Exploring the potential positive impact of phage-bacterium interactions on membrane fouling mitigation

Bei Zang , Hang Zhou , Huakai Nan , Yu Li , Qian Li , Daisuke Sano , Rong Chen

Front. Environ. Sci. Eng. ›› 2025, Vol. 19 ›› Issue (10) : 139

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Front. Environ. Sci. Eng. ›› 2025, Vol. 19 ›› Issue (10) : 139 DOI: 10.1007/s11783-025-2059-7
RESEARCH ARTICLE

Exploring the potential positive impact of phage-bacterium interactions on membrane fouling mitigation

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Abstract

The stable operation of membrane bioreactors (MBRs) strongly depends on the extent of membrane fouling. Phages are gaining recognition as ideal and sustainable biological agents for mitigating membrane fouling, but the limited understanding of phage composition, function profiles, and their relationship with actual membrane fouling behavior greatly constrains engineering applications. This study demonstrated the critical role of phage-bacterium interactions in both the formation and mitigation of fouling in anaerobic membrane bioreactors (AnMBRs). Firstly, phages within the fouling layers exhibited greater diversity than those in sludge. Lytic phages in the fouling layers target ~42% of the top 100 most abundant species and biofilm-forming bacteria. In addition, adverse conditions caused by high transmembrane pressure (TMP) and the presence of harmful substances in sewage triggered prophage activation; notably, 19.1%–26.3% of contigs in the gel layer contained prophages, a 3.2- to 5.3-fold higher compared to sludge (3.6%–6.1%). These findings underscored the potential role of the phage lysis cycle in alleviating membrane fouling. Phage-encoded auxiliary metabolic genes (AMGs; 138 types in total) related to fouling formation, bacterial integrity, and stress tolerance were identified, potentially enhancing fouling stability. Conversely, phage-encoded AMGs associated with polysaccharide and protein degradation may promoted biofilm breakdown, and the combined lysis cycle further alleviate membrane fouling. Overall, this study revealed, for the first time, the potential role of phages in both the formation and mitigation of membrane fouling in AnMBRs, and provided theoretical support for phage therapy in controlling membrane fouling.

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Keywords

Phages / Anaerobic membrane bioreactor / Membrane fouling / Lytic / Auxiliary metabolic genes

Highlight

● Phage community diversity in the fouling layers exceeds that in the sludge.

● Lytic phages could mitigate membrane fouling by lying associated hosts.

● Phage-encoded AMGs probably mediate membrane fouling.

● The gel layer is an optimal target for activating prophages to mitigate fouling.

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Bei Zang, Hang Zhou, Huakai Nan, Yu Li, Qian Li, Daisuke Sano, Rong Chen. Exploring the potential positive impact of phage-bacterium interactions on membrane fouling mitigation. Front. Environ. Sci. Eng., 2025, 19(10): 139 DOI:10.1007/s11783-025-2059-7

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References

[1]

Al-Juboori R A, Yusaf T. (2012). Biofouling in RO system: mechanisms, monitoring and controlling. Desalination, 302: 1–23

[2]

Aslam A, Khan S J, Shahzad H M A. (2022). Anaerobic membrane bioreactors (AnMBRs) for municipal wastewater treatment-potential benefits, constraints, and future perspectives: an updated review. Science of the Total Environment, 802: 149612

[3]

Aydin S, Can K. (2020). Pyophage cocktail for the biocontrol of membrane fouling and its effect in aerobic microbial biofilm community during the treatment of antibiotics. Bioresource Technology, 318: 123965

[4]

Bolger A M, Lohse M, Usadel B. (2014). Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics, 30(15): 2114–2120

[5]

BushnellB (2014). BBMap: a Fast, Accurate, Splice-aware Aligner. Berkeley: Lawrence Berkeley National Laboratory

[6]

Chan B K, Abedon S T. (2015). Bacteriophages and their enzymes in biofilm control. Current Pharmaceutical Design, 21(1): 85–99

[7]

Chaumeil P A, Mussig A J, Hugenholtz P, Parks D H. (2020). GTDB-Tk: a toolkit to classify genomes with the Genome Taxonomy Database. Bioinformatics, 36(6): 1925–1927

[8]

