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Antibiotics from Haloarchaea: What Can We Learn from Comparative Genomics?

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Abstract

The knowledge of antibiotics produced by Archaea (archaeocins) is still limited. So far, only two types of archaeocins are known: (i) sulfolobicins, produced by the extremely thermophilic Sulfolobus spp. and (ii) haloarcheocins, produced by halophilic archaea. Haloarcheocins were first discovered in the 1980s, but most of their characterisation was solely based on supernatant-based assays. Only a few were successfully purified and sequenced, and even fewer have a proposed biosynthetic model. Furthermore, their mode of action, ecological role and biotechnological potential are still to be explored. Haloarcheocin C8 (HalC8) is the best well-characterised haloarcheocin. We applied an approach of comparative genomics in order to go a step further in the knowledge of their biosynthetic clusters as well as the clusters encoding HalC8-like peptides. These peptides can be classified, at least, into 4 different clades, and there is low gene conservation between them. However, the putative function of some proteins is conserved. These include uncharacterized major facilitator superfamily proteins, transmembrane peptides, DNA-binding transcriptional regulators and proteins with extracellular domains. Our analysis reinforces the association of these proteins with HalC8/HalC8-like biosynthesis. Their functionality is unknown, and, in an era where it is known that haloarchaea are not confined to high salt habitats, the advance in the knowledge of their specialised metabolites will be imperative.

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References

  • Asgarani E, Funamizu H, Saito T, Terato H, Ohyama Y (1999) Mechanisms of DNA protection in Halobacterium salinarium, an extremely halophilic bacterium. Microbiol Res 154:185–190

    Article  CAS  Google Scholar 

  • Atanasova NS, Pietilä MK, Oksanen HM (2013) Diverse antimicrobial interactions of halophilic archaea and bacteria extend over geographical distances and cross the domain barrier. Microbiologyopen 2:811–825

    PubMed  PubMed Central  Google Scholar 

  • Besse A, Peduzzi J, Rebuffat S, Carré-Mlouka A (2015) Antimicrobial peptides and proteins in the face of extremes: lessons from archaeocins. Biochimie 118:344–355

    Article  CAS  Google Scholar 

  • Besse A, Vandervennet M, Goulard C, Peduzzi J, Isaac S, Rebuffat S, Carré-Mlouka A (2017) Halocin C8: an antimicrobial peptide distributed among four halophilic archaeal genera: Natrinema, Haloterrigena, Haloferax, and Halobacterium. Extremophiles 21:623–638

    Article  CAS  Google Scholar 

  • Carver T, Harris SR, Berriman M, Parkhill J, Mcquillan JA (2012) Artemis: an integrated platform for visualization and analysis of high-throughput sequence-based experimental data. Bioinformatics 28:464–469

  • Chen S, Sun S, Korfanty GA, Liu J, Xiang H (2019) A halocin promotes DNA uptake in Haloferax mediterranei. Front Microbiol 10:1960

  • Cheung J, Danna KJ, O’Connor EM, Price LB, Shand RF (1997) Isolation, sequence, and expression of the gene encoding halocin H4, a bacteriocin from the halophilic archaeon Haloferax mediterranei R4. J Bacteriol 179:548–551

    Article  CAS  Google Scholar 

  • Fendrihan S, Legat A, Pfaffenhuemer M, Gruber C, Weidler G, Gerbl F, Stan-Lotter H (2006) Extremely halophilic archaea and the issue of long-term microbial survival. Rev Environ Sci Biotechnol 5:203–218

    Article  CAS  Google Scholar 

  • Ghanmi F, Carré-Mlouka A, Zarai Z, Mejdoub H, Peduzzi J, Maalej S, Rebuffat S (2019) The extremely halophilic archaeon Halobacterium salinarum ETD5 from the solar saltern of Sfax (Tunisia) produces multiple halocins. Res Microbiol S0923-2508:30097-X

  • Giani M, Garbayo I, Vílchez C, Martínez-Espinosa RM (2019) Haloarchaeal carotenoids: healthy novel compounds from extreme environments. Mar Drugs 17:524

