Lipid A in outer membrane vesicles shields bacteria from polymyxins.
Klebsiella pneumoniae
/ metabolism
Anti-Bacterial Agents
/ pharmacology
Animals
Polymyxin B
/ pharmacology
Bacterial Outer Membrane
/ metabolism
Polymyxins
/ pharmacology
Extracellular Vesicles
/ metabolism
Klebsiella Infections
/ microbiology
Microbial Sensitivity Tests
Drug Resistance, Multiple, Bacterial
/ drug effects
antimicrobial peptides (AMP)
bacterial extracellular vesicles
bacterial resistance mechanisms
last‐resort antibiotic
lipid A
multi‐drug resistance (MDR)
polymyxins
Journal
Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479
Informations de publication
Date de publication:
May 2024
May 2024
Historique:
revised:
18
04
2024
received:
17
01
2024
accepted:
23
04
2024
medline:
20
5
2024
pubmed:
20
5
2024
entrez:
20
5
2024
Statut:
ppublish
Résumé
The continuous emergence of multidrug-resistant bacterial pathogens poses a major global healthcare challenge, with Klebsiella pneumoniae being a prominent threat. We conducted a comprehensive study on K. pneumoniae's antibiotic resistance mechanisms, focusing on outer membrane vesicles (OMVs) and polymyxin, a last-resort antibiotic. Our research demonstrates that OMVs protect bacteria from polymyxins. OMVs derived from Polymyxin B (PB)-stressed K. pneumoniae exhibited heightened protective efficacy due to increased vesiculation, compared to OMVs from unstressed Klebsiella. OMVs also shield bacteria from different bacterial families. This was validated ex vivo and in vivo using precision cut lung slices (PCLS) and Galleria mellonella. In all models, OMVs protected K. pneumoniae from PB and reduced the associated stress response on protein level. We observed significant changes in the lipid composition of OMVs upon PB treatment, affecting their binding capacity to PB. The altered binding capacity of single OMVs from PB stressed K. pneumoniae could be linked to a reduction in the lipid A amount of their released vesicles. Although the amount of lipid A per vesicle is reduced, the overall increase in the number of vesicles results in an increased protection because the sum of lipid A and therefore PB binding sites have increased. This unravels the mechanism of the altered PB protective efficacy of OMVs from PB stressed K. pneumoniae compared to control OMVs. The lipid A-dependent protective effect against PB was confirmed in vitro using artificial vesicles. Moreover, artificial vesicles successfully protected Klebsiella from PB ex vivo and in vivo. The findings indicate that OMVs act as protective shields for bacteria by binding to polymyxins, effectively serving as decoys and preventing antibiotic interaction with the cell surface. Our findings provide valuable insights into the mechanisms underlying antibiotic cross-protection and offer potential avenues for the development of novel therapeutic interventions to address the escalating threat of multidrug-resistant bacterial infections.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12447Subventions
Organisme : Hessisches Ministerium für Wissenschaft und Kunst
ID : LOEWE/2/13/519/03/06.001(0002)/74
Organisme : Deutsche Forschungsgemeinschaft
ID : 512453064
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB/TR-84 TP C01
Organisme : von Behring-Röntgen-Stiftung
ID : 66-LV07
Organisme : von Behring-Röntgen-Stiftung
ID : 71_0002
Organisme : German Center for Lung Research (DZL)
Organisme : German Ministry for Education and Research (BMBF)
ID : ERACo-SysMed2 SysMed-COPD-FKZ 031L0140
Organisme : German Ministry for Education and Research (BMBF)
ID : JPIAMR Pneumo-AMRProtect-FKZ 01KI702
Organisme : German Ministry for Education and Research (BMBF)
ID : e:Med CAPSYS-FKZ 01X1304E/01ZX1304F
Informations de copyright
© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.
