Skip to content

Advertisement

Open Access

Complete genome sequence of Lactobacillus rhamnosus Pen, a probiotic component of a medicine used in prevention of antibiotic-associated diarrhoea in children

  • Piotr Jarocki1Email authorView ORCID ID profile,
  • Marcin Podleśny1, 2,
  • Mariusz Krawczyk3,
  • Agnieszka Glibowska1,
  • Jarosław Pawelec4,
  • Elwira Komoń-Janczara1,
  • Oleksandr Kholiavskyi1,
  • Michał Dworniczak1 and
  • Zdzisław Targoński1
Gut Pathogens201810:5

https://doi.org/10.1186/s13099-018-0235-z

Received: 26 January 2018

Accepted: 20 February 2018

Published: 22 February 2018

Abstract

Background

Lactobacillus rhamnosus Pen is a human endogenous strain with well-documented health promoting properties that is used for production of probiotics. It has a long safety history of application, and its effectiveness in the prevention of antibiotic-associated diarrhoea has also been confirmed in clinical trials.

Results

Here we present the complete genome sequence of L. rhamnosus Pen, which consists of a circular 2,884,4966-bp chromosome with a GC content of 46.8%. Within 2907 open reading frames (ORFs), genes involved with probiotic properties were identified. A CRISPR locus, consisting of a 1092-nt region with 16 spacers, was also detected. Finally, an intact prophage of ~ 40.7 kb, 57 ORFs, GC content 44.8% was identified.

Conclusions

Genomic analysis confirmed the probiotic properties of L. rhamnosus Pen and may indicate new biotechnological applications of this industrially important strain.

Keywords

Lactobacillus rhamnosus PenProbioticsGenome sequenceCRISPR–Cas locusProphage

Introduction

Lactobacillus rhamnosus has been isolated from the human intestinal tract, oral cavity, and vagina. Owing to their beneficial effects on human health, many strains of L. rhamnosus are also used in the dairy and pharmaceutical industries. Examples of such industrially important probiotic strains are Lactobacillus rhamnosus GG and Lactobacillus rhamnosus R0011, as well as Lactobacillus rhamnosus Pen, which is a component of a medicine commonly used to reduce the risk of diarrhoea development during antibiotic therapy [13]. Many characteristics of strain Pen have previously been reported, including carbohydrate utilisation, colony and cell morphology, antibiotic sensitivity, RAPD patterns, and SDS-PAGE and two-dimensional (2D) electrophoretic profiles of surface-associated proteins [4, 5]. Other properties, such as adhesion ability [6], survival rate in acidic pH [7], antiradical activity [8] and production of extracellular ferulic acid esterase [9] have also been analysed. Optimisation of medium composition to enhance growth of L. rhamnosus Pen using response surface methodology was reported by Polak-Berecka et al. [10].

Methods

Genomic DNA was isolated and purified using a Genomic Mini AX Bacteria + kit (A&A Biotechnology, Gdynia, Poland); DNA concentration was determined using a NanoDrop spectrophotometer (Thermo Scientific, Waltham, USA). Sequencing was performed at Genomed SA. Briefly, a paired-end library was constructed by using the NEB-Next® DNA Library Prep Master Mix Set for Illumina (NEB, Ipswich, USA) and subsequently sequenced on an Illumina MiSeq with 2 × 250 paired end sequencing chemistry (Illumina, San Diego, USA). Additionally, a 5–8 kb mate-pair library was constructed according protocol developed in BGI (Shenzhen, China) and sequenced on a HiSeq 4000 with 2 × 100 paired end sequencing chemistry (Illumina, San Diego, USA). A total of 1,270,358,608 bases and 362,759,422 paired reads were yielded. Read trimming and filtering was performed using Cutadapt 1.9.1 [11]. De novo assembly was conducted using SPAdes 3.1.1. [12], which yielded one major contig with 679-fold average coverage. Functional annotation of predicted genes was performed using the NCBI Prokaryotic Genome Annotation Pipeline [13]. The clusters of orthologous groups (COGs) of proteins were determined using eggNOG 4.5 [14]. Ribosomal RNA genes were detected using RNAmer 1.2 [15] and tRNA genes were identified using tRNAscan-SE v. 2.0 [16]. Sequences of proteins which may determine putative probiotic properties of L. rhamnosus Pen were individually search against Conserved Domains Database (NCBI) [17] and InterPro detabase (EMBL-EBI) [18]. Genes potentially involved in the biosynthesis of bacteriocins were identified using BAGEL [19]. The presence of antibiotic resistance genes was tested using ResFinder [20]. Phaster was used to search for prophage sequences [21] and the presence of a CRISPR/Cas system was predicted using CRISPRs finder [22] and the Crispr Recognition Tool [23]. Genome mapping and alignment visualisation were performed using CGView [24] and BRIG [25] respectively.