  • Jiang L, Wen L (2015) Photonic sensitive switchable materials. In Switchable and Responsive Surfaces and Materials for Biomedical Applications. Materials Science, pp 93–118

  • Karr EA (2014) Transcription regulation in the third domain. Adv Appl Microbiol 89:101–33

  • Kis-Papo T, Oren A (2000) Halocins: are they involved in the competition between halobacteria in saltern ponds? Extremophiles 4:35–41

    Article  CAS  Google Scholar 

  • Krogh A, Larsson B, von Heijne G, Sonnhammer ELL (2001) Predicting transmembrane protein topology with a hidden markov model: application to complete genomes. J Mol Biol 305:567–580

    Article  CAS  Google Scholar 

  • Kumar V, Tiwari SK (2017) Activity-guided separation and characterization of new halocin HA3 from fermented broth of Haloferax larsenii HA3. Extremophiles 21:609–621

    Article  CAS  Google Scholar 

  • Li Y, Xiang H, Liu J, Zhou M, Tan H (2003) Purification and biological characterization of halocin C8, a novel peptide antibiotic from Halobacterium strain AS7092. Extremophiles 7:401–407

    Article  CAS  Google Scholar 

  • Makarova KS, Wolf YI, Karamycheva S, Zhang D, Aravind L (2019) Antimicrobial peptides, polymorphic toxins, and self-nonself recognition systems in Archaea: an untapped armory for intermicrobial conflicts. mBio 10:e00715–19

  • Mazguene S, Rossi M, Gogliettino M, Palmieri G, Cocca E, Mirino S, Imadalou-Idres N, Benallaoua S (2018) Isolation and characterization from solar salterns of North Algeria of a haloarchaeon producing a new halocin. Extremophiles 22:259–270

    Article  CAS  Google Scholar 

  • Mei S-S, Li Y, Lu Q-H, Xiang H (2006) Cloning and analysis of genes in the halocin C8 gene cluster. Wei Sheng Wu Xue Bao 46:318–322

    CAS  PubMed  Google Scholar 

  • Mei S, Sun C, Liu X, Lu Q, Cai L, Li Y, Xiang H (2008) The helix-loop-helix motif at the N terminus of HalI is essential for its immunity function against halocin C8. J Bacteriol 190:6501–6508

    Article  CAS  Google Scholar 

  • Meseguer I, Rodriguez-Valera F (1985) Production and purification of halocin H4. FEMS Microbiol Lett 28:177–182

    Article  CAS  Google Scholar 

  • Meseguer I, Torreblanca M, Konishi T (1995) Specific inhibition of the halobacterial Na+/H+ antiporter by halocin H6. J Biol Chem 270:6450–6455

    Article  CAS  Google Scholar 

  • Mitchell AL, Attwood TK, Babbitt PC, Blum M, Bork P, Bridge A et al (2019) InterPro in 2019: improving coverage , classification and access to protein sequence annotations. Nucleic Acids Res 47:351–360

  • Naor A, Yair Y, Gophna U (2013) A halocin-H4 mutant Haloferax mediterranei strain retains the ability to inhibit growth of other halophilic archaea. Extremophiles 17:973–979

    Article  CAS  Google Scholar 

  • Nielsen H, Engelbrecht J, Brunak S, von Heijne G (1997) Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng 10:1–6

    Article  CAS  Google Scholar 

  • Nkamga VD, Henrissat B, Drancourt M (2017) Archaea: essential inhabitants of the human digestive microbiota. Hum Microbiome J 3:1–8

    Article  Google Scholar 

  • O’Connor EM, Shand RF (2002) Halocins and sulfolobicins: the emerging story of archaeal protein and peptide antibiotics. J Ind Microbiol Biotechnol 28:23–31

    Article  Google Scholar 

  • Piotto S, Di Biasi L, Sessa L, Concilio S (2018) Transmembrane peptides as sensors of the membrane physical state. Front Phys 6:1–13