Références
Ahrné, E., Molzahn, L., Glatter, T., & Schmidt, A. (2013). Critical assessment of proteome‐wide label‐free absolute abundance estimation strategies. Proteomics, 13(17), 2567–2578. https://doi.org/10.1002/pmic.201300135
Arnold, U., & Ulbrich‐Hofmann, R. (1999). Quantitative protein precipitation from guanidine hydrochloride‐containing solutions by sodium deoxycholate/trichloroacetic acid. Analytical Biochemistry, 271(2), 197–199. https://doi.org/10.1006/abio.1999.4149
Ayoub Moubareck, C. (2020). Polymyxins and bacterial membranes: A review of antibacterial activity and mechanisms of resistance. Membranes, 10(8), 181. https://doi.org/10.3390/membranes10080181
Bassetti, M., Righi, E., Carnelutti, A., Graziano, E., & Russo, A. (2018). Multidrug‐resistant Klebsiella pneumoniae: Challenges for treatment, prevention and infection control. Expert Review of Anti‐Infective Therapy, 16(10), 749–761. https://doi.org/10.1080/14787210.2018.1522249
Bekker‐Jensen, D. B., Martínez‐Val, A., Steigerwald, S., Rüther, P., Fort, K. L., Arrey, T. N., Harder, A., Makarov, A., & Olsen, J. V. (2020). A compact quadrupole‐orbitrap mass spectrometer with FAIMS interface improves proteome coverage in short LC Gradients. Molecular & Cellular Proteomics: MCP, 19(4), 716–729. https://doi.org/10.1074/mcp.TIR119.001906
Bhar, S., Edelmann, M. J., & Jones, M. K. (2021). Characterization and proteomic analysis of outer membrane vesicles from a commensal microbe, Enterobacter cloacae. Journal of Proteomics, 231, 103994. https://doi.org/10.1016/j.jprot.2020.103994
Bierwagen, J., Wiegand, M., Laakmann, K., Danov, O., Limburg, H., Herbel, S. M., Heimerl, T., Dorna, J., Jonigk, D., Preußer, C., Bertrams, W., Braun, A., Sewald, K., Schulte, L. N., Bauer, S., Pogge von Strandmann, E., Böttcher‐Friebertshäuser, E., Schmeck, B., & Jung, A. L. (2023). Bacterial vesicles block viral replication in macrophages via TLR4‐TRIF‐axis. Cell Communication and Signaling: CCS, 21(1), 65. https://doi.org/10.1186/s12964‐023‐01086‐4
Bush, L. M., & Vazquez‐Pertejo, M. T. (2022). Klebsiella‐, Enterobacter‐ und Serratia‐infektionen. Hg. v. MSD Manual. Online verfügbar unter https://www.msdmanuals.com/de‐de/profi/infektionskrankheiten/gramnegative‐bakterien/und‐infektionen#:~:text=Therapie,‐Antibioti‐ka%20basierend%20auf&text=Die%20Therapie%20erfolgt%20mit%20Cephalosporinen,sind%2C%20ist%20eine%20Empfindlichkeitstestung%20erforderlich, zuletzt geprüft am 21.06.2023
Cahill, B. K., Seeley, K. W., Gutel, D., & Ellis, T. N. (2015). Klebsiella pneumoniae O antigen loss alters the outer membrane protein composition and the selective packaging of proteins into secreted outer membrane vesicles. Microbiological Research, 180, 1–10. https://doi.org/10.1016/j.micres.2015.06.012
Caruana, J. C., & Walper, S. A. (2020). Bacterial membrane vesicles as mediators of microbe—Microbe and microbe—Host community interactions. Frontiers in Microbiology, 11, 432. https://doi.org/10.3389/fmicb.2020.00432
Cheng, H. Y., Chen, Y. S., Wu, C. Y., Chang, H. Y., Lai, Y. C., & Peng, H. L. (2010). RmpA regulation of capsular polysaccharide biosynthesis in Klebsiella pneumoniae CG43. Journal of Bacteriology, 192(12), 3144–3158. https://doi.org/10.1128/JB.00031‐10
Ciofu, O., Beveridge, T. J., Kadurugamuwa, J., Walther‐Rasmussen, J., & Høiby, N. (2000). Chromosomal beta‐lactamase is packaged into membrane vesicles and secreted from Pseudomonas aeruginosa. The Journal of Antimicrobial Chemotherapy, 45(1), 9–13. https://doi.org/10.1093/jac/45.1.9
