Current perspectives on multi-omics studies of bacteria from the Bacteroides group
Main Article Content
Abstract
This review discusses multi-omics (genomic, transcriptomic, and proteomic) approaches for studying bacteria of the Bacteroides spp. group, which are the most common anaerobes in the human colon and are responsible for over half of all intra-abdominal anaerobic infections. These multi-omics approaches have enabled the identification of virulence factors, antimicrobial resistance genes, and other functional elements of the Bacteroides genome. This information is crucial for understanding the pathogenic potential of these bacteria and their role in the development of anaerobic infections. This review examines the transcriptional response of Bacteroides after exposure to sub-inhibitory concentrations of antimicrobial drugs, as well as the main methods of proteomic analysis and achievements in studying the Bacteroides proteome. Overall, the modern perspectives of multi-omics studies on Bacteroides emphasize the possibility of integrating different omics approaches for a more comprehensive understanding of their biology, functional characteristics, and ecological roles in the gut ecosystem.
Article Details
Accepted 2025-09-20
Published 2025-09-22
References
Wexler H.M. Bacteroides: the good, the bad, and the nitty-gritty // Clinical Microbiology Re-views. – 2007. – Vol. 20. – P. 593–621. https://doi.org/10.1128/CMR.00008-07.
Glowacki R.W.P., Pudlo N.A., Tuncil Y., Luis A.S., Sajjakulnukit P., Terekhov A.I., Lyssiotis C.A., Hamaker B.R., Martens E.C. A ribose-scavenging system confers colonization fitness on the human gut symbiont Bacteroides thetaiotaomicron in a diet-specific manner // Cell Host & Microbe. – 2020. – Vol. 27. – P. 79–92.e9. https://doi.org/10.1016/j.chom.2019.11.009.
Buffie C.G., Pamer E.G. Microbiota-mediated colonization resistance against intestinal path-ogens // Nature Reviews Immunology. – 2013. – Vol. 13. – P. 790–801. https://doi.org/10.1038/nri3535.
Prezza G., Ryan D., Mädler G., Reichardt S., Barquist L., Westermann A.J. Comparative ge-nomics provides structural and functional insights into Bacteroides RNA biology // Molecular Microbi-ology. – 2022. – Vol. 117. – P. 67–85. https://doi.org/10.1111/mmi.14793.
Valdezate S., Cobo F., Monzón S., Medina-Pascual M.J., Zaballos Á., Cuesta I., Pino-Rosa S., Villalón P. Genomic background and phylogeny of cfiA-positive Bacteroides fragilis strains resistant to meropenem-EDTA // Antibiotics (Basel). – 2021. – Vol. 10. – Article No. 304. https://doi.org/10.3390/antibiotics10030304.
Niestępski S., Harnisz M., Korzeniewska E., Aguilera-Arreola M.G., Contreras-Rodríguez A., Filipkowska Z., Osińska A. The emergence of antimicrobial resistance in environmental strains of the Bacteroides fragilis group // Environment International. – 2019. – Vol. 124. – P. 408–419. https://doi.org/10.1016/j.envint.2018.12.056.
Wang Y., Guo B., Gao X., Wen J., Wang Z., Wang J. High prevalence of cfiA-positive Bacteroides fragilis isolates collected at a teaching hospital in Hohhot, China // Anaerobe. – 2023. – Vol. 79. – Article No. 102691. https://doi.org/10.1016/j.anaerobe.2022.102691.
El-Gamal M.I., Brahim I., Hisham N., Aladdin R., Mohammed H., Bahaaeldin A. Recent up-dates of carbapenem antibiotics // European Journal of Medicinal Chemistry. – 2017. – Vol. 131. – P. 185–195. https://doi.org/10.1016/j.ejmech.2017.03.022.
Tran C.M., Tanaka K., Yamagishi Y., Goto T., Mikamo H., Watanabe K. In vitro antimicrobial activity of razupenem (SMP-601, PTZ601) against anaerobic bacteria // Antimicrobial Agents and Chemotherapy. – 2011. – Vol. 55. – P. 2398–2402. https://doi.org/10.1128/AAC.01038-10.