Chevallereau A, Pons B J, van Houte S, Westra E R. (2022). Interactions between bacterial and phage communities in natural environments. Nature Reviews Microbiology, 20(1): 49–62

[9]

Cornuault J K, Moncaut E, Loux V, Mathieu A, Sokol H, Petit M A, de Paepe M. (2020). The enemy from within: a prophage of Roseburia intestinalis systematically turns lytic in the mouse gut, driving bacterial adaptation by CRISPR spacer acquisition. The ISME Journal, 14(3): 771–787

[10]

Deng L J, Guo W S, Ngo H H, Zhang H W, Wang J, Li J X, Xia S Q, Wu Y. (2016). Biofouling and control approaches in membrane bioreactors. Bioresource Technology, 221: 656–665

[11]

Ding A, Lin D C, Zhao Y X, Ngo H H, Guo W S, Bai L M, Luo X S, Li G B, Ren N Q, Liang H. (2019). Effect of metabolic uncoupler, 2,4-dinitrophenol (DNP) on sludge properties and fouling potential in ultrafiltration membrane process. Science of the Total Environment, 650: 1882–1888

[12]

Erez Z, Steinberger-Levy I, Shamir M, Doron S, Stokar-Avihail A, Peleg Y, Melamed S, Leavitt A, Savidor A, Albeck S. . (2017). Communication between viruses guides lysis–lysogeny decisions. Nature, 541(7638): 488–493

[13]

Fischetti V A. (2018). Development of phage lysins as novel therapeutics: a historical perspective. Viruses, 10(6): 310

[14]

Fu J W, Hou Z Y, Zhao H X, Li Q, Chen R, Li Y Y. (2024). Enhanced nitrogen removal from low strength anaerobic membrane bioreactor (AnMBR) permeate using complete nitrification and partial denitrification-anammox processes. Frontiers of Environmental Science & Engineering, 18(12): 155

[15]

Fu L M, Niu B F, Zhu Z W, Wu S T, Li W Z. (2012). CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics, 28(23): 3150–3152

[16]

Gliźniewicz M, Miłek D, Olszewska P, Czajkowski A, Serwin N, Cecerska-Heryć E, Dołęgowska B, Grygorcewicz B. (2024). Advances in bacteriophage-mediated strategies for combating polymicrobial biofilms. Frontiers in Microbiology, 14: 1320345

[17]

Gu X, Huang D, Chen J H, Li X, Zhou Y Q, Huang M H, Liu Y N, Yu P F. (2022). Bacterial inactivation and biofilm disruption through indigenous prophage activation using low-intensity cold atmospheric plasma. Environmental Science & Technology, 56(12): 8920–8931

[18]

Gutiérrez D, Ruas-Madiedo P, Martínez B, Rodríguez A, García P. (2014). Effective removal of staphylococcal biofilms by the endolysin LysH5. PLoS One, 9(9): e107307

[19]

Gutiérrez D, Vandenheuvel D, Martínez B, Rodríguez A, Lavigne R, García P. (2015). Two phages, phiIPLA-RODI and phiIPLA-C1C, lyse mono-and dual-species staphylococcal biofilms. Applied and Environmental Microbiology, 81(10): 3336–3348

[20]

Howard-Varona C, Hargreaves K R, Abedon S T, Sullivan M B. (2017). Lysogeny in nature: mechanisms, impact and ecology of temperate phages. The ISME Journal, 11(7): 1511–1520

[21]

Hyatt D, Chen G L, LoCascio P F, Land M L, Larimer F W, Hauser L J. (2010). Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics, 11(1): 119

[22]

Jansson J K, Wu R. (2023). Soil viral diversity, ecology and climate change. Nature Reviews Microbiology, 21(5): 296–311

[23]

Kang D D, Li F, Kirton E, Thomas A, Egan R, An H, Wang Z. (2019). MetaBAT 2: an adaptive binning algorithm for robust and efficient genome reconstruction from metagenome assemblies. PeerJ, 7: e7359

[24]

Kelly D, McAuliffe O, Ross R P, Coffey A. (2012). Prevention of Staphylococcus aureus biofilm formation and reduction in established biofilm density using a combination of phage K and modified derivatives. Letters in Applied Microbiology, 54(4): 286–291