Dell'Annunziata, F., Dell'Aversana, C., Doti, N., Donadio, G., Dal Piaz, F., Izzo, V., De Filippis, A., Galdiero, M., Altucci, L., Boccia, G., Galdiero, M., Folliero, V., & Franci, G. (2021). Outer membrane vesicles derived from Klebsiella pneumoniae are a driving force for horizontal gene transfer. International Journal of Molecular Sciences, 22(16), 8732. https://doi.org/10.3390/ijms22168732
Demichev, V., Messner, C. B., Vernardis, S. I., Lilley, K. S., & Ralser, M. (2020). DIA‐NN: Neural networks and interference correction enable deep proteome coverage in high throughput. Nature Methods, 17(1), 41–44. https://doi.org/10.1038/s41592‐019‐0638‐x
Dhital, S., Deo, P., Bharathwaj, M., Horan, K., Nickson, J., Azad, M., Stuart, I., Chow, S. H., Gunasinghe, S. D., Bamert, R., Li, J., Lithgow, T., Howden, B. P., & Naderer, T. (2022). Neisseria gonorrhoeae‐derived outer membrane vesicles package β‐lactamases to promote antibiotic resistance. microLife, 3, uqac013. https://doi.org/10.1093/femsml/uqac013
Ellis, T. N., & Kuehn, M. J. (2010). Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiology and Molecular Biology Reviews: MMBR, 74(1), 81–94. https://doi.org/10.1128/MMBR.00031‐09
Fang, C. T., Chuang, Y. P., Shun, C. T., Chang, S. C., & Wang, J. T. (2004). A novel virulence gene in Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. The Journal of Experimental Medicine, 199(5), 697–705. https://doi.org/10.1084/jem.20030857
Fulsundar, S., Harms, K., Flaten, G. E., Johnsen, P. J., Chopade, B. A., & Nielsen, K. M. (2014). Gene transfer potential of outer membrane vesicles of Acinetobacter baylyi and effects of stress on vesiculation. Applied and Environmental Microbiology, 80(11), 3469–3483. https://doi.org/10.1128/AEM.04248‐13
Glatter, T., Ludwig, C., Ahrné, E., Aebersold, R., Heck, A. J., & Schmidt, A. (2012). Large‐scale quantitative assessment of different in‐solution protein digestion protocols reveals superior cleavage efficiency of tandem Lys‐C/trypsin proteolysis over trypsin digestion. Journal of Proteome Research, 11(11), 5145–5156. https://doi.org/10.1021/pr300273g
Gontijo, A. V. L., & Cavalieri, A. V. G. (2021). Optimal control for colistin dosage selection. Journal of Pharmacokinetics and Pharmacodynamics, 48(6), 803–813. https://doi.org/10.1007/s10928‐021‐09769‐6
Groisman, E. A. (2001). The pleiotropic two‐component regulatory system PhoP‐PhoQ. Journal of Bacteriology, 183(6), 1835–1842. https://doi.org/10.1128/JB.183.6.1835‐1842.2001
Gunn, J. S., Ryan, S. S., Van Velkinburgh, J. C., Ernst, R. K., & Miller, S. I. (2000). Genetic and functional analysis of a PmrA‐PmrB‐regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of Salmonella enterica serovar typhimurium. Infection and Immunity, 68(11), 6139–6146. https://doi.org/10.1128/IAI.68.11.6139‐6146.2000
Haeili, M., Javani, A., Moradi, J., Jafari, Z., Feizabadi, M. M., & Babaei, E. (2017). MgrB alterations mediate colistin resistance in Klebsiella pneumoniae isolates from Iran. Frontiers in Microbiology, 8, 2470. https://doi.org/10.3389/fmicb.2017.02470
Hamdi, B., Moussa, I., Berraies, A., Touil, A., Ammar, J., & Hamzaoui, A. (2016). Exacerbations of bronchiectasis: Etiology and outcome. In: 1.5 diffuse parenchymal lung disease. ERS International Congress 2016 abstracts: European Respiratory Society, PA3906.
Hygienemaßnahmen bei Infektionen oder Besiedlung mit multiresistenten gramnegativen Stäbchen. (2012). Empfehlung der Kommission für Kranken‐haushygiene und Infektionsprävention (KRINKO) beim Robert Koch‐Institut (RKI). Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, 55(10), 1311–1354.
