Small Non-coding RNA RyhB Mediates Persistence to Multiple Antibiotics and Stresses in Uropathogenic Escherichia coli by Reducing Cellular Metabolism

Zhang, Shanshan; Liu, Shuang; Wu, Nan; Yuan, Youhua; Zhang, Wenhong; Zhang, Ying

doi:10.3389/fmicb.2018.00136

Cited by 22 publications

(22 citation statements)

References 40 publications

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“…A most spectacular case is represented by the role RyhB could play in the bacterial persistence of uropathogenic E . coli to different classes of antibiotics, among which gentamicin [43]. Persistence is a phenomenon in which a fraction of the bacterial population enters a metabolically inactive state that enables it to survive exposure to bactericidal antibiotics [44].…”

Section: Discussionmentioning

confidence: 99%

A small RNA controls bacterial sensitivity to gentamicin during iron starvation

2019

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Phenotypic resistance describes a bacterial population that becomes transiently resistant to an antibiotic without requiring a genetic change. We here investigated the role of the small regulatory RNA (sRNA) RyhB, a key contributor to iron homeostasis, in the phenotypic resistance of Escherichia coli to various classes of antibiotics. We found that RyhB induces phenotypic resistance to gentamicin, an aminoglycoside that targets the ribosome, when iron is scarce. RyhB induced resistance is due to the inhibition of respiratory complexes Nuo and Sdh activities. These complexes, which contain numerous Fe-S clusters, are crucial for generating a proton motive force (pmf) that allows gentamicin uptake. RyhB regulates negatively the expression of nuo and sdh , presumably by binding to their mRNAs and, as a consequence, inhibiting their translation. We further show that Isc Fe-S biogenesis machinery is essential for the maturation of Nuo. As RyhB also limits levels of the Isc machinery, we propose that RyhB may also indirectly impact the maturation of Nuo and Sdh. Notably, our study shows that respiratory complexes activity levels are predictive of the bacterial sensitivity to gentamicin. Altogether, these results unveil a new role for RyhB in the adaptation to antibiotic stress, an unprecedented consequence of its role in iron starvation stress response.

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Section: Discussionmentioning

confidence: 99%

A small RNA controls bacterial sensitivity to gentamicin during iron starvation

2019

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“…A single sRNA can regulate the fate of several target mRNAs via partial base pairing, thereby fine-tuning pathways involved in metabolism [ 19 ], quorum sensing [ 20 ], antibiotic resistance [ 21 ], stress response [ 22 ], or virulence [ 23 ]. For instance, ryhB appears to aid persister cell formation in uropathogenic E. coli [ 24 ], while this sRNA has been previously reported to regulate iron metabolism [ 25 ]. This further illustrates the intricate nature of RNA regulatory networks in bacteria.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome-Wide Analysis of Stationary Phase Small ncRNAs in E. coli

Raad

Luidalepp

Fasnacht

et al. 2021

IJMS

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Almost two-thirds of the microbiome’s biomass has been predicted to be in a non-proliferating, and thus dormant, growth state. It is assumed that dormancy goes hand in hand with global downregulation of gene expression. However, it remains largely unknown how bacteria manage to establish this resting phenotype at the molecular level. Recently small non-protein-coding RNAs (sRNAs or ncRNAs) have been suggested to be involved in establishing the non-proliferating state in bacteria. Here, we have deep sequenced the small transcriptome of Escherichia coli in the exponential and stationary phases and analyzed the resulting reads by a novel biocomputational pipeline STARPA (Stable RNA Processing Product Analyzer). Our analysis reveals over 12,000 small transcripts enriched during both growth stages. Differential expression analysis reveals distinct sRNAs enriched in the stationary phase that originate from various genomic regions, including transfer RNA (tRNA) fragments. Furthermore, expression profiling by Northern blot and RT-qPCR analyses confirms the growth phase-dependent expression of several enriched sRNAs. Our study adds to the existing repertoire of bacterial sRNAs and suggests a role for some of these small molecules in establishing and maintaining stationary phase as well as the bacterial stress response. Functional characterization of these detected sRNAs has the potential of unraveling novel regulatory networks central for stationary phase biology.