Quality assurance

Genomic DNA used for sequencing was isolated from a pure culture of a single bacterial isolate of Lactobacillus rhamnosus Pen (Additional file 1: Figure S1). Additionally, the 16S rRNA gene sequence was determined and compared against NCBI database using BLAST (Additional file 2: Figure S2).

Results and discussion

The complete genome of L. rhamnosus Pen consists of a 2,884,966-nt circular chromosome (GC content of 46.8%) with no plasmid. Among the 2907 identified open reading frames, 2729 contain protein-coding genes. In addition, 59 tRNA genes, 5 rRNA operons, and 101 pseudogenes were identified (Table 1, Additional file 3: Figure S3). Of the identified coding sequences, 2422 (88.7%) were grouped into 20 COG classes. Coding sequences were identified as being involved in carbohydrate transport and metabolism (12%), transcription (7.3%), amino acid transport and metabolism (6.9%), translation, ribosomal structure and biogenesis (5.4%), and replication, recombination and repair of nucleic acids (4.8%) (Table 2, Additional file 3: Figure S3). Comparison of the L. rhamnosus Pen genome with eleven other L. rhamnosus complete genome sequences showed the highest similarity with intestinal isolate L. rhamnosus LOCK900 (symmetric identity 98.76%, gapped identity 99.97; CP005484.1) [26] and substantially lower sequence similarity with the industrially important L. rhamnosus GG (symmetric identity 84.24%, gapped identity 97.50%; AP011548.1) [27] (Fig. 1).
Table 1

General features of Lactobacillus rhamnosus Pen genome

Attribute

Value

Genome size (bp)

2,884,966

Contig numbers

1

DNA G+C (%)

46.8

Total genes

2907

Protein-coding genes

2729

rRNA genes

15

tRNA genes

59

ncRNA genes

3

Pseudogenes

101

Plasmid

0

Prophages

1

CRISPR arrays

1

GenBank accession

CP020464.1

Table 2

COG functional categories of Lactobacillus rhamnosus Pen genome

#COG class

Description

Count

%

Information storage and processing

 [J]

Translation, ribosomal structure and biogenesis

153

5.4

 [A]

RNA processing and modification

0

0.0

 [K]

Transcription

208

7.3

 [L]

Replication, recombination and repair

135

4.8

 [B]

Chromatin structure and dynamics

0

0.0

Cellular processes and signaling

 [D]

Cell cycle control, cell division, chromosome partitioning

34

1.2

 [Y]

Nuclear structure

0

0.0

 [V]

Defense mechanisms

101

3.6

 [T]

Signal transduction mechanisms

97

3.4

 [M]

Cell wall/membrane/envelope biogenesis

130

4.6

 [N]

Cell motility

9

0.3

 [Z]

Cytoskeleton

0

0.0

 [W]

Extracellular structures

0

0.0

 [U]

Intracellular trafficking, secretion, and vesicular transport

23

0.8

 [O]

Posttranslational modification, protein turnover, chaperones

57

2.0

Metabolism

 [C]

Energy production and conversion

91

3.2

 [G]

Carbohydrate transport and metabolism

339

12.0

 [E]

Amino acid transport and metabolism

195

6.9

 [F]

Nucleotide transport and metabolism

87

3.1

 [H]

Coenzyme transport and metabolism

57

2.0

 [I]

Lipid transport and metabolism

62

2.2

 [P]

Inorganic ion transport and metabolism

103

3.6

 [Q]

Secondary metabolites biosynthesis, transport and catabolism

27

1.0

Poorly characterized

 [R]