[25]

Knecht L E, Veljkovic M, Fieseler L. (2020). Diversity and function of phage encoded depolymerases. Frontiers in Microbiology, 10: 2949

[26]

Koonin E V, Dolja V V, Krupovic M, Varsani A, Wolf Y I, Yutin N, Zerbini F M, Kuhn J H. (2020). Global organization and proposed megataxonomy of the virus world. Microbiology and Molecular Biology Reviews, 84(2): e00061–19

[27]

Koonin E V, Makarova K S, Wolf Y I. (2017). Evolutionary genomics of defense systems in archaea and bacteria. Annual Review of Microbiology, 71: 233–261

[28]

Kunisch F, Campobasso C, Wagemans J, Yildirim S, Chan B K, Schaudinn C, Lavigne R, Turner P E, Raschke M J, Trampuz A. . (2024). Targeting Pseudomonas aeruginosa biofilm with an evolutionary trained bacteriophage cocktail exploiting phage resistance trade-offs. Nature Communications, 15(1): 8572

[29]

Lei Z, Wang J, Leng L W, Yang S M, Dzakpasu M, Li Q, Li Y Y, Wang X C, Chen R. (2021). New insight into the membrane fouling of anaerobic membrane bioreactors treating sewage: physicochemical and biological characterization of cake and gel layers. Journal of Membrane Science, 632: 119383

[30]

Lei Z, Zheng J L, Liu J L, Li Q, Xue J J, Yang Y, Kong Z, Li Y Y, Chen R. (2024). Synergic treatment of domestic wastewater and food waste in an anaerobic membrane bioreactor demo plant: process performance, energy consumption, and greenhouse gas emissions. Water Research, 266: 122371

[31]

Letunic I, Bork P. (2021). Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Research, 49(W1): W293–W296

[32]

Li D H, Liu C M, Luo R B, Sadakane K, Lam T W. (2015). MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph. Bioinformatics, 31(10): 1674–1676

[33]

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, 1000 Genome Project Data Processing Subgroup. (2009). The sequence alignment/map format and SAMtools. Bioinformatics, 25(16): 2078–2079

[34]

Li Q, Hou Z Y, Huang X Y, Yang S M, Zhang J F, Fu J W, Li Y Y, Chen R. (2023). Methanation and chemolitrophic nitrogen removal by an anaerobic membrane bioreactor coupled partial nitrification and Anammox. Frontiers of Environmental Science & Engineering, 17(6): 68

[35]

Li X, Cai T, Amy G L, Chung T S. (2017). Cleaning strategies and membrane flux recovery on anti-fouling membranes for pressure retarded osmosis. Journal of Membrane Science, 522: 116–123

[36]

Liao H P, Liu C, Zhou S G, Liu C Q, Eldridge D J, Ai C F, Wilhelm S W, Singh B K, Liang X L, Radosevich M. . (2024). Prophage-encoded antibiotic resistance genes are enriched in human-impacted environments. Nature Communications, 15(1): 8315

[37]

Liu X, Ye Y, Zhang Z S, Rensing C, Zhou S G, Nealson K H. (2023). Prophage induction causes Geobacter electroactive biofilm decay. Environmental Science & Technology, 57(15): 6196–6204

[38]

Mayorga-Ramos A, Carrera-Pacheco S E, Barba-Ostria C, Guamán L P. (2024). Bacteriophage-mediated approaches for biofilm control. Frontiers in Cellular and Infection Microbiology, 14: 1428637

[39]

Meng F G, Zhang S Q, Oh Y, Zhou Z B, Shin H S, Chae S R. (2017). Fouling in membrane bioreactors: an updated review. Water Research, 114: 151–180

[40]

Miwa T, Takimoto Y, Hatamoto M, Kuratate D, Watari T, Yamaguchi T. (2021). Role of live cell colonization in the biofilm formation process in membrane bioreactors treating actual sewage under low organic loading rate conditions. Applied Microbiology and Biotechnology, 105(4): 1721–1729

[41]

Motlagh A M, Bhattacharjee A S, Goel R. (2015). Microbiological study of bacteriophage induction in the presence of chemical stress factors in enhanced biological phosphorus removal (EBPR). Water Research, 81: 1–14

