Skip to main content

Advertisement

  • Review
  • Open Access

Secretory and circulating bacterial small RNAs: a mini-review of the literature

ExRNA20191:14

https://doi.org/10.1186/s41544-019-0015-z

  • Received: 22 June 2018
  • Accepted: 14 March 2019
  • Published:

Abstract

Background

Over the past decade, small non-coding RNAs (sRNAs) have been characterized as important post-transcriptional regulators in bacteria and other microorganisms. Secretable sRNAs from both pathogenic and non-pathogenic bacteria have been identified, revealing novel insight into interspecies communications. Recent advances in the understanding of the secretory sRNAs, including extracellular vesicle-transported sRNAs and circulating sRNAs, have raised great interest.

Methods

We performed a literature search of the database PubMed, surveying the present stage of knowledge in the field of secretory and circulating bacterial sRNAs.

Conclusion

Extracellular bacterial sRNAs play an active role in host-microbe interactions. The findings concerning the secretory and circulating bacterial sRNAs may kindle an eager interest in biomarker discovery for infectious bacterial diseases.

Keywords

  • Small non-coding RNA
  • Bacterial RNA
  • Secretory RNA
  • Outer membrane vesicle
  • Circulating biomarker

Background

Small non-coding RNAs (sRNAs) are a class of post-transcriptional regulators in bacteria and eukaryotes. Bacterial sRNAs usually refer to non-coding RNAs approximately 50–400 nt in length that are transcribed from intergenic regions of the bacterial genome [1]. The first characterized bacterial regulatory sRNA was MicF RNA from Escherichia coli, which can down-regulate the major outer membrane protein OmpF [2]. Since then, the abundance of bacterial sRNAs and their significance in physiological responses have been much better appreciated, due to the application of a combination of cloning-based techniques and computational methods [3, 4]. Integrated data concerning bacterial-specific sRNAs have contributed greatly to unveiling the regulatory networks of major bacterial pathogens [1, 5]. However, a main question that remains to be addressed is how study results should be translated into clinical benefits.

Interestingly, recent advances in the characterization of sRNA-containing microvesicles have provided important insights to this field of research. Extracellular sRNAs in membrane-enclosed vesicles represent a novel class of active players in host-microbe communications and potential circulating biomarkers for infectious diseases. In this review, we survey the current stage of knowledge concerning secretory sRNAs in pathogenic bacteria, their detection in the circulation, and discuss their potential clinical applications.

Bacterial sRNAs in extracellular vesicles

Secretory products of microorganisms play active roles in microbe-microbe and host-microbe communications. Extracellular vesicles (EVs) are major vehicles for secretory products in both bacteria and eukaryotes [6]. In Gram-negative bacteria, EVs usually go by the name “outer membrane vesicles (OMVs)”, which are generally produced by Gram-negative bacteria as part of their normal growth [7]. OMVs package a variety of bacterial products, including proteins, lipopolysaccharides (LPS), DNA fragments, and RNAs [7, 8]. OMVs were found to deliver virulence factors [911] and bacterial antigens within the human host [1214]. The roles of OMVs in immune modulation have been studied intensively [8]; however, the biological significance of bacterial RNAs in OMVs or those of other secreted factors remain largely undetermined.

In 2015, Ghosal et al. characterized the extracellular component of Escherichia coli, a model for Gram-negative bacteria [15]. The study demonstrated that the OMVs secreted by Escherichia coli substrain MG1655 contain abundant bacteria-derived, small non-coding RNAs. In the same year, Sjöström et al. reported that purified OMVs of Vibrio cholerae comprise sRNAs transcribed from intergenic regions [16]. To date, secretory sRNAs from a range of Gram-negative bacteria, including Pseudomonas aeruginosa, uropathogenic Escherichia coli strain 536, and Porphyromonas gingivalis, have been characterized in vitro [1720]. In addition, Resch et al. reported for the first time the identification of non-coding RNAs enriched in EVs (reported as membrane-derived vesicles, MVs) from Gram-positive bacteria, group A Streptococcus [21].