General function prediction only

303

10.7

 [S]

Function unknown

211

7.5

Fig. 1

Visualization of alignment of the Lactobacillus rhamnosus Pen genome with Lactobacillus rhamnosus LOCK900 and Lactobacillus rhamnosus GG complete genome sequences

Comparative genomic analysis of L. rhamnosus Pen showed the presence of numerous genes which may determine its putative probiotic properties, supporting use of the strain in prevention of various gastrointestinal disorders. Genetic factors involved in cell surface adherence, biofilm formation, and pathogen inhibition were identified (Additional file 4: Table S1). Such features are known to provide a survival advantage for probiotic strains and are important for effective bacterial colonisation of the human intestine [1, 2832]. Additionally, detailed analysis of the genome did not reveal transmissible antibiotic resistance genes in the chromosome of L. rhamnosus Pen. It was previously described that such genetic determinants may constitute a reservoir of antibiotic resistance for food and gut pathogens. On the other hand, presence of intrinsic antibiotic resistance among probiotic strains is valuable factor in restoring the intestinal microbiota after antibiotic treatment [33].

The analysis performed using CRISPRs finder and the Crispr Recognition Tool indicated that the genome contains one regularly interspaced short palindromic repeat locus consisting of a 1092-nt region with 16 spacers (30–31 nt in length) (Fig. 2). The detected CRISPR–Cas system is of type II-A/LsaI1 (four cas genes; cas1, cas2, cas9, csn2, and one CRISPR array), similar to previously described CRISPR loci characteristic of L. rhamnosus strains [34]. BLASTN searches comparing all 16 spacers against the phage and plasmid NCBI databases revealed no sequence identity with known mobile genetic elements of lactobacilli. In a previous report, Douillard et al. [29] observed that many spacer sequences of L. rhamnosus strains fully or partially matched sequenced bacteriophage genomes, such as Lactobacillus rhamnosus phage Lc-Nu and Lrm1, as well as L. casei phages, including φAT3, A2, and PL-1. This phenomenon suggests that CRISPR modules may play an important role in protection against different mobile elements and also provide specific bacteriophage resistance [35]. Interestingly, similar results were not obtained for the CRISPR locus identified for Lactobacillus rhamnosus Pen.
Fig. 2

CRISPR–Cas system architecture of selected Lactobacillus rhamnosus strains

Finally, one intact prophage of ~ 40.7 kb with a GC content of 44.8% was identified. This prophage sequence showed only 94% (query coverage 59%) and 91% (query coverage 21%) similarity with two previously described L. rhamnosus bacteriophages, Lrm1 (EU246945.1) and Lc-Nu (AY131267.2), respectively [36, 37]. However, nearly identical prophage sequences were detected in the genomes of L. rhamnosus CLS17 (NZ_JYCS01000023.1), L. rhamnosus B1 (NZ_NXEU01000011.1), and L. rhamnosus ASCC 3029 (NZ_MLJZ01000021.1). In our previous study, we described the release of phage particles by L. rhamnosus Pen [38]. Although the physiological role of continuous phage particle release in Lactobacillus is not evident, it may be beneficial for the bacterial host. It was previously suggested that such behaviour may enhance biofilm formation and promote horizontal gene transfer. On the other hand, by facilitating binding to human platelets, spontaneous prophage induction may also play an important role in bacterial virulence [39, 40]. Additionally, considering that such bacteriophages may be simultaneously released to the culture medium and that this phenomenon does not lead to complete lysis of the culture, microorganisms containing such phages may have high potential for application as safe food-grade vectors for presenting or producing various biological factors such as antigens, receptors, or virulence proteins [38, 41].

In conclusion, genomic analysis has confirmed the probiotic properties of L. rhamnosus Pen and may indicate new biotechnological applications of this industrially important strain. However, to understand the nature of the relationship between this probiotic bacterium and its phage, further studies for molecular and physiological characterisation of the released bacteriophage should be performed. We hope that future studies may further our knowledge of phage biology and shed new light on interactions between phages and bacteria.

