Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 2181 2022-11-29 12:20:31 |
2 format correct + 3 word(s) 2184 2022-11-30 09:48:40 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Ji, Y.;  Zhang, P.;  Zhou, S.;  Gao, P.;  Wang, B.;  Jiang, J. The Parasitic or Symbiotic Lifestyle of CPR Bacteria. Encyclopedia. Available online: (accessed on 19 June 2024).
Ji Y,  Zhang P,  Zhou S,  Gao P,  Wang B,  Jiang J. The Parasitic or Symbiotic Lifestyle of CPR Bacteria. Encyclopedia. Available at: Accessed June 19, 2024.
Ji, Yanhan, Ping Zhang, Sihan Zhou, Ping Gao, Baozhan Wang, Jiandong Jiang. "The Parasitic or Symbiotic Lifestyle of CPR Bacteria" Encyclopedia, (accessed June 19, 2024).
Ji, Y.,  Zhang, P.,  Zhou, S.,  Gao, P.,  Wang, B., & Jiang, J. (2022, November 29). The Parasitic or Symbiotic Lifestyle of CPR Bacteria. In Encyclopedia.
Ji, Yanhan, et al. "The Parasitic or Symbiotic Lifestyle of CPR Bacteria." Encyclopedia. Web. 29 November, 2022.
The Parasitic or Symbiotic Lifestyle of CPR Bacteria

Candidate Phyla Radiation (CPR) bacteria is a bacterial division composed mainly of candidate phyla bacteria with ultra-small cell sizes, streamlined genomes, and limited metabolic capacity, which are generally considered to survive in a parasitic or symbiotic manner.

candidate phyla radiation (CPR) patescibacteria metabolic characteristic

1. Unique Genomic and Morphological Characteristics

Small cell sizes and streamlined genomes are the most common features of Candidate Phyla Radiation (CPR) bacteria. Combining metagenomic analysis with size fraction (1.2–0.2–0.1 μm), CPR bacteria were found to be enriched on small pore size filters (0.1/0.2 μm) [1][2]. Cryogenic transmission electron microscopy results also demonstrated that CPR bacteria have an ultra-small cell size, and some CPR bacteria can pass through a 0.2 μm filter [3]. In 2015, He et al. isolated and co-cultured a CPR strain TM7x, with its bacterial host (Actinomyces spp. XH001) from the human oral cavity. The CPR strain TM7x was spherical with a diameter of 200–300 nm, as judged by microscopic observation [4]. In 2021, Batinovic et al. isolated another CPR strain JR1 from wastewater, which could violently lyse foaming strains (Gordonia amarae) [5]. The cell size of strain JR1 observed by electron microscopy was between 0.2 μm and 0.5 μm. Through electron microscope observation, the morphology of CPR bacteria is determined to be mainly rod or spherical.
The genome sizes of all CPR bacteria obtained so far are less than 1.5 Mbp. Compared with normal bacteria, archaea and obligate insect symbionts, the genome size of CPR bacteria is closer to that of obligate insect symbionts, and significantly smaller than that of most normal bacteria [6]. Castelle et al. analyzed and compared approximately 1000 CPR genomes, and found that most of the CPR genomes had genes related to homologous recombination, base excision repair and mismatch repair, suggesting that the streamlined genome of CPR bacteria is a trait inherited from their ancestors, rather than a reduction in genome evolution [6]. After comparing three genomes of CPR bacteria of Absconditabacteria (SR1), Moreira et al. found that there were only 390 conserved genes in this type of CPR bacteria [7]. Based on the comparative study of CPR genomes among three different taxa (SR1, GN02, PER), it was found that these three CPR phyla may have recently lost 30–50% of genes from their common ancestor, and it was speculated that the genome content of these CPR bacteria had an active dynamic evolution [7]. Whether the streamlined genome of CPR is just an ancestral trait or the result of reductive evolution still requires further investigation.
Interestingly, CPR bacteria often have self-splicing introns and proteins encoded within their rRNA genes. In total, 1543 CPR bacterial 16S rRNA genes (>800 bp) assembled from the groundwater near the town of Rifle in USA were clustered into 713 sequences at 97% identity. It was found that 31% of 16S rRNA genes encoded insertion sequences larger than 10 bp, and most of the sequences over 500 bp encoded a catalytic RNA intron or an open reading frame (ORF), suggesting that CPR bacteria were self-splicing, which was supported by metatranscriptomic analysis [1]. Based on the analysis of about 1000 CPR genomes, it was found that the phenomenon of an insertion sequence also existed in 23S rRNA and tRNAs genes [6]. A study on primer fidelity in SSU (small subunit ribosome) rRNA gene sequences suggested that 70% of the SSU rRNA gene sequences of CPR bacteria would be missed when using bacterial universal primer 515F-806R [8]. Furthermore, the ribosomal protein composition of CPR bacteria is also different from that of other bacteria. CPR bacteria usually lack some ribosomal proteins that are ubiquitous in other bacteria, such as ribosomal proteins uL1, bL9, and uL30, and such features are similar to some parasitic microorganisms [1]. Further, the ribosomal proteins bL28, uL29, bL32, and bL33 are also lost in some specific lineages of CPR bacteria [9]. In addition, several regions in ribosomal proteins as well as in the 16S, 23S, 5S rRNAs of CPR bacteria were lacking, and these missing regions were predicated to be located near the surface of the ribosome, implying that CPR bacteria might possess smaller ribosomes with more simplified surface structures than other non-CPR bacteria [9].
Together, the virus-sized cell sizes, self-splicing introns and proteins encoded within rRNA genes, and mismatch between the universal bacterial 16S rRNA gene primers and SSU rRNA gene sequences of CPR make the detection of CPR bacteria in environments especially difficult.