To date, secretory bacterial sRNAs remain much less understood compared to their well-documented intracellular counterparts. Their sorting mechanisms, cellular targets, and involvement in biological regulation are largely unknown. Recently, Koeppen et al. demonstrated that sRNA52320 from Pseudomonas aeruginosa OMVs can be transferred into airway epithelial cells, and may attenuate the LPS-induced immune response by targeting interleukin (IL)-8 mRNA [17]. This is the first description of inter-kingdom regulation by sRNAs via bacterial OMVs. The studies presented above have preliminarily revealed the biological and pathological significance of secretory bacterial sRNAs.

Characterization of secretory microRNA-sized sRNAs

Interestingly, recent studies have identified a distinct set of secretory sRNAs, microRNA (miRNA)-sized sRNAs (msRNAs), which are comparable in size (~ 22 nt) to eukaryotic miRNAs. First systemically characterized by Lee et al. in Streptococcus mutans, msRNAs were found to be expressed by diverse bacterial species [2225]. Recently, Choi et al. characterized secreted msRNAs in membrane vesicles from Gram-positive bacteria Streptococcus sanguinis, and in OMVs from three Gram-negative periodontal pathogens, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola [19]. They also found that OMVs may deliver specific msRNAs to recipient T cells and suppress the production of IL-5, IL-13, and IL-15. This phenomenon is similar to the exosome-mediated transfer of miRNAs in eukaryotes but is less commonly observed. In addition, Gu et al. identified the msRNA Sal-1 in Salmonella, a model intracellular bacterial pathogen [26]. Sal-1 shares a number of biological features with eukaryotic miRNAs and can be released into the cytoplasm of host epithelial cells. Sal-1 can target iNOS in a miRNA-like manner and is likely to facilitate the intracellular survival of Salmonella [27]. In conclusion, secretory msRNAs are a class of active players in host-microbe interactions that deserves more attention in future studies.

Identification of bacterial sRNAs in human circulation

Circulating RNAs, which have been intensively studied in recent years, consist of a wide range of RNA species, including miRNAs and other non-coding RNAs [28]. Over the past decade, circulating miRNAs have become a class of promising minimal-invasive biomarkers for cancers and other diseases [29, 30]. It is remarkable that cell-free exogenous RNAs, including miRNAs encoded by DNA viruses [31, 32], sRNAs from parasites [33, 34], and plant- and food-derived RNAs [3537], were also readily detected in the human circulation. However, expression profiling of bacterial sRNAs in circulation, especially for pathogen-encoded sRNAs in patients with infectious diseases, has not been systemically investigated.

In 2012, Wang et al. studied host-microbiome interaction by analyzing plasma RNAs originating from exogenous species in detail using a next-generation sequencing technique [38]. The results showed that a significant amount of the reads were mapped to diverse microbial species, including phylum Firmicutes, a major bacteria phylum present in the human gut microbiome. Semenov et al. also stably detected sRNAs matching bacterial non-coding RNAs attributed to the genera Escherichia and Acinetobacter as well as other microorganisms in plasma from healthy donors [39]. Subsequently, Beatty et al. conducted a detailed study analyzing the expression of circulating exogenous sRNAs from 6 participants, which showed that the majority of the bacterial reads were from phylum Proteobacteria, indicating that their origin was the gut [36]. Another recent study assessing cell-free RNAs in the circulation of pregnant women has also drawn a similar conclusion [40]. The studies presented above suggest that sRNAs that originate from the gut microbiome are likely to be a main constituent of the circulating “bacterial footprints” under physiologic conditions.

Expression profiling of disease-associated bacterial sRNAs in vivo has yet to be systematically studied. However, several recent studies have helped to gain further insight into this field of research. Fu et al. conducted a series of experiments to identify the sRNAs secreted by Mycobacterium tuberculosis (MTB) [41]. Four sRNAs previously characterized by Arnvig et al., including ASdes, ASpks, AS1726, and AS1890, were readily detected in the supernatant of cultured MTB using quantitative polymerase chain reaction (qPCR) assays [42]. Interestingly, the sRNA ASdes was also detected in the plasma of patient with active tuberculosis; the detection rate was 55.56% (15/27). This inspiring discovery suggests that cell-free bacteria-specific sRNAs can be released into the circulation, possibly from infected tissues. Notably, tuberculosis is known for a lack of early-stage diagnostic biomarkers. To our knowledge, a plethora of MTB-encoded sRNAs have been identified previously [4246]; therefore, further investigations regarding the secretion of bacterial sRNAs may provide novel insight into the discovery of sRNA-based biomarker for tuberculosis and other bacterial infectious diseases. However, more questions concerning the secretory mechanisms and the tissues of origin of circulating bacterial sRNAs remain to be answered.