Abbreviations

ORF: 

open reading frame

COG: 

cluster of orthologous groups

CRISPR: 

clustered regularly interspaced short palindromic repeats

Declarations

Authors’ contributions

Conceived and designed the experiments: PJ, MP, MK, ZT. Performed the experiments: PJ, MK, AG, JP, OK, MD. Analyzed the data: PJ, MK, EKJ. Contributed reagents/materials/analysis tools: PJ, MP, MK. Wrote the paper: PJ. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Availability of data and materials

The complete genome sequence of Lactobacillus rhamnosus Pen has been deposited in GenBank under Accession Number CP020464.1. L. rhamnosus Pen is available at the Institute of Biochemistry and Biophysics, The Polish Academy of Sciences under the Number 2593.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Not applicable.

Funding

This work was financially supported by the National Science Centre, Poland [Grant Numbers UMO-2013/09/N/NZ9/01617 and UMO-2016/23/D/NZ9/02661].

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 Biotechnology, Microbiology and Human Nutrition, University of Life Sciences in Lublin, Lublin, Poland
(2)
Process and Development Department, Grupa Azoty Zakłady Azotowe “Puławy” S.A, Puławy, Poland
(3)
Genomed SA, Warsaw, Poland
(4)
Laboratory of Electron Microscopy, Department of Comparative Anatomy and Anthropology, Maria Curie-Skłodowska University, Lublin, Poland

