regulated by a wide range of sRNAs. This review focuses on the most recent host-pathogen interaction studies during bacterial infectious diseases, providing the perspective of the pathogen.

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“…Converting MDR bacteria to drug hyper susceptible cells is a potential approach to fight against MDR infection. It has been recently shown that the overexpression of the sRNA AS1974 in clinical isolates of MDR P. aeruginosa induces drug hyper susceptibility [ 257 ].…”

Section: Antimicrobial Strategies Related With Tcs and Associated mentioning

confidence: 99%

Interplay between Regulatory RNAs and Signal Transduction Systems during Bacterial Infection

Piattelli

Peltier

Soutourina

2020

Genes

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The ability of pathogenic bacteria to stably infect the host depends on their capacity to respond and adapt to the host environment and on the efficiency of their defensive mechanisms. Bacterial envelope provides a physical barrier protecting against environmental threats. It also constitutes an important sensory interface where numerous sensing systems are located. Signal transduction systems include Two-Component Systems (TCSs) and alternative sigma factors. These systems are able to sense and respond to the ever-changing environment inside the host, altering the bacterial transcriptome to mitigate the impact of the stress. The regulatory networks associated with signal transduction systems comprise small regulatory RNAs (sRNAs) that can be directly involved in the expression of virulence factors. The aim of this review is to describe the importance of TCS- and alternative sigma factor-associated sRNAs in human pathogens during infection. The currently available genome-wide approaches for studies of TCS-regulated sRNAs will be discussed. The differences in the signal transduction mediated by TCSs between bacteria and higher eukaryotes and the specificity of regulatory RNAs for their targets make them appealing targets for discovery of new strategies to fight against multi-resistant bacteria.

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A Small RNA Transforms the Multidrug Resistance of Pseudomonas aeruginosa to Drug Susceptibility

Cited by 15 publications

References 53 publications

YbeY Controls the Type III and Type VI Secretion Systems and Biofilm Formation through RetS in Pseudomonas aeruginosa

YbeY Controls the Type III and Type VI Secretion Systems and Biofilm Formation through RetS in Pseudomonas aeruginosa

Small RNAs as Fundamental Players in the Transference of Information During Bacterial Infectious Diseases

Interplay between Regulatory RNAs and Signal Transduction Systems during Bacterial Infection

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