2. Potential Metabolism

The streamlined genomes limit the metabolic capacity of CPR bacteria. Current studies have shown that most CPR bacteria lack a complete respiratory chain, including the NADH dehydrogenase and oxidative phosphorylation complex, and the tricarboxylic acid (TCA) cycle, suggesting that CPR bacteria may be anaerobic [2]. CPR bacteria have an incomplete glycolytic pathway, and lack 6-phosphofructokinase and glucokinase. CPR bacteria usually contain genes related to the Pentose Phosphate Pathway (PPP). Therefore, it is speculated that CPR bacteria can convert fructose-6-phosphate to glyceraldehyde-3-phosphate through the non-oxidative PPP pathway [6]. Usually, pyruvate or acetyl-CoA is the end-product of central carbon metabolism in CPR bacteria. They generally first convert pyruvate to acetyl-CoA, and then further use it to produce short-chain fatty acids. For example, many CPR bacteria such as parcubacteria (OD1), dojkabacteria (WS6) and microgenomates (OP11) are predicted to utilize the ADP-acetyl-CoA synthase (ADP-Acs) commonly found in archaea to generate acetate [10]. Some peregrinibacteria (PER) can also produce acetate via acetate kinase (Ack) and phosphotransacetylase (Pta), which are common in bacteria. In addition to acetate, many CPR bacteria can produce products such as lactic acid, formic acid, or ethanol through fermentation [6].
The lack of complete amino acid, nucleotide and lipid synthesis pathways is a common feature of CPR bacteria, but the biosynthetic capacities of different lineages of CPR bacteria vary greatly [6]. Certain genomes from peregrinibacteria (PER) have relatively more core biological metabolic capabilities, and all seem to have the ability to synthesize nucleotides, certain amino acids, and cofactors, but not fatty acids [11]. Compared to peregrinibacteria (PER), katanobacteria (SM2F11), KAZAN and WS6 have the least biosynthetic and metabolic capabilities, and they lack the ability to synthesize nucleotides, amino acids, lipids, peptidoglycan, and various auxiliaries [6]. The great metabolic differences among CPR bacteria suggest that although all CPR bacteria are predicted to require parasitism or symbiosis to survive, different lineages of CPR may differ in degrees of dependence on their host.

3. Isolation and Culture of CPR

With the wide application of high-throughput sequencing technology, an increasing number of CPR bacteria have been detected in various environments, but most studies are mainly based on the metagenome-assembled genomes (MAGs), lacking the isolates of a pure culture of CPR [1][12][13]. Among the more than 70 phylum-level lineages of CPR bacteria, only a few lineages have been isolated in binary cultures that could be stably passaged, such as saccharibacteria [4][14], which are summarized in Table 1. Furthermore, although most CPR bacteria are inferred to be symbionts, there is still a lack of reliable and standardized methods to obtain pure binary cultures of CPR bacteria and their hosts.
Table 1. Summary of parasitic/symbiotic interrelationships between CPR bacteria and their hosts.