Tanaka K., Mikamo H., Nakao K., Ichiishi T., Goto T., Yamagishi Y., Watanabe K. In vitro activity of tomopenem (CS−023/RO4908463) against anaerobic bacteria // Antimicrobial Agents and Chemotherapy. – 2009. – Vol. 53. – P. 319–322. https://doi.org/10.1128/AAC.00595-08.
Yekani M., Rezaee M.A., Beheshtirouy S., Baghi H.B., Bazmani A., Farzinazar A., Memar M.Y., Sóki J. Carbapenem resistance in Bacteroides fragilis: a review of molecular mechanisms // An-aerobe. – 2022. – Vol. 76. – Article No. 102606. https://doi.org/10.1016/j.anaerobe.2022.102606.
Masterton R.G. The new treatment paradigm and the role of carbapenems // International Journal of Antimicrobial Agents. – 2009. – Vol. 33. – P. 105–110. https://doi.org/10.1016/j.ijantimicag.2008.07.023.
Zhanel G.G., Wiebe R., Dilay L., Thomson K., Rubinstein E., Hoban D.J., Noreddin A.M., Karlowsky J.A. Comparative review of the carbapenems // Drugs. – 2007. – Vol. 67. – P. 1027–1052. https://doi.org/10.2165/00003495-200767070-00006.
Papp-Wallace K.M., Endimiani A., Taracila M.A., Bonomo R.A. Carbapenems: Past, Present, and Future // Antimicrobial Agents and Chemotherapy. – 2011. – Vol. 55. – P. 4943–4960. https://doi.org/10.1128/AAC.00296-11.
Pumbwe L., Ueda O., Yoshimura F., Chang A., Smith R.L., Wexler H.M. Bacteroides fragilis BmeABC efflux systems additively confer intrinsic antimicrobial resistance // Journal of Antimicrobial Chemotherapy. – 2006. – Vol. 58. – P. 37–46. https://doi.org/10.1093/jac/dkl202.
Ghotaslou R., Yekani M., Memar M.Y. The role of efflux pumps in Bacteroides fragilis re-sistance to antibiotics // Microbiological Research. – 2018. – Vol. 210. – P. 1–5. https://doi.org/10.1016/j.micres.2018.02.007.
Wallace M.J., Jean S., Wallace M.A., Burnham C.-A.D., Dantas G. Comparative genomics of Bacteroides fragilis group isolates reveals species-dependent resistance mechanisms and validates clinical tools for resistance prediction // mBio. – 2022. – Vol. 13. – Article No. e0360321. https://doi.org/10.1128/mbio.03603-21.
Nagy E., Becker S., Sóki J., Urbán E., Kostrzewa M. Differentiation of division I (cfiA-negative) and division II (cfiA-positive) Bacteroides fragilis strains by matrix-assisted laser de-sorption/ionization time-of-flight mass spectrometry // Journal of Medical Microbiology. – 2011. – Vol. 60. – P. 1584–1590. https://doi.org/10.1099/jmm.0.031336-0.
Holmqvist E., Wagner E.G.H. Impact of bacterial sRNAs in stress responses // Biochemical Society Transactions. – 2017. – Vol. 45. – P. 1203–1212. https://doi.org/10.1042/BST20160363.
Ryan D., Jenniches L., Reichardt S., Barquist L., Westermann A.J. A high-resolution transcriptome map identifies small RNA regulation of metabolism in the gut microbe Bacteroides thetaiotaomicron // Nature Communications. – 2020. – Vol. 11. – Article No. 3557. https://doi.org/10.1038/s41467-020-17348-5.
Kavita K., de Mets F., Gottesman S. New aspects of RNA-based regulation by Hfq and its partner sRNAs // Current Opinion in Microbiology. – 2018. – Vol. 42. – P. 53–61. https://doi.org/10.1016/j.mib.2017.10.014.
Olejniczak M., Storz G. ProQ/FinO-domain proteins: another ubiquitous family of RNA matchmakers? // Molecular Microbiology. – 2017. – Vol. 104. – P. 905–915. https://doi.org/10.1111/mmi.13679.
Adams A.N.D., Azam M.S., Costliow Z.A., Ma X., Degnan P.H., Vanderpool C.K. A novel family of RNA-binding proteins regulate polysaccharide metabolism in Bacteroides thetaiotaomicron // Journal of Bacteriology. – 2021. – Vol. 203. – Article No. e0021721. https://doi.org/10.1128/JB.00217-21.