Conclusions

Recent extensive studies have unveiled novel aspects regarding the identification (Table 1) and the biological activities (Fig. 1) of secretory bacterial sRNAs, which have drawn increasing attention. First, the massive datasets obtained using deep-sequencing techniques and bioinformatics have shown that regulatory sRNAs can be transferred to host cells via membrane-enclosed vesicles from both Gram-negative and Gram-positive bacteria, representing a class of cross-species virulence factors of bacterial pathogenicity. Second, bacterial miRNA-sized sRNAs analogous to eukaryotic miRNAs were found to be secreted as active players in host-microbe interactions. Finally, accumulating evidence suggests that blood circulation is the interface between the host and microbiome under physiological and pathological conditions; therefore, bacterial sRNAs released into the circulation may be active players in, and even diagnostic biomarkers for, related diseases. Much like circulating miRNAs as biomarkers for cancer, the detection of circulating bacterial sRNAs should undergo rigorous investigation; however, the findings may kindle an eager interest in biomarker discovery for infectious bacterial diseases that are difficult to diagnose in the early stages.
Table 1

A summary of the reviewed studies on secretory bacterial sRNAs

Origin

Secretion

Remark

Reference

Escherichia coli substrain MG1655

OMVs

The first detailed study on the secretory sRNA of Escherichia coli

[15]

Vibrio cholerae

OMVs

Transcribed from intergenic regions

[16]

Pseudomonas aeruginosa

OMVs

sRNA52320 targets host’s immune response gene

[17]

Uropathogenic Escherichia coli strain 536

OMVs

sRNAs can be transferred into epithelial cells

[18]

Group A Streptococcus

MVs

From Gram-positive bacteria, miRNA-sized

[21]

Streptococcus sanguinis

MVs

From Gram-positive bacteria, miRNA-sized

[25]

Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola

OMVs

From periodontal pathogens, miRNA-sized

[19]

Salmonella

Undetermined

Sal-1 targets iNOS in a miRNA-like manner

[26, 27]

Phylum Firmicutes

Circulation

Gut microbiome

[38]

Genera Escherichia and Acinetobacter

Circulation

Gut microbiome

[39]

Phylum Proteobacteria

Circulation

Gut microbiome

[36]

Mycobacterium tuberculosis

Culture supernatant and circulation

ASdes is detectable in the plasma from active tuberculosis patients

[41]

Fig. 1
Fig. 1

The biological activities of secretory bacterial sRNAs. A. Bacterial sRNAs can be sorted into the OMVs in Gram-negative bacteria or MVs in Gram-positive bacteria; B. sRNAs carried by OMVs/MVs can be released into the extracellular space, taken up by recipient cells, and repress host mRNAs; C. Secretory bacterial sRNAs are detectable in the circulation of infected host; however, the mechanisms remain largely unknown

Abbreviations

EV: 

extracellular vesicle

IL: 

interleukin

LPS: 

lipopolysaccharides

miRNA: 

microRNA

msRNA: 

microRNA-sized small non-coding RNA

MTB: 

Mycobacterium tuberculosis

MV: 

membrane-derived vesicle

OMV: 

outer membrane vesicle

qPCR: 

quantitative polymerase chain reaction

sRNA: 

small non-coding RNA

Declarations

Acknowledgements

Not applicable.

Funding

This work is supported by a grant from the National Natural Science Foundation of China (No. 81741118).

Availability of data and materials

Not applicable.