References

  1. Kankainen M, Paulin L, Tynkkynen S, von Ossowski I, Reunanen J, Partanen P, et al. Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human–mucus binding protein. Proc Natl Acad Sci USA. 2009;106:17193–8.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Foster LM, Tompkins TA, Dahl WJ. A comprehensive post-market review of studies on a probiotic product containing Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011. Benef Microb. 2011;2:319–34.View ArticleGoogle Scholar
  3. Ruszczyński M, Radzikowski A, Szajewska H. Clinical trial: Effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children. Aliment Pharmacol Ther. 2008;28:154–61.View ArticlePubMedGoogle Scholar
  4. Bardowski J, Górecki RK, Kryszewska A, Szmytkowska A. Charaterisation of three probiotic strains of Lactobacillus rhamnosus present in Lakcid. 3rd probiotics probiotics new foods. Rome: ATTI Abstracts; 2005. p. 157. http://www.probiotics-prebiotics-newfood.com/pdf/3rd_Probiotics_Prebiotics.pdf.
  5. Jarocki P, Podleśny M, Waśko A, Siuda A, Targoński Z. Differentiation of three Lactobacillus rhamnosus strains (E/N, Oxy, and Pen) by SDS-PAGE and two-dimensional electrophoresis of surface-associated proteins. J Microbiol Biotechnol. 2010;20:558–62.PubMedGoogle Scholar
  6. Polak-Berecka M, Waśko A, Paduch R, Skrzypek T, Sroka-Bartnicka A. The effect of cell surface components on adhesion ability of Lactobacillus rhamnosus. Antonie Van Leeuwenhoek, vol. 106. Springer International Publishing; 2014. p. 751–62. http://link.springer.com/10.1007/s10482-014-0245-x. Accessed 20 Dec 2017.
  7. Goderska K, Czarnecka M, Czarnecki Z. Survival rate of chosen Lactobacillus bacteria type in media of different pH. Electron J Polish Agric Univ. 2002;5:1–7.Google Scholar
  8. Skrzypczak K, Gustaw W, Waśko A. Selected technological and probiotic characteristics of strains of Lactobacillus helveticus species. Żywność.Nauka.Technologia.Jakość/Food Sci Technol Qual. 2015;5:61–72. http://pttz.org/zyw/wyd/czas/2015,5(102)/05_Skrzypczak.pdf.
  9. Szwajgier D, Jakubczyk A. Production of extracellular ferulic acid esterases by Lactobacillus strains using natural and synthetic carbon sources. Acta Sci Pol Technol Aliment. 2011;10:287–302. http://www.scopus.com/inward/record.url?eid=2-s2.0-79960115292&partnerID=40&md5=e837d16eb2e07436531b8320d321655d.
  10. Polak-Berecka M, Waśko A, Kordowska-Wiater M, Podleśny M, Targoński Z, Kubik-Komar A. Optimization of medium composition for enhancing growth of Lactobacillus rhamnosus Pen using response surface methodology. Polish J Microbiol. 2010;59:113–8.Google Scholar
  11. Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet Journal. 2011;17:10. http://journal.embnet.org/index.php/embnetjournal/article/view/200.
  12. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol. 2012;19:455–77. https://doi.org/10.1089/cmb.2012.0021.View ArticlePubMedPubMed CentralGoogle Scholar
  13. Tatusova T, DiCuccio M, Badretdin A, Chetvernin V, Ciufo S, Li W. Prokaryotic genome annotation pipeline. NCBI Handb. 2nd ed. National Center for Biotechnology Information (US); 2013. https://www.ncbi.nlm.nih.gov/books/NBK174280/. Accessed 20 Dec 2017.
  14. Huerta-Cepas J, Szklarczyk D, Forslund K, Cook H, Heller D, Walter MC, et al. EGGNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences. Nucleic Acids Res. 2016;44:D286–93.View ArticlePubMedGoogle Scholar
  15. Lagesen K, Hallin P, Rødland EA, Stærfeldt HH, Rognes T, Ussery DW. RNAmmer: consistent and rapid annotation of ribosomal RNA genes. Nucleic Acids Res. 2007;35:3100–8.View ArticlePubMedPubMed CentralGoogle Scholar
  16. Lowe TM, Chan PP. tRNAscan-SE On-line: integrating search and context for analysis of transfer RNA genes. Nucleic Acids Res. 2016;44:W54–7.View ArticlePubMedPubMed CentralGoogle Scholar
  17. Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, et al. CDD: a conserved domain database for the functional annotation of proteins. Nucleic Acids Res. 2011;39:225–9.View ArticleGoogle Scholar
  18. Finn RD, Attwood TK, Babbitt PC, Bateman A, Bork P, Bridge AJ, et al. InterPro in 2017-beyond protein family and domain annotations. Nucleic Acids Res. 2017;45:190–9.View ArticleGoogle Scholar
  19. van Heel AJ, de Jong A, Montalbán-López M, Kok J, Kuipers OP. BAGEL3: automated identification of genes encoding bacteriocins and (non-)bactericidal posttranslationally modified peptides. Nucleic Acids Res. 2013;41:448–53.View ArticleGoogle Scholar
  20. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S, Lund O, et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother. 2012;67:2640–4.View ArticlePubMedPubMed CentralGoogle Scholar
