Networks of Resistance: Small RNA Control of Antibiotic Resistance

Mediati, Daniel G.; Wu, Sylvania; Wu, Winton; Tree, Jai J.

doi:10.1016/j.tig.2020.08.016

Cited by 41 publications

(33 citation statements)

References 79 publications

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“…Likewise, rRNAs and tRNAs could boost translation in EV recipient bacterial cells and improve their fitness. In bacteria, sRNAs fine tune target gene expression, usually at the posttranscriptional level in response to changes in the environment, including antibiotic resistance and tolerance (Mediati et al, 2021). Most bacteria encode dozens of sRNAs that are transcribed as independent transcripts or processed from mRNAs.…”

Section: Discussionmentioning

confidence: 99%

Environmental Plasticity of the RNA Content of Staphylococcus aureus Extracellular Vesicles

et al. 2021

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The roles of bacterial extracellular vesicles (EVs) in cell-to-cell signaling are progressively being unraveled. These membranous spheres released by many living cells carry various macromolecules, some of which influence host-pathogen interactions. Bacterial EVs contain RNA, which may serve in communicating with their infected hosts. Staphylococcus aureus, an opportunistic human and animal pathogen, produces EVs whose RNA content is still poorly characterized. Here, we investigated in depth the RNA content of S. aureus EVs. A high-throughput RNA sequencing approach identified RNAs in EVs produced by the clinical S. aureus strain HG003 under different environmental conditions: early- and late-stationary growth phases, and presence or absence of a sublethal vancomycin concentration. On average, sequences corresponding to 78.0% of the annotated transcripts in HG003 genome were identified in HG003 EVs. However, only ~5% of them were highly covered by reads (≥90% coverage) indicating that a large fraction of EV RNAs, notably mRNAs and sRNAs, were fragmented in EVs. According to growth conditions, from 86 to 273 highly covered RNAs were identified into the EVs. They corresponded to 286 unique RNAs, including 220 mRNAs. They coded for numerous virulence-associated factors (hld encoded by the multifunctional sRNA RNAIII, agrBCD, psmβ1, sbi, spa, and isaB), ribosomal proteins, transcriptional regulators, and metabolic enzymes. Twenty-eight sRNAs were also detected, including bona fide RsaC. The presence of 22 RNAs within HG003 EVs was confirmed by reverse transcription quantitative PCR (RT-qPCR) experiments. Several of these 286 RNAs were shown to belong to the same transcriptional units in S. aureus. Both nature and abundance of the EV RNAs were dramatically affected depending on the growth phase and the presence of vancomycin, whereas much less variations were found in the pool of cellular RNAs of the parent cells. Moreover, the RNA abundance pattern differed between EVs and EV-producing cells according to the growth conditions. Altogether, our findings show that the environment shapes the RNA cargo of the S. aureus EVs. Although the composition of EVs is impacted by the physiological state of the producing cells, our findings suggest a selective packaging of RNAs into EVs, as proposed for EV protein cargo. Our study shedds light to the possible roles of potentially functional RNAs in S. aureus EVs, notably in host-pathogen interactions.

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Section: Discussionmentioning

confidence: 99%

Environmental Plasticity of the RNA Content of Staphylococcus aureus Extracellular Vesicles

et al. 2021

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“…By sequestering the Hfq protein when the preferred carbon source is exhausted, CrcZ prevents Hfq-mediated translational repression of OprP, another porin involved in carbapenem entry. Other studies have emphasized the role of sRNAs in P. aeruginosa and other Enterobacteriaceae, and are summarized in a recent review ( Mediati et al, 2021 ).…”

Section: Srna Regulation Is Required For a Variety Of Biological Functionsmentioning

confidence: 99%

Diversity and Versatility in Small RNA-Mediated Regulation in Bacterial Pathogens

Felden

Augagneur

2021

Front. Microbiol.

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Bacterial gene expression is under the control of a large set of molecules acting at multiple levels. In addition to the transcription factors (TFs) already known to be involved in global regulation of gene expression, small regulatory RNAs (sRNAs) are emerging as major players in gene regulatory networks, where they allow environmental adaptation and fitness. Developments in high-throughput screening have enabled their detection in the entire bacterial kingdom. These sRNAs influence a plethora of biological processes, including but not limited to outer membrane synthesis, metabolism, TF regulation, transcription termination, virulence, and antibiotic resistance and persistence. Almost always noncoding, they regulate target genes at the post-transcriptional level, usually through base-pair interactions with mRNAs, alone or with the help of dedicated chaperones. There is growing evidence that sRNA-mediated mechanisms of actions are far more diverse than initially thought, and that they go beyond the so-called cis- and trans-encoded classifications. These molecules can be derived and processed from 5' untranslated regions (UTRs), coding or non-coding sequences, and even from 3' UTRs. They usually act within the bacterial cytoplasm, but recent studies showed sRNAs in extracellular vesicles, where they influence host cell interactions. In this review, we highlight the various functions of sRNAs in bacterial pathogens, and focus on the increasing examples of widely diverse regulatory mechanisms that might compel us to reconsider what constitute the sRNA.

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“…High-throughput RNA sequencing (RNAseq) has revolutionized the discovery of regulatory RNAs in bacteria [1][2][3][4][5][6][7][8][9][10][11][12][13]. These RNA regulators are mostly non-coding and usually synthesized under certain physiological conditions [3].…”

Section: Introductionmentioning

confidence: 99%

Specific and Global RNA Regulators in Pseudomonas aeruginosa

Pušić

Sonnleitner

Bläsi

2021

IJMS

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Pseudomonas aeruginosa (Pae) is an opportunistic pathogen showing a high intrinsic resistance to a wide variety of antibiotics. It causes nosocomial infections that are particularly detrimental to immunocompromised individuals and to patients suffering from cystic fibrosis. We provide a snapshot on regulatory RNAs of Pae that impact on metabolism, pathogenicity and antibiotic susceptibility. Different experimental approaches such as in silico predictions, co-purification with the RNA chaperone Hfq as well as high-throughput RNA sequencing identified several hundreds of regulatory RNA candidates in Pae. Notwithstanding, using in vitro and in vivo assays, the function of only a few has been revealed. Here, we focus on well-characterized small base-pairing RNAs, regulating specific target genes as well as on larger protein-binding RNAs that sequester and thereby modulate the activity of translational repressors. As the latter impact large gene networks governing metabolism, acute or chronic infections, these protein-binding RNAs in conjunction with their cognate proteins are regarded as global post-transcriptional regulators.

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Networks of Resistance: Small RNA Control of Antibiotic Resistance

Cited by 41 publications

References 79 publications

Environmental Plasticity of the RNA Content of Staphylococcus aureus Extracellular Vesicles

Environmental Plasticity of the RNA Content of Staphylococcus aureus Extracellular Vesicles

Diversity and Versatility in Small RNA-Mediated Regulation in Bacterial Pathogens

Specific and Global RNA Regulators in Pseudomonas aeruginosa

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