Authors’ contributions

Y.W and J. F collected the data. J. F wrote the manuscript. Both authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150086, China

References

  1. Nitzan M, Rehani R, Margalit H. Integration of bacterial small RNAs in regulatory networks. Annu Rev Biophys. 2017;46:131–48.View ArticleGoogle Scholar
  2. Mizuno T, Chou MY, Inouye M. A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc Natl Acad Sci U S A. 1984;81:1966–70.View ArticleGoogle Scholar
  3. Gomez-Lozano M, Marvig RL, Molin S, Long KS. Identification of bacterial small RNAs by RNA sequencing. Methods Mol Biol. 2014;1149:433–56.View ArticleGoogle Scholar
  4. Wang J, Rennie W, Liu C, Carmack CS, Prevost K, Caron MP, Masse E, Ding Y, Wade JT. Identification of bacterial sRNA regulatory targets using ribosome profiling. Nucleic Acids Res. 2015;43:10308–20.PubMedPubMed CentralGoogle Scholar
  5. Bourqui R, Dutour I, Dubois J, Benchimol W, Thebault P. rNAV 2.0: a visualization tool for bacterial sRNA-mediated regulatory networks mining. BMC Bioinformatics. 2017;18:188.View ArticleGoogle Scholar
  6. van der Pol E, Boing AN, Harrison P, Sturk A, Nieuwland R. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev. 2012;64:676–705.View ArticleGoogle Scholar
  7. Pathirana RD, Kaparakis-Liaskos M. Bacterial membrane vesicles: biogenesis, immune regulation and pathogenesis. Cell Microbiol. 2016;18:1518–24.View ArticleGoogle Scholar
  8. Kaparakis-Liaskos M, Ferrero RL. Immune modulation by bacterial outer membrane vesicles. Nat Rev Immunol. 2015;15:375–87.View ArticleGoogle Scholar
  9. Yokoyama K, Horii T, Yamashino T, Hashikawa S, Barua S, Hasegawa T, Watanabe H, Ohta M. Production of Shiga toxin by Escherichia coli measured with reference to the membrane vesicle-associated toxins. FEMS Microbiol Lett. 2000;192:139–44.View ArticleGoogle Scholar
  10. Dutta S, Iida K, Takade A, Meno Y, Nair GB, Yoshida S. Release of Shiga toxin by membrane vesicles in Shigella dysenteriae serotype 1 strains and in vitro effects of antimicrobials on toxin production and release. Microbiol Immunol. 2004;48:965–9.View ArticleGoogle Scholar
  11. MacDonald IA, Kuehn MJ. Offense and defense: microbial membrane vesicles play both ways. Res Microbiol. 2012;163:607–18.View ArticleGoogle Scholar
  12. Chen DJ, Osterrieder N, Metzger SM, Buckles E, Doody AM, DeLisa MP, Putnam D. Delivery of foreign antigens by engineered outer membrane vesicle vaccines. Proc Natl Acad Sci U S A. 2010;107:3099–104.View ArticleGoogle Scholar
  13. Fantappie L, de Santis M, Chiarot E, Carboni F, Bensi G, Jousson O, Margarit I, Grandi G. Antibody-mediated immunity induced by engineered Escherichia coli OMVs carrying heterologous antigens in their lumen. J Extracell Vesicles. 2014;3.Google Scholar
  14. Hickey CA, Kuhn KA, Donermeyer DL, Porter NT, Jin C, Cameron EA, Jung H, Kaiko GE, Wegorzewska M, Malvin NP, Glowacki RW, Hansson GC, Allen PM, Martens EC, Stappenbeck TS. Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles. Cell Host Microbe. 2015;17:672–80.View ArticleGoogle Scholar
  15. Ghosal A, Upadhyaya BB, Fritz JV, Heintz-Buschart A, Desai MS, Yusuf D, Huang D, Baumuratov A, Wang K, Galas D, Wilmes P. The extracellular RNA complement of Escherichia coli. Microbiologyopen. 2015.Google Scholar