Cao H., Liu M.C.-J., Tong M.K., Jiang S., Chow K.H., To K.K.-W., Tse C.W., Ho P.L. Comprehensive investigation of antibiotic resistance gene content in cfiA-harboring Bacteroides fragilis isolates of human and animal origins by whole genome sequencing // International Journal of Medical Microbiology. – 2022. – Vol. 312. – Article No. 151559. https://doi.org/10.1016/j.ijmm.2022.151559.
Veeranagouda Y., Husain F., Tenorio E.L., Wexler H.M. Identification of genes required for the survival of Bacteroides fragilis using massive parallel sequencing of a saturated transposon mutant library // BMC Genomics. – 2014. – Vol. 15. – Article No. 429. https://doi.org/10.1186/1471-2164-15-429.
El-Gebali S., Mistry J., Bateman A., Eddy S.R., Luciani A., Potter S.C., Qureshi M., Rich-ardson L.J., Salazar G.A., Smart A., et al. The Pfam protein families database in 2019 // Nucleic Acids Research. – 2019. – Vol. 47. – P. D427–D432. https://doi.org/10.1093/nar/gky995.
Romeo T., Babitzke P. Global regulation by CsrA and its RNA antagonists // Microbiology Spectrum. – 2018. – Vol. 6. https://doi.org/10.1128/microbiolspec.RWR-0009-2017.
Maris C., Dominguez C., Allain F.H.T. The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression // FEBS Journal. – 2005. – Vol. 272. – P. 2118–2131. https://doi.org/10.1111/j.1742-4658.2005.04653.x.
Nicastro G., Taylor I.A., Ramos A. KH−RNA interactions: back in the groove // Current Opinion in Structural Biology. – 2015. – Vol. 30. – P. 63–70. https://doi.org/10.1016/j.sbi.2015.01.002.
Phadtare S., Severinov K. RNA remodeling and gene regulation by cold shock proteins // RNA Biology. – 2010. – Vol. 7. – P. 788–795. https://doi.org/10.4161/rna.7.6.13482.
Ryan D., Prezza G., Westermann A.J. An RNA-centric view on gut Bacteroidetes // Biological Chemistry. – 2020. – Vol. 402. – P. 55–72. https://doi.org/10.1515/hsz-2020-0230.
Waters J.L., Salyers A.A. The small RNA RteR inhibits transfer of the Bacteroides conjugative transposon CTnDOT // Journal of Bacteriology. – 2012. – Vol. 194. – P. 5228–5236. https://doi.org/10.1128/JB.00941-12.
Diniz C.G., Farias L.M., Carvalho M.A.R., Rocha E.R., Smith C.J. Differential gene expression in a Bacteroides fragilis metronidazole-resistant mutant // Journal of Antimicrobial Chemotherapy. – 2004. – Vol. 54. – P. 100–108. https://doi.org/10.1093/jac/dkh256.
Freitas M.C.R., Silva V.L., Gameiro J., Ferreira-Machado A.B., Coelho C.M., Cara D.C., Diniz C.G. Bacteroides fragilis response to subinhibitory concentrations of antimicrobials includes different morphological, physiological and virulence patterns after in vitro selection // Microbial Pathogenesis. – 2015. – Vol. 78. – P. 103–113. https://doi.org/10.1016/j.micpath.2014.12.002.
de Freitas M.C.R., Resende J.A., Ferreira-Machado A.B., Saji G.D.R.Q., de Vasconcelos A.T.R., da Silva V.L., Nicolás M.F., Diniz C.G. Exploratory investigation of Bacteroides fragilis tran-scriptional response during in vitro exposure to subinhibitory concentration of metronidazole // Frontiers in Microbiology. – 2016. – Vol. 7. – Article No. 1465. https://doi.org/10.3389/fmicb.2016.01465.
Davies J., Spiegelman G.B., Yim G. The world of subinhibitory antibiotic concentrations // Current Opinion in Microbiology. – 2006. – Vol. 9. – P. 445–453. https://doi.org/10.1016/j.mib.2006.08.006.