Jasim, R., Han, M. L., Zhu, Y., Hu, X., Hussein, M. H., Lin, Y. W., Zhou, Q. T., Dong, C. Y. D., Li, J., & Velkov, T. (2018). Lipidomic analysis of the outer membrane vesicles from paired polymyxin‐susceptible and ‐resistant Klebsiella pneumoniae clinical isolates. International Journal of Molecular Sciences, 19(8), 2356. https://doi.org/10.3390/ijms19082356
Johnston, E. L., Zavan, L., Bitto, N. J., Petrovski, S., Hill, A. F., & Kaparakis‐Liaskos, M. (2023). Planktonic and biofilm‐derived Pseudomonas aeruginosa outer membrane vesicles facilitate horizontal gene transfer of plasmid DNA. Microbiology Spectrum, 11(2), e0517922. Advance online publication. https://doi.org/10.1128/spectrum.05179‐22
Jung, A. L., Herkt, C. E., Schulz, C., Bolte, K., Seidel, K., Scheller, N., Sittka‐Stark, A., Bertrams, W., & Schmeck, B. (2017). Legionella pneumophila infection activates bystander cells differentially by bacterial and host cell vesicles. Scientific Reports, 7(1), 6301. https://doi.org/10.1038/s41598‐017‐06443‐1
Jung, A. L., Stoiber, C., Herkt, C. E., Schulz, C., Bertrams, W., & Schmeck, B. (2016). Legionella pneumophila‐derived outer membrane vesicles promote bacterial replication in macrophages. PLoS Pathogens, 12(4), e1005592. https://doi.org/10.1371/journal.ppat.1005592
Kim, S. W., Lee, J. S., Park, S. B., Lee, A. R., Jung, J. W., Chun, J. H., Lazarte, J. M. S., Kim, J., Seo, J. S., Kim, J. H., Song, J. W., Ha, M. W., Thompson, K. D., Lee, C. R., Jung, M., & Jung, T. S. (2020). The importance of porins and β‐lactamase in outer membrane vesicles on the hydrolysis of β‐lactam antibiotics. International Journal of Molecular Sciences, 21(8), 2822. https://doi.org/10.3390/ijms21082822
Kulkarni, H. M., Nagaraj, R., & Jagannadham, M. V. (2015). Protective role of E. coli outer membrane vesicles against antibiotics. Microbiological Research, 181, 1–7. https://doi.org/10.1016/j.micres.2015.07.008
Kulp, A., & Kuehn, M. J. (2010). Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annual Review of Microbiology, 64, 163–184. https://doi.org/10.1146/annurev.micro.091208.073413
Li, J., Nation, R. L., Milne, R. W., Turnidge, J. D., & Coulthard, K. (2005). Evaluation of colistin as an agent against multi‐resistant Gram‐negative bacteria. International Journal of Antimicrobial Agents, 25(1), 11–25. https://doi.org/10.1016/j.ijantimicag.2004.10.001
Li, L., & Huang, H. (2017). Risk factors of mortality in bloodstream infections caused by Klebsiella pneumonia: A single‐center retrospective study in China. Medicine, 96(35), e7924. https://doi.org/10.1097/MD.0000000000007924
Liu, J., Hsieh, C. L., Gelincik, O., Devolder, B., Sei, S., Zhang, S., Lipkin, S. M., & Chang, Y. F. (2019). Proteomic characterization of outer membrane vesicles from gut mucosa‐derived Fusobacterium nucleatum. Journal of Proteomics, 195, 125–137. https://doi.org/10.1016/j.jprot.2018.12.029
Liu, Y., Liu, P. P., Wang, L. H., Wei, D. D., Wan, L. G., & Zhang, W. (2017). Capsular polysaccharide types and virulence‐related traits of epidemic KPC‐producing Klebsiella pneumoniae isolates in a Chinese University Hospital. Microbial Drug Resistance (Larchmont, N.Y.), 23(7), 901–907. https://doi.org/10.1089/mdr.2016.0222
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real‐time quantitative PCR and the 2(‐Delta Delta C(T)) method. Methods (San Diego, Calif.), 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262
Macdonald, I. A., & Kuehn, M. J. (2013). Stress‐induced outer membrane vesicle production by Pseudomonas aeruginosa. Journal of Bacteriology, 195(13), 2971–2981. https://doi.org/10.1128/JB.02267‐12
Maestre‐Carballa, L., Lluesma Gomez, M., Angla Navarro, A., Garcia‐Heredia, I., Martinez‐Hernandez, F., & Martinez‐Garcia, M. (2019). Insights into the antibiotic resistance dissemination in a wastewater effluent microbiome: Bacteria, viruses and vesicles matter. Environmental Microbiology, 21(12), 4582–4596. https://doi.org/10.1111/1462‐2920.14758