[42]

Nayfach S, Camargo A P, Schulz F, Eloe-Fadrosh E, Roux S, Kyrpides N C. (2021). CheckV assesses the quality and completeness of metagenome-assembled viral genomes. Nature Biotechnology, 39(5): 578–585

[43]

Niu C X, Zhang Z Y, Cai T, Pan Y, Lu X Q, Zhen G Y. (2024). Sludge bound-EPS solubilization enhance CH4 bioconversion and membrane fouling mitigation in electrochemical anaerobic membrane bioreactor: insights from continuous operation and interpretable machine learning algorithms. Water Research, 264: 122243

[44]

Otawa K, Lee S H, Yamazoe A, Onuki M, Satoh H, Mino T. (2007). Abundance, diversity, and dynamics of viruses on microorganisms in activated sludge processes. Microbial Ecology, 53(1): 143–152

[45]

Parks D H, Imelfort M, Skennerton C T, Hugenholtz P, Tyson G W. (2015). CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Research, 25(7): 1043–1055

[46]

Patel A, Noble R T, Steele J A, Schwalbach M S, Hewson I, Fuhrman J A. (2007). Virus and prokaryote enumeration from planktonic aquatic environments by epifluorescence microscopy with SYBR Green I. Nature Protocols, 2(2): 269–276

[47]

Rastegar S, Skurnik M, Tadjrobehkar O, Samareh A, Samare-Najaf M, Lotfian Z, Khajedadian M, Hosseini-Nave H, Sabouri S. (2024). Synergistic effects of bacteriophage cocktail and antibiotics combinations against extensively drug-resistant Acinetobacter baumannii. BMC Infectious Diseases, 24(1): 1208

[48]

Ren J, Ahlgren N A, Lu Y Y, Fuhrman J A, Sun F Z. (2017). VirFinder: a novel k-mer based tool for identifying viral sequences from assembled metagenomic data. Microbiome, 5(1): 69

[49]

Ren J, Song K, Deng C, Ahlgren N A, Fuhrman J A, Li Y, Xie X H, Poplin R, Sun F Z. (2020). Identifying viruses from metagenomic data using deep learning. Quantitative Biology, 8(1): 64–77

[50]

Roux S, Enault F, Hurwitz B L, Sullivan M B. (2015). VirSorter: mining viral signal from microbial genomic data. PeerJ, 3: e985

[51]

Seviour T, Pijuan M, Nicholson T, Keller J, Yuan Z G. (2009). Gel-forming exopolysaccharides explain basic differences between structures of aerobic sludge granules and floccular sludges. Water Research, 43(18): 4469–4478

[52]

Shang J Y, Jiang J Z, Sun Y N. (2021). Bacteriophage classification for assembled contigs using graph convolutional network. Bioinformatics, 37(S1): i25–i33

[53]

Shang J Y, Sun Y N. (2022). CHERRY: a Computational metHod for accuratE pRediction of virus–pRokarYotic interactions using a graph encoder–decoder model. Briefings in Bioinformatics, 23(5): bbac182

[54]

Shang J Y, Tang X B, Guo R C, Sun Y N. (2022). Accurate identification of bacteriophages from metagenomic data using Transformer. Briefings in Bioinformatics, 23(4): bbac258

[55]

Shang J Y, Tang X B, Sun Y N. (2023). PhaTYP: predicting the lifestyle for bacteriophages using BERT. Briefings in Bioinformatics, 24(1): bbac487

[56]

So B, Kim J, Jo J K, So H. (2024). Recent developments in preventing catheter-related infections based on biofilms: a comprehensive review. Biomicrofluidics, 18(5): 051506

[57]

Suttle C A. (2007). Marine viruses—major players in the global ecosystem. Nature Reviews Microbiology, 5(10): 801–812

[58]

Tamura K, Stecher G, Kumar S. (2021). MEGA11: molecular evolutionary genetics analysis version 11. Molecular Biology and Evolution, 38(7): 3022–3027

[59]

Tan Y X, Yu P F, Huang D, Yuan M M, Yu Z D, Lu H J, Alvarez P J J, Zhu L. (2023). Enhanced bacterium–phage symbiosis in attached microbial aggregates on a membrane surface facing elevated hydraulic stress. Environmental Science & Technology, 57(45): 17324–17337