Wang Y., Rotman E.R., Shoemaker N.B., Salyers A.A. Translational control of tetracycline resistance and conjugation in the Bacteroides conjugative transposon CTnDOT // Journal of Bacteriology. – 2005. – Vol. 187. – P. 2673–2680. https://doi.org/10.1128/JB.187.8.2673-2680.2005.
Fitzpatrick F., Humphreys H., Smyth E., Kennedy C.A., O’Gara J.P. Environmental regulation of biofilm formation in intensive care unit isolates of Staphylococcus epidermidis // Journal of Hospital Infection. – 2002. – Vol. 52. – P. 212–218. https://doi.org/10.1053/jhin.2002.1309.
Tanaka M., Hasegawa T., Okamoto A., Torii K., Ohta M. Effect of antibiotics on group A Streptococcus exoprotein production analyzed by two-dimensional gel electrophoresis // Antimicrobial Agents and Chemotherapy. – 2005. – Vol. 49. – P. 88–96. https://doi.org/10.1128/AAC.49.1.88-96.2005.
Cerca N., Martins S., Sillankorva S., Jefferson K.K., Pier G.B., Oliveira R., Azeredo J. Effects of growth in the presence of subinhibitory concentrations of dicloxacillin on Staphylococcus epidermidis and Staphylococcus haemolyticus biofilms // Applied and Environmental Microbiology. – 2005. – Vol. 71. – P. 8677–8682. https://doi.org/10.1128/AEM.71.12.8677-8682.2005.
Adhikari R.P., Novick R.P. Subinhibitory cerulenin inhibits staphylococcal exoprotein pro-duction by blocking transcription rather than by blocking secretion // Microbiology (Reading). – 2005. – Vol. 151. – P. 3059–3069. https://doi.org/10.1099/mic.0.28102-0.
Hoffman L.R., D’Argenio D.A., MacCoss M.J., Zhang Z., Jones R.A., Miller S.I. Amino-glycoside antibiotics induce bacterial biofilm formation // Nature. – 2005. – Vol. 436. – P. 1171–1175. https://doi.org/10.1038/nature03912.
Henderson-Begg S.K., Livermore D.M., Hall L.M.C. Effect of subinhibitory concentrations of antibiotics on mutation frequency in Streptococcus pneumoniae // Journal of Antimicrobial Chemotherapy. – 2006. – Vol. 57. – P. 849–854. https://doi.org/10.1093/jac/dkl064.
Jerman B., Butala M., Zgur-Bertok D. Sublethal concentrations of ciprofloxacin induce bacteriocin synthesis in Escherichia coli // Antimicrobial Agents and Chemotherapy. – 2005. – Vol. 49. – P. 3087–3090. https://doi.org/10.1128/AAC.49.7.3087-3090.2005.
Li D., Renzoni A., Estoppey T., Bisognano C., Francois P., Kelley W.L., Lew D.P., Schrenzel J., Vaudaux P. Induction of fibronectin adhesins in quinolone-resistant Staphylococcus aureus by subinhibitory levels of ciprofloxacin or by sigma B transcription factor activity is mediated by two separate pathways // Antimicrobial Agents and Chemotherapy. – 2005. – Vol. 49. – P. 916–924. https://doi.org/10.1128/AAC.49.3.916-924.2005.
Gillespie S.H., Basu S., Dickens A.L., O’Sullivan D.M., McHugh T.D. Effect of subinhibitory concentrations of ciprofloxacin on Mycobacterium fortuitum mutation rates // Journal of Antimicrobial Chemotherapy. – 2005. – Vol. 56. – P. 344–348. https://doi.org/10.1093/jac/dki191.
Carter G., Young L.S., Bermudez L.E. A subinhibitory concentration of clarithromycin inhibits Mycobacterium avium biofilm formation // Antimicrobial Agents and Chemotherapy. – 2004. – Vol. 48. – P. 4907–4910. https://doi.org/10.1128/AAC.48.12.4907-4910.2004.
Nalca Y., Jänsch L., Bredenbruch F., Geffers R., Buer J., Häussler S. Quorum-sensing an-tagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: a global approach // Antimicrobial Agents and Chemotherapy. – 2006. – Vol. 50. – P. 1680–1688. https://doi.org/10.1128/AAC.50.5.1680-1688.2006.