3.1. Saccharibacteria (TM7)

The first pure strain of CPR bacteria, TM7x, was isolated from a human oral cavity [4]. By serial sub-cultivation with the addition of streptomycin (given the resistance of TM7x to streptomycin), an enrichment-containing strain TM7x and multispecies was obtained, then the pure binary co-culture of strain TM7x with its host, Actinomyces odontolyticus strain XH001, was isolated using SHI medium (a medium for culturing saliva-derived oral microbial) agar plate. The growth of TM7x was obligately dependent on its host strain XH001, and neither the addition of spent co-culture medium nor heat-killed XH001 could lead to the independent growth of TM7x [4]. Further studies reveal that strains TM7x/XH001 could co-exist well under nutrient-replete condition, but the infection of strain XH100 with strain TM7x would lead to a severely disrupted cell membrane in the host and a consequently decreased viability of strain XH001 under extended starvation conditions, suggesting a parasitic rather mutualistic or commensal relationship between strains TM7x and XH001 [4].
Strain TM7x elicited differential responses to its different hosts. For some hosts, the rapid growth of strain TM7x at the initial stage of co-cultivation would lead to a large number of deaths of its hosts [17]. After several passages, hosts would rapidly evolve to adapt to strain TM7x and form a long-term stable binary culture. Due to the genetic changes in the host during several passages, the growth collapse phenomenon of the host only occurred at the early stage of infection [17]. However, not all related Actinomyces strains showed such high susceptibility to strain TM7x, and some exhibited no growth–crash phase when infected by strain TM7x before establishing a stable binary co-culture [18]. The further comparative genomic analysis revealed only very small genetic differences between hosts with varying susceptibility to strain TM7x [18]. Furthermore, the acquisition of the arginine deiminase system (ADS) could allow strain TM7x to maintain higher activity and infectivity when disassociated from its host, and protected strain TM7x and its host from acid stress in oral cavity [19]. It was intriguing that strain TM7x containing ADS only preferred the hosts lacking the ADS system, and not those carrying ADS, suggesting the importance of ADS to the partner selection for episymbiosis within the mammalian microbiome [19].
Based on 16S rRNA gene sequencing, it was found that the abundance of TM7 in the mouth of patients with periodontitis was higher than that of healthy people, indicating that TM7 might be a pathogen. However, through the mouse oral infection model, it was found that strain TM7x can provide protection to the mammalian host by reducing the pathogenicity to the host, indicating that strains with increased abundance in disease were not necessarily harmful [20]. In addition, is TM7 also associated with the phenomenon of preying on hosts, lysing hosts like a virus. CPR strain (TM7-JR1) was isolated from a wastewater by an accidental attempt [5]. Gordonia amarae, one of the most common foaming bacteria, has multiple antiviral mechanisms within its genome. In order to isolate phages that could lyse G. amarae, the in situ wastewater was filtered through a 0.45 μm filter membrane, and then the filtrate was directly applied to a colony of G. amarae, but one CPR strain (TM7-JR1) that could strongly lyse G. amarae was accidentally isolated. The lifestyle of strain TM7-JR1 that lyses its host like a virus provides a new perspective on the relationships between CPR and its host.