  16. Sjostrom AE, Sandblad L, Uhlin BE, Wai SN. Membrane vesicle-mediated release of bacterial RNA. Sci Rep. 2015;5:15329.View ArticleGoogle Scholar
  17. Koeppen K, Hampton TH, Jarek M, Scharfe M, Gerber SA, Mielcarz DW, Demers EG, Dolben EL, Hammond JH, Hogan DA, Stanton BA. A novel mechanism of host-pathogen interaction through sRNA in bacterial outer membrane vesicles. PLoS Pathog. 2016;12:e1005672.View ArticleGoogle Scholar
  18. Blenkiron C, Simonov D, Muthukaruppan A, Tsai P, Dauros P, Green S, Hong J, Print CG, Swift S, Phillips AR. Uropathogenic Escherichia coli releases extracellular vesicles that are associated with RNA. PLoS One. 2016;11:e0160440.View ArticleGoogle Scholar
  19. Choi JW, Kim SC, Hong SH, Lee HJ. Secretable small RNAs via outer membrane vesicles in periodontal pathogens. J Dent Res. 2017;96:458–66.View ArticleGoogle Scholar
  20. Ho MH, Chen CH, Goodwin JS, Wang BY, Xie H. Functional advantages of Porphyromonas gingivalis vesicles. PLoS One. 2015;10:e0123448.View ArticleGoogle Scholar
  21. Resch U, Tsatsaronis JA, Le Rhun A, Stubiger G, Rohde M, Kasvandik S, Holzmeister S, Tinnefeld P, Wai SN, Charpentier E. A two-component regulatory system impacts extracellular membrane-derived vesicle production in group a Streptococcus. MBio. 2016;7.Google Scholar
  22. Lee HJ, Hong SH. Analysis of microRNA-size, small RNAs in Streptococcus mutans by deep sequencing. FEMS Microbiol Lett. 2012;326:131–6.View ArticleGoogle Scholar
  23. Kang SM, Choi JW, Lee Y, Hong SH, Lee HJ. Identification of microRNA-size, small RNAs in Escherichia coli. Curr Microbiol. 2013;67:609–13.View ArticleGoogle Scholar
  24. Mao MY, Yang YM, Li KZ, Lei L, Li M, Yang Y, Tao X, Yin JX, Zhang R, Ma XR, Hu T. The rnc gene promotes exopolysaccharide synthesis and represses the vicRKX gene expressions via MicroRNA-size small RNAs in Streptococcus mutans. Front Microbiol. 2016;7:687.View ArticleGoogle Scholar
  25. Choi JW, Kwon TY, Hong SH, Lee HJ. Isolation and characterization of a microRNA-size Secretable small RNA in Streptococcus sanguinis. Cell Biochem Biophys. 2018;76:293–301.View ArticleGoogle Scholar
  26. Gu H, Zhao C, Zhang T, Liang H, Wang XM, Pan Y, Chen X, Zhao Q, Li D, Liu F, Zhang CY, Zen K. Salmonella produce microRNA-like RNA fragment Sal-1 in the infected cells to facilitate intracellular survival. Sci Rep. 2017;7:2392.View ArticleGoogle Scholar
  27. Zhao C, Zhou Z, Zhang T, Liu F, Zhang CY, Zen K, Gu H. Salmonella small RNA fragment Sal-1 facilitates bacterial survival in infected cells via suppressing iNOS induction in a microRNA manner. Sci Rep. 2017;7:16979.View ArticleGoogle Scholar
  28. Zen K, Zhang CY. Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev. 2012;32:326–48.View ArticleGoogle Scholar
  29. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.View ArticleGoogle Scholar
  30. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.View ArticleGoogle Scholar
  31. Li S, Zhu J, Zhang W, Chen Y, Zhang K, Popescu LM, Ma X, Lau WB, Rong R, Yu X, Wang B, Li Y, Xiao C, Zhang M, Wang S, Yu L, Chen AF, Yang X, Cai J. Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation. 2011;124:175–84.View ArticleGoogle Scholar
  32. Liang Q, Wang K, Wang B, Cai Q. HCMV-encoded miR-UL112-3p promotes glioblastoma progression via tumour suppressor candidate 3. Sci Rep. 2017;7:44705.View ArticleGoogle Scholar