  • Rodriguez-Valera F, Juez G, Kushner DJ (1982) Halocins: salt-dependent bacteriocins produced by extremely halophilic rods. Can J Microbiol 28:151–154

  • Saier MH, Reddy VS, Tsu BV, Ahmed MS, Li C, Moreno-hagelsieb G (2016) The transporter classification database (TCDB): recent advances. Nucleic Acids Res 44:D372–D379

  • Seck EH, Senghor B, Merhej V, Bachar D, Cadoret F, Robert C, Azhar EI, Yasir M, Bibi F, Jiman-Fatani AA, Konate DS, Musso D, Doumbo O, Sokhna C, Levasseur A, Lagier JC, Khelaifia S, Million M, Raoult D (2019) Salt in stools is associated with obesity, gut halophilic microbiota and Akkermansia muciniphila depletion in humans. Int J Obes 43:862–871

    Article  CAS  Google Scholar 

  • Shand RF, Leyva KJ (2007) Peptide and protein antibiotics from the domain Archaea: halocins and sulfolobicins. In Bacteriocins: ecology and evolution. Ed by Riley MA, Chavan MA. Springer, pp 93–109

  • Solovyev V, Salamov A (2011) Automatic annotation of microbial genomes and metagenomic sequences. In: Metagenomics and its applications in agriculture, biomedicine and environmental studies (Ed. R.W. Li). Nova Science Publishers, pp 61–78

  • Sullivan MJ, Petty NK, Beatson SA (2011) Easyfig: a genome comparison visualizer. Bioinformatics 27:1009–1010

    Article  CAS  Google Scholar 

  • Sun C, Li Y, Mei S, Lu Q, Zhou L, Xiang H (2005) A single gene directs both production and immunity of halocin C8 in a haloarchaeal strain AS7092. Mol Microbiol 57:537–549

    Article  CAS  Google Scholar 

  • Torregrosa-Crespo J, Pire Galiana C, Martínez-Espinosa RM (2017) Biocompounds from Haloarchaea and their uses in biotechnology. In Archaea - New Biocatalysts, Novel Pharmaceuticals and Various Biotechnological Applications (Ed by Sghaier H, Najjari A, Ghedira K). IntechOpen, pp 63–82 

  • Torregrosa-Crespo J, Montero Z, Fuentes JL, García-Galbis MR, Garbayo I, Vílchez C, Martínez-Espinosa RM (2018) Exploring the valuable carotenoids for the large-scale production by marine microorganisms. Mar Drugs 16:203

  • Ulrich LE, Koonin EV, Zhulin IB (2005) One-component systems dominate signal transduction in prokaryotes. Trends Microbiol 13:52–56

    Article  CAS  Google Scholar 

  • Woese CR, Fox GE (1977) Phylogenetic structure of the prokaryotic domain: the primary kingdoms. Proc Natl Acad Sci U S A 74:5088–5090

  • Yan, N. (2015) Structural biology of the major facilitator superfamily transporters. Annual Review of Biophysics 44:257–285

  • Zalazar L, Pagola P, Miró MV, Churio MS, Cerletti M, Martínez C et al (2019) Bacterioruberin extracts from a genetically modified hyperpigmented Haloferax volcanii strain: antioxidant activity and bioactive properties on sperm cells. J Appl Microbiol 126:796–810

    Article  CAS  Google Scholar 

Download references

Funding

Tânia Caetano is funded by national funds (OE), through FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19 (CEECIND/01463/2017). Thanks are due for the financial support to CESAM (UID/AMB/50017/2019), to FCT/MEC through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020.

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  1. Department of Biology and CESAM, University of Aveiro, Aveiro, Portugal

    Inês de Castro, Sónia Mendo & Tânia Caetano

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  1. Inês de Castro
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  2. Sónia Mendo
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  3. Tânia Caetano
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Correspondence to Tânia Caetano.

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de Castro, I., Mendo, S. & Caetano, T. Antibiotics from Haloarchaea: What Can We Learn from Comparative Genomics?. Mar Biotechnol 22, 308–316 (2020). https://doi.org/10.1007/s10126-020-09952-9

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