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“…A most spectacular case is represented by the role RyhB could play in the bacterial persistence of uropathogenic E. coli to different classes of antibiotics, among which included gentamicin (40). Persistence is a phenomenon in which a fraction of the bacterial population enters a metabolically inactive state that enables it to survive exposure to bactericidal antibiotics (41).…”

Section: Discussionmentioning

confidence: 99%

A small RNA controls bacterial resistance to gentamicin during iron starvation

Chareyre

Barras

Mandin

2018

Preprint

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19Phenotypic resistance describes a bacterial population that becomes 20 transiently resistant to an antibiotic without requiring a genetic change. We here 21 investigated the role of the small regulatory RNA (sRNA) RyhB, a key contributor to 22 iron homeostasis, in the phenotypic resistance of Escherichia coli to various classes 23 of antibiotics. We found that RyhB induces resistance to gentamicin, an 24 aminoglycoside that targets the ribosome, when iron is scarce. RyhB induced 25 resistance is due to the inhibition of respiratory complexes Nuo and Sdh activities. 26 These complexes, which contain numerous Fe-S clusters, are crucial for generating a 27 proton motive force (pmf) that allows gentamicin uptake. RyhB directly represses the 28 expression of nuo and sdh operons by binding to their mRNAs, thereby inhibiting their 29 translation. Indirectly, RyhB also inhibits the maturation of Nuo and Sdh by repressing 30 synthesis of the Isc Fe-S biogenesis machinery. Notably, our study identifies nuo as a 31 new direct RyhB target and shows that respiratory complexes activity levels are 32 predictive of the bacterial sensitivity to gentamicin. Altogether, these results unveil a 33 new role for RyhB in the adaptation to antibiotic stress, an unprecedented 34 consequences of its role in iron starvation stress response. 35 36 3 37 AUTHOR'S SUMMARY 38 Understanding the mechanisms at work behind bacterial antibiotic resistance has 39 become a major health issue in the face of the antibiotics crisis. Here, we show that 40 RyhB, a bacterial small regulatory RNA, induces resistance of Escherichia coli to the 41 antibiotic gentamicin when iron is scarce, an environmental situation prevalent during 42 host-pathogen interactions. This resistance is due to RyhB repression of the 43 synthesis and post-translational maturation of the respiratory complexes Nuo and 44Sdh. These complexes are crucial in producing the proton motive force that allows 45 uptake of the antibiotics in the cell. Altogether, these data point out to a major role for 46 RyhB in escaping antibacterial action. 47 71 5 enhances resistance to aminoglycosides, a well-known class of antibiotics that target 72 the ribosome (7). This resistance is due to a deficiency in the maturation of the 73 respiratory complexes in isc mutants, which in turn leads to a decrease in the proton 74 motive force (pmf) that is essential for aminoglycosides uptake (15). Incidentally, it 75 was deduced from these results that the Suf machinery is unable to maturate 76 efficiently the Fe-S cluster containing proteins of the respiratory complexes, although 77 the molecular reason for this still remains unclear. Overall this study predicted that an 78 environmental signal that induces the switch from Isc to Suf should induce a transient 79 resistance to aminoglycosides. 80 Iron starvation is one signal that decreases the expression of the isc operon 81 encoding the Isc pathway. The small RNA RyhB mediates this regulation.(16). RyhB 82 is one of the most studied sRNAs to date in E...

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Small Non-coding RNA RyhB Mediates Persistence to Multiple Antibiotics and Stresses in Uropathogenic Escherichia coli by Reducing Cellular Metabolism

Cited by 22 publications

References 40 publications

A small RNA controls bacterial sensitivity to gentamicin during iron starvation

A small RNA controls bacterial sensitivity to gentamicin during iron starvation

Transcriptome-Wide Analysis of Stationary Phase Small ncRNAs in E. coli

A small RNA controls bacterial resistance to gentamicin during iron starvation

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