3.2. Absconditabacteria (SR1)

The first in-depth characterization of Absconditabacteria (SR1) was based on the environmental observation and genome-inferred biology of a strain named “Candidatus Vampirococcus lugosii[7]. Many photosynthetic bacteria were observed with one or several enigmatic small and dark nonflagellated cells attached to their surface in an enrichment cultured from microbial mats collected from a permanent hypersaline lake in Western Europe; in some cases, the epibionts were associated to empty ghost cells where only the photosynthesis-derived sulfur granules persisted [7]. These epibionts were called “Candidatus Vampirococcus lugosii” because the phenotypic characteristics were in agreement with the genus Vampirococcus observed over forty years ago, and might belong to the same genus. 16S rRNA gene sequencing and analysis of both the epibiont and the host for ten infected cells collected by the micromanipulator found that the two bacteria were halochromatium-like γ-proteobacterium and SR1. Combined with micromanipulation and whole-genome amplification sequencing, two MAGs were obtained, belonging to the gamma-proteobacteria photosynthetic bacteria and the candidate phylum SR1 of CPR bacteria, respectively, in which the genome of strain “Candidatus Vampirococcus lugosii” was relatively complete, while the host genome was partially assembled (15%), indicating that the epibiont might consume the host DNA [7]. Besides this, the genome sequence of SR1 obtained in their study coded a very simplified metabolism and a complex cell surface, implying that the attachment of SR1 to its host by type IV pili is needed to obtain all cell components it needs [7]. The first stably cultivated species of SR1, “Ca. Absconditicoccus praedator” M39-6, was isolated from the hypersaline alkaline Lake Hotontyn Nur, Mongolia. M39-6 appeared to share a similar biology with the other genus “Candidatus Vampirococcus lugosii”: an obligate parasitic lifestyle, feeding on photosynthetic anoxygenic γ-proteobacteria, and the complete consumption of the host cytoplasm, suggesting that predation on hosts might be a common feature of microorganisms in this lineage [14].
Cross-domain parasitism between CPR bacteria and their hosts has also been observed. A strain of CPR bacteria (yanofskybacteria), specifically parasitizing methanogenic archaea Methanothrix, was isolated from wastewater treatment sludge samples [15]. The cellular deformation and reduced activity of Methanothrix filaments (multicellular) attached to Ca. yanofskybacteria implied that the interaction was parasitic [15]. Transmission electron microscopy and FISH with specific probes showed that protists might be important hosts for some CPR bacteria [16]. The host range of CPR bacteria includes more than just bacteria, but the study of the relationship between CPR bacteria and their hosts is still limited by the lack of isolates.