  33. Hoy AM, Lundie RJ, Ivens A, Quintana JF, Nausch N, Forster T, Jones F, Kabatereine NB, Dunne DW, Mutapi F, Macdonald AS, Buck AH. Parasite-derived microRNAs in host serum as novel biomarkers of helminth infection. PLoS Negl Trop Dis. 2014;8:e2701.View ArticleGoogle Scholar
  34. Quintana JF, Makepeace BL, Babayan SA, Ivens A, Pfarr KM, Blaxter M, Debrah A, Wanji S, Ngangyung HF, Bah GS, Tanya VN, Taylor DW, Hoerauf A, Buck AH. Extracellular Onchocerca-derived small RNAs in host nodules and blood. Parasit Vectors. 2015;8:58.View ArticleGoogle Scholar
  35. Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen J, Wang J, Wang M, Zhang Q, Zhang J, Zen K, Zhang CY. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res. 2012;22:107–26.View ArticleGoogle Scholar
  36. Beatty M, Guduric-Fuchs J, Brown E, Bridgett S, Chakravarthy U, Hogg RE, Simpson DA. Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma. BMC Genomics. 2014;15:933.View ArticleGoogle Scholar
  37. Shu J, Chiang K, Zempleni J, Cui J. Computational characterization of exogenous MicroRNAs that can be transferred into human circulation. PLoS One. 2015;10:e0140587.View ArticleGoogle Scholar
  38. Wang K, Li H, Yuan Y, Etheridge A, Zhou Y, Huang D, Wilmes P, Galas D. The complex exogenous RNA spectra in human plasma: an interface with human gut biota? PLoS One. 2012;7:e51009.View ArticleGoogle Scholar
  39. Semenov DV, Baryakin DN, Brenner EV, Kurilshikov AM, Vasiliev GV, Bryzgalov LA, Chikova ED, Filippova JA, Kuligina EV, Richter VA. Unbiased approach to profile the variety of small non-coding RNA of human blood plasma with massively parallel sequencing technology. Expert Opin Biol Ther. 2012;12(Suppl 1):S43–51.View ArticleGoogle Scholar
  40. Pan W, Ngo TTM, Camunas-Soler J, Song CX, Kowarsky M, Blumenfeld YJ, Wong RJ, Shaw GM, Stevenson DK, Quake SR. Simultaneously monitoring immune response and microbial infections during pregnancy through plasma cfRNA sequencing. Clin Chem. 2017;63:1695–704.View ArticleGoogle Scholar
  41. Fu Y, Li W, Wu Z, Tao Y, Wang X, Wei J, Jiang P, Wu J, Zhang Z, Zhang W, Zhao J, Zhang F. Detection of mycobacterial small RNA in the bacterial culture supernatant and plasma of patients with active tuberculosis. Biochem Biophys Res Commun. 2018.Google Scholar
  42. Arnvig KB, Young DB. Identification of small RNAs in mycobacterium tuberculosis. Mol Microbiol. 2009;73:397–408.View ArticleGoogle Scholar
  43. Arnvig KB, Comas I, Thomson NR, Houghton J, Boshoff HI, Croucher NJ, Rose G, Perkins TT, Parkhill J, Dougan G, Young DB. Sequence-based analysis uncovers an abundance of non-coding RNA in the total transcriptome of mycobacterium tuberculosis. PLoS Pathog. 2011;7:e1002342.View ArticleGoogle Scholar
  44. Pellin D, Miotto P, Ambrosi A, Cirillo DM, Di Serio C. A genome-wide identification analysis of small regulatory RNAs in mycobacterium tuberculosis by RNA-Seq and conservation analysis. PLoS One. 2012;7:e32723.View ArticleGoogle Scholar
  45. Miotto P, Forti F, Ambrosi A, Pellin D, Veiga DF, Balazsi G, Gennaro ML, Di Serio C, Ghisotti D, Cirillo DM. Genome-wide discovery of small RNAs in mycobacterium tuberculosis. PLoS One. 2012;7:e51950.View ArticleGoogle Scholar
  46. Tsai CH, Baranowski C, Livny J, McDonough KA, Wade JT, Contreras LM. Identification of novel sRNAs in mycobacterial species. PLoS One. 2013;8:e79411.View ArticleGoogle Scholar

Copyright

© The Author(s) 2019

Advertisement