Silvestro E.M., Nakano V., Arana-Chavez V.E., Marques M.V., Avila-Campos M.J. Effects of subinhibitory concentrations of clindamycin on the morphological, biochemical and genetic characteristics of Bacteroides fragilis // FEMS Microbiology Letters. – 2006. – Vol. 257. – P. 189–194. https://doi.org/10.1111/j.1574-6968.2006.00162.x.
Bernardo K., Pakulat N., Fleer S., Schnaith A., Utermöhlen O., Krut O., Müller S., Krönke M. Subinhibitory concentrations of linezolid reduce Staphylococcus aureus virulence factor expression // Antimicrobial Agents and Chemotherapy. – 2004. – Vol. 48(2). – P. 546–555. https://doi.org/10.1128/AAC.48.2.546-555.2004.
Ishikawa J., Horii T. Effects of mupirocin at subinhibitory concentrations on biofilm formation in Pseudomonas aeruginosa // Chemotherapy. – 2005. – Vol. 51. – P. 361–362. https://doi.org/10.1159/000088962.
Matar G.M., Rahal E. Inhibition of the transcription of the Escherichia coli O157:H7 genes coding for shiga-like toxins and intimin, and its potential use in the treatment of human infection with the bacterium // Annals of Tropical Medicine and Parasitology. – 2003. – Vol. 97. – P. 281–287. https://doi.org/10.1179/000349803235002146.
Boente R.F., Pauer H., Silva D.N.S., Filho J.S., Sandim V., Antunes L.C.M., Ferreira R.B., Zingali R.B., Domingues R.M., Lobo L.A. Differential proteomic analysis of outer membrane enriched extracts of Bacteroides fragilis grown under bile salts stress // Anaerobe. – 2016. – Vol. 39. – P. 84–90. https://doi.org/10.1016/j.anaerobe.2016.03.003.
Rios-Covián D., Sánchez B., Martínez N., Cuesta I., Hernández-Barranco A.M., de los Reyes-Gavilán C.G., Gueimonde M. A proteomic approach towards understanding the cross talk between Bacteroides fragilis and Bifidobacterium longum in coculture // Canadian Journal of Microbiology. – 2016. – Vol. 62. – P. 623–628. https://doi.org/10.1139/cjm-2015-0804.
Veloso L.C., dos Santos K.V., de Andrade H.M., Pires S.F., dos Santos S.G., Vaz Trindade M.J., de Farias L.M., de Carvalho M.A. Proteomic changes in Bacteroides fragilis exposed to subinhibitory concentration of piperacillin/tazobactam // Anaerobe. – 2013. – Vol. 22. – P. 69–76. https://doi.org/10.1016/j.anaerobe.2013.04.007.
Jeverica S., Sóki J., Premru M.M., Nagy E., Papst L. High prevalence of division II (cfiA-positive) isolates among bloodstream Bacteroides fragilis in Slovenia as determined by MALDI-TOF MS // Anaerobe. – 2019. – Vol. 58. – P. 30–34. https://doi.org/10.1016/j.anaerobe.2019.01.011.
Kawamoto Y., Kosai K., Ota K., Uno N., Sakamoto K., Hasegawa H., Izumikawa K., Mukae H., Yanagihara K. Rapid detection and surveillance of cfiA-positive Bacteroides fragilis using ma-trix-assisted laser desorption ionization time-of-flight mass spectrometry // Anaerobe. – 2021. – Vol. 72. – 102448. https://doi.org/10.1016/j.anaerobe.2021.102448.
Hashimoto T., Hashinaga K., Komiya K., Hiramatsu K. Prevalence of antimicrobial resistant genes in Bacteroides spp. isolated in Oita Prefecture, Japan // Journal of Infection and Chemotherapy. – 2023. – Vol. 29. – P. 284–288. https://doi.org/10.1016/j.jiac.2022.11.011.
Treviño M., Areses P., Peñalver M.D., Cortizo S., Pardo F., del Molino M.L.P., García-Riestra C., Hernández M., Llovo J., Regueiro B.J. Susceptibility trends of Bacteroides fragilis group and char-acterisation of carbapenemase-producing strains by automated REP-PCR and MALDI TOF // Anaerobe. – 2012. – Vol. 18. – P. 37–43. https://doi.org/10.1016/j.anaerobe.2011.12.022.