[60]

Tang X, Fan C Z, Zeng G M, Zhong L R, Li C, Ren X Y, Song B, Liu X G. (2022). Phage-host interactions: the neglected part of biological wastewater treatment. Water Research, 226: 119183

[61]

Tang X, Zhong L R, Tang L, Fan C Z, Zhang B W, Wang M E, Dong H R, Zhou C Y, Rensing C, Zhou S G. . (2023). Lysogenic bacteriophages encoding arsenic resistance determinants promote bacterial community adaptation to arsenic toxicity. The ISME Journal, 17(7): 1104–1115

[62]

The UniProt Consortium. (2019). UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research, 47(D1): D506–D515

[63]

von Meijenfeldt F A B, Arkhipova K, Cambuy D D, Coutinho F H, Dutilh B E. (2019). Robust taxonomic classification of uncharted microbial sequences and bins with CAT and BAT. Genome Biology, 20(1): 217

[64]

Wang R G, Wang T C, Qu G Z, Zhang Y, Guo X T, Jia H Z, Zhu L Y. (2021). Insights into the underlying mechanisms for integrated inactivation of A. spiroides and depression of disinfection byproducts by plasma oxidation. Water Research, 196: 117027

[65]

Wang S Y, Ping Q, Li Y M. (2022). Comprehensively understanding metabolic pathways of protein during the anaerobic digestion of waste activated sludge. Chemosphere, 297: 134117

[66]

Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer F T, de Beer T A P, Rempfer C, Bordoli L. . (2018). SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Research, 46(W1): W296–W303

[67]

Wood D E, Lu J, Langmead B. (2019). Improved metagenomic analysis with Kraken 2. Genome Biology, 20(1): 257

[68]

Yu Y, Xin C C, Liu Y X, Gao F, Zhang L, Jia H, Wang J. (2024). Portable fluorescence instrument for detecting membrane integrity in membrane bioreactor (MBR). Frontiers of Environmental Science & Engineering, 18(2): 23

[69]

Yuan L, Hansen M F, Røder H L, Wang N, Burmølle M, He G Q. (2020). Mixed-species biofilms in the food industry: current knowledge and novel control strategies. Critical Reviews in Food Science and Nutrition, 60(13): 2277–2293

[70]

Yuan L, Ju F. (2023). Potential auxiliary metabolic capabilities and activities reveal biochemical impacts of viruses in municipal wastewater treatment plants. Environmental Science & Technology, 57(13): 5485–5498

[71]

Zang B, Zhou H, Zhao Y B, Sano D, Chen R. (2024). Investigating potential auxiliary anaerobic digestion activity of phage under polyvinyl chloride microplastic stress. Journal of Hazardous Materials, 480: 135950

[72]

Zhang J Y, Gao Q, Zhang Q T, Wang T X, Yue H W, Wu L W, Shi J, Qin Z Y, Zhou J Z, Zuo J N. . (2017). Bacter-iophage–prokaryote dynamics and interaction within anaerobic digestion processes across time and space. Microbiome, 5(1): 57

[73]

Zhang S Q, Meng F G. (2021). Core activated sludge communities are influenced little by immigration: case study of a membrane bioreactor plant. Journal of Environmental Sciences, 102: 244–255

[74]

Zheng X X, Jahn M T, Sun M M, Friman V P, Balcazar J L, Wang J F, Shi Y, Gong X, Hu F, Zhu Y G. (2022). Organochlorine contamination enriches virus-encoded metabolism and pesticide degradation associated auxiliary genes in soil microbiomes. The ISME Journal, 16(5): 1397–1408

[75]

Zhou Z B, Meng F G, He X, Chae S R, An Y J, Jia X S. (2015). Metaproteomic analysis of biocake proteins to understand membrane fouling in a submerged membrane bioreactor. Environmental Science & Technology, 49(2): 1068–1077

[76]

Zuo P X, Metz J, Yu P F, Alvarez P J J. (2022). Biofilm-responsive encapsulated-phage coating for autonomous biofouling mitigation in water storage systems. Water Research, 224: 119070

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