  21. Arndt D, Grant JR, Marcu A, Sajed T, Pon A, Liang Y, et al. PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res. 2016;44:W16–21.View ArticlePubMedPubMed CentralGoogle Scholar
  22. Grissa I, Vergnaud G, Pourcel C. CRISPRFinder: a web tool to identify clustered regularly interspace short palindromic repeats. Nucleic Acids Res. 2007;35:52–7.View ArticleGoogle Scholar
  23. Bland C, Ramsey TL, Sabree F, Lowe M, Brown K, Kyrpides NC, et al. CRISPR Recognition Tool (CRT): a tool for automatic detection of clustered regularly interspaced palindromic repeats. BMC Bioinform. 2007;8:209.View ArticleGoogle Scholar
  24. Stothard P, Wishart DS. Circular genome visualization and exploration using CGView. Bioinformatics. 2005;21:537–9.View ArticlePubMedGoogle Scholar
  25. Alikhan N-F, Petty NK, Ben Zakour NL, Beatson SA. BLAST Ring Image Generator (BRIG): simple prokaryote genome comparisons. BMC Genom. 2011;12:402–10.View ArticleGoogle Scholar
  26. Aleksandrzak-Piekarczyk T, Koryszewska-Baginska A, Bardowski J. Genome sequence of the probiotic strain Lactobacillus rhamnosus (formerly Lactobacillus casei) LOCK900. Genome Announc. 2013;1:e00640–713.View ArticlePubMedPubMed CentralGoogle Scholar
  27. Morita H, Toh H, Oshima K, Murakami M, Taylor TD, Igimi S, et al. Complete genome sequence of the probiotic Lactobacillus rhamnosus ATCC 53103. J Bacteriol. 2009;191:7630–1.View ArticlePubMedPubMed CentralGoogle Scholar
  28. Toh H, Oshima K, Nakano A, Takahata M, Murakami M, Takaki T, et al. Genomic adaptation of the Lactobacillus casei group. PLoS ONE. 2013;8:e75073.View ArticlePubMedPubMed CentralGoogle Scholar
  29. Douillard FP, Ribbera A, Kant R, Pietilä TE, Järvinen HM, Messing M, et al. Comparative genomic and functional analysis of 100 Lactobacillus rhamnosus strains and their comparison with strain GG. PLoS Genet. 2013;9:e1003683.View ArticlePubMedPubMed CentralGoogle Scholar
  30. Marcotte H, Krogh Andersen K, Lin Y, Zuo F, Zeng Z, Larsson PG, et al. Characterization and complete genome sequences of L. rhamnosus DSM 14870 and L. gasseri DSM 14869 contained in the EcoVag®probiotic vaginal capsules. Microbiol Res. 2017;205:88–98.View ArticlePubMedGoogle Scholar
  31. Nadkarni MA, Chen Z, Wilkins MR, Hunter N. Comparative genome analysis of Lactobacillus rhamnosus clinical isolates from initial stages of dental pulp infection: Identification of a new exopolysaccharide cluster. PLoS ONE. 2014;9:e90643.View ArticlePubMedPubMed CentralGoogle Scholar
  32. Nissilä E, Douillard FP, Ritari J, Paulin L, Järvinen HM, Rasinkangas P, et al. Genotypic and phenotypic diversity of Lactobacillus rhamnosus clinical isolates, their comparison with strain GG and their recognition by complement system. PLoS ONE. 2017;12:e0176739.View ArticlePubMedPubMed CentralGoogle Scholar
  33. Gueimonde M, Sánchez B, Reyes-Gavilán C, Margolles A. Antibiotic resistance in probiotic bacteria. Front Microbiol. 2013;4:202.View ArticlePubMedPubMed CentralGoogle Scholar
  34. Ceapa C, Davids M, Ritari J, Lambert J, Wels M, Douillard FP, et al. The variable regions of Lactobacillus rhamnosus genomes reveal the dynamic evolution of metabolic and host-adaptation repertoires. Genome Biol Evol. 2016;8:1889–905.View ArticlePubMedPubMed CentralGoogle Scholar
  35. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007;315:1709–12.View ArticlePubMedGoogle Scholar
  36. Durmaz E, Miller MJ, Azcarate-Peril MA, Toon SP, Klaenhammer TR. Genome sequence and characteristics of Lrm1, a prophage from industrial Lactobacillus rhamnosus strain M1. Appl Environ Microbiol. 2008;74:4601–9.View ArticlePubMedPubMed CentralGoogle Scholar
  37. Tuohimaa A, Riipinen KA, Brandt K, Alatossava T. The genome of the virulent phage Lc-Nu of probiotic Lactobacillus rhamnosus, and comparative genomics with Lactobacillus casei phages. Arch Virol. 2006;151:947–65.View ArticlePubMedGoogle Scholar
  38. Jarocki P, Podleśny M, Pawelec J, Malinowska A, Kowalczyk S, Targoński Z. Spontaneous release of bacteriophage particles by Lactobacillus rhamnosus Pen. J Microbiol Biotechnol. 2013;23:357–63.View ArticlePubMedGoogle Scholar
  39. Wang X, Kim Y, Ma Q, Hong SH, Pokusaeva K, Sturino JM, et al. Cryptic prophages help bacteria cope with adverse environments. Nat Commun. 2010;1:147.View ArticlePubMedPubMed CentralGoogle Scholar
  40. Nanda AM, Thormann K, Frunzke J. Impact of spontaneous prophage induction on the fitness of bacterial populations and host-microbe interactions. J Bacteriol. 2015;197:410–9.View ArticlePubMedPubMed CentralGoogle Scholar
  41. Sturino J. Chimeric bacteriophages, chimeric phage-like particles, and chimeric phage ghost particles, methods for their production and use. 2007. https://www.google.com.pg/patents/US20070248573. Accessed 20 Dec 2017.

Copyright

© The Author(s) 2018

Advertisement