  1. Brown, C.T.; Hug, L.A.; Thomas, B.C.; Sharon, I.; Castelle, C.J.; Singh, A.; Wilkins, M.J.; Wrighton, K.C.; Williams, K.H.; Banfield, J.F. Unusual biology across a group comprising more than 15% of domain Bacteria. Nature 2015, 523, 208–211.
  2. Wrighton, K.C.; Thomas, B.C.; Sharon, I.; Miller, C.S.; Castelle, C.J.; Verberkmoes, N.C.; Wilkins, M.J.; Hettich, R.L.; Lipton, M.S.; Williams, K.H.; et al. Fermentation, hydrogen, and sulfur metabolism in multiple uncultivated bacterial phyla. Science 2012, 337, 1661–1665.
  3. Luef, B.; Frischkorn, K.R.; Wrighton, K.C.; Holman, H.N.; Birarda, G.; Thomas, B.C.; Singh, A.; Williams, K.H.; Siegerist, C.E.; Tringe, S.G.; et al. Diverse uncultivated ultra-small bacterial cells in groundwater. Nat. Commun. 2015, 6, 6372.
  4. He, X.; Mclean, J.S.; Edlund, A.; Yooseph, S.; Hall, A.P.; Liu, S.; Dorrestein, P.C.; Esquenazi, E.; Hunter, R.C.; Cheng, G.; et al. Cultivation of a human-associated TM7 phylotype reveals a reduced genome and epibiotic parasitic lifestyle. Proc. Natl. Acad. Sci. USA 2015, 112, 244–249.
  5. Batinovic, S.; Rose, J.J.A.; Ratcliffe, J.; Seviour, R.J.; Petrovski, S. Cocultivation of an ultrasmall environmental parasitic bacterium with lytic ability against bacteria associated with wastewater foams. Nat. Microbiol. 2021, 6, 703–711.
  6. Castelle, C.J.; Brown, C.T.; Anantharaman, K.; Probst, A.J.; Huang, R.H.; Banfield, J.F. Biosynthetic capacity, metabolic variety and unusual biology in the CPR and DPANN radiations. Nat. Rev. Microbiol. 2018, 16, 629–645.
  7. Moreira, D.; Zivanovic, Y.; López-Archilla, A.I.; Iniesto, M.; López-García, P. Reductive evolution and unique predatory mode in the CPR bacterium Vampirococcus lugosii. Nat. Commun. 2021, 12, 2454.
  8. Eloe-Fadrosh, E.A.; Ivanova, N.N.; Woyke, T.; Kyrpides, N.C. Metagenomics uncovers gaps in amplicon-based detection of microbial diversity. Nat. Microbiol. 2016, 1, 15032.
  9. Tsurumaki, M.; Saito, M.; Tomita, M.; Kanai, A. Features of smaller ribosomes in candidate phyla radiation (CPR) bacteria revealed with a molecular evolutionary analysis. RNA 2022, 28, 1041–1057.
  10. Kowarsky, M.; Camunas-Soler, J.; Kertesz, M.; De Vlaminck, I.; Koh, W.; Pan, W.; Martin, L.; Neff, N.F.; Okamoto, J.; Wong, R.J.; et al. Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA. Proc. Natl. Acad. Sci. USA 2017, 114, 9623–9628.
  11. Anantharaman, K.; Brown, C.T.; Burstein, D.; Castelle, C.J.; Probst, A.J.; Thomas, B.C.; Williams, K.H.; Banfield, J.F. Analysis of five complete genome sequences for members of the class Peribacteria in the recently recognized Peregrinibacteria bacterial phylum. PeerJ 2016, 4, e1607.
  12. Chiriac, M.C.; Bulzu, P.A.; Andrei, A.S.; Okazaki, Y.; Nakano, S.I.; Haber, M.; Kavagutti, V.S.; Layoun, P.; Ghai, R.; Salcher, M.M. Ecogenomics sheds light on diverse lifestyle strategies in freshwater CPR. Microbiome 2022, 10, 84.
  13. He, C.; Keren, R.; Whittaker, M.L.; Farag, I.F.; Doudna, J.A.; Cate, J.; Banfield, J.F. Genome-resolved metagenomics reveals site-specific diversity of episymbiotic CPR bacteria and DPANN archaea in groundwater ecosystems. Nat. Microbiol. 2021, 6, 354–365.
  14. Yakimov, M.M.; Merkel, A.Y.; Gaisin, V.A.; Pilhofer, M.; Messina, E.; Hallsworth, J.E.; Klyukina, A.A.; Tikhonova, E.N.; Gorlenko, V.M. Cultivation of a vampire: ‘Candidatus Absconditicoccus praedator’. Environ. Microbiol. 2022, 24, 30–49.
  15. Kuroda, K.; Yamamoto, K.; Nakai, R.; Hirakata, Y.; Kubota, K.; Nobu, M.K.; Narihiro, T. Symbiosis between Candidatus Patescibacteria and Archaea Discovered in Wastewater-Treating Bioreactors. mBio 2022, 13, e01711-22.
  16. Gong, J.; Qing, Y.; Guo, X.; Warren, A. “Candidatus Sonnebornia yantaiensis”, a member of candidate division OD1, as intracellular bacteria of the ciliated protist Paramecium bursaria (Ciliophora, Oligohymenophorea). Syst. Appl. Microbiol. 2014, 37, 35–41.
  17. Bor, B.; Mclean, J.S.; Foster, K.R.; Cen, L.; To, T.T.; Serrato-Guillen, A.; Dewhirst, F.E.; Shi, W.; He, X. Rapid evolution of decreased host susceptibility drives a stable relationship between ultrasmall parasite TM7x and its bacterial host. Proc. Natl. Acad. Sci. USA 2018, 115, 12277–12282.
  18. Utter, D.R.; He, X.; Cavanaugh, C.M.; Mclean, J.S.; Bor, B. The saccharibacterium TM7x elicits differential responses across its host range. ISME J. 2020, 14, 3054–3067.
  19. Tian, J.; Utter, D.R.; Cen, L.; Dong, P.; Shi, W.; Bor, B.; Qin, M.; Mclean, J.S.; He, X. Acquisition of the arginine deiminase system benefits epiparasitic Saccharibacteria and their host bacteria in a mammalian niche environment. Proc. Natl. Acad. Sci. USA 2022, 119, e2114909119.
  20. Chipashvili, O.; Utter, D.R.; Bedree, J.K.; Ma, Y.; Schulte, F.; Mascarin, G.; Alayyoubi, Y.; Chouhan, D.; Hardt, M.; Bidlack, F.; et al. Episymbiotic Saccharibacteria suppresses gingival inflammation and bone loss in mice through host bacterial modulation. Cell Host Microbe 2021, 29, 1649–1662.
Subjects: Microbiology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , , , ,
View Times: 453
Revisions: 2 times (View History)
Update Date: 30 Nov 2022
Video Production Service