Manning, A. J., & Kuehn, M. J. (2011). Contribution of bacterial outer membrane vesicles to innate bacterial defense. BMC Microbiology, 11, 258. https://doi.org/10.1186/1471‐2180‐11‐258
Mashburn, L. M., & Whiteley, M. (2005). Membrane vesicles traffic signals and facilitate group activities in a prokaryote. Nature, 437(7057), 422–425. https://doi.org/10.1038/nature03925
McMillan, H. M., & Kuehn, M. J. (2023). Proteomic profiling reveals distinct bacterial extracellular vesicle subpopulations with possibly unique functionality. Applied and Environmental Microbiology, 89(1), e0168622. https://doi.org/10.1128/aem.01686‐22
Michalopoulos, A., & Falagas, M. E. (2008). Colistin and polymyxin B in critical care. Critical Care Clinics, 24(2), 377–391. x. https://doi.org/10.1016/j.ccc.2007.12.003
Olaya‐Abril, A., Prados‐Rosales, R., McConnell, M. J., Martín‐Peña, R., González‐Reyes, J. A., Jiménez‐Munguía, I., Gómez‐Gascón, L., Fernández, J., Luque‐García, J. L., García‐Lidón, C., Estévez, H., Pachón, J., Obando, I., Casadevall, A., Pirofski, L. A., & Rodríguez‐Ortega, M. J. (2014). Characterization of protective extracellular membrane‐derived vesicles produced by Streptococcus pneumoniae. Journal of Proteomics, 106, 46–60. https://doi.org/10.1016/j.jprot.2014.04.023
Paczosa, M. K., & Mecsas, J. (2016). Klebsiella pneumoniae: Going on the offense with a strong defense. Microbiology and Molecular Biology Reviews: MMBR, 80(3), 629–661. https://doi.org/10.1128/MMBR.00078‐15
Park, J., Kim, M., Shin, B., Kang, M., Yang, J., Lee, T. K., & Park, W. (2021). A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii. Elife, 10, e66988. https://doi.org/10.7554/eLife.66988
Preuß, E. B., Schubert, S., Werlein, C., Stark, H., Braubach, P., Höfer, A., Plucinski, E. K. J., Shah, H. R., Geffers, R., Sewald, K., Braun, A., Jonigk, D. D., & Kühnel, M. P. (2022). The challenge of long‐term cultivation of human precision‐cut lung slices. The American Journal of Pathology, 192(2), 239–253. https://doi.org/10.1016/j.ajpath.2021.10.020
Rafiee, R., Eftekhar, F., & Tabatabaii, S. A. (2017). Extended‐spectrum beta‐lactamases in cystic fibrosis isolates of Klebsiella pneumoniae. Jundishapur Journal of Microbiology, 11(1), e61086. https://doi.org/10.5812/jjm.61086
Riwu, K. H. P., Effendi, M. H., Rantam, F. A., Khairullah, A. R., & Widodo, A. (2022). A review: Virulence factors of Klebsiella pneumonia as emerging infection on the food chain. Veterinary World, 15(9), 2172–2179. https://doi.org/10.14202/vetworld.2022.2172‐2179
Roszkowiak, J., Jajor, P., Guła, G., Gubernator, J., Żak, A., Drulis‐Kawa, Z., & Augustyniak, D. (2019). Interspecies outer membrane vesicles (OMVs) modulate the sensitivity of pathogenic bacteria and pathogenic yeasts to cationic peptides and serum complement. International Journal of Molecular Sciences, 20(22), 5577. https://doi.org/10.3390/ijms20225577
Russo, T. A., & Marr, C. M. (2019). Hypervirulent Klebsiella pneumoniae. Clinical Microbiology Reviews, 32(3), e00001–e00019. https://doi.org/10.1128/CMR.00001‐19
Schroll, C., Barken, K. B., Krogfelt, K. A., & Struve, C. (2010). Role of type 1 and type 3 fimbriae in Klebsiella pneumoniae biofilm formation. BMC Microbiology, 10, 179. https://doi.org/10.1186/1471‐2180‐10‐179
Schwechheimer, C., & Kuehn, M. J. (2015). Outer‐membrane vesicles from Gram‐negative bacteria: Biogenesis and functions. Nature Reviews Microbiology, 13(10), 605–619. https://doi.org/10.1038/nrmicro3525
Tran, T. B., Velkov, T., Nation, R. L., Forrest, A., Tsuji, B. T., Bergen, P. J., & Li, J. (2016). Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: Are we there yet? International Journal of Antimicrobial Agents, 48(6), 592–597. https://doi.org/10.1016/j.ijantimicag.2016.09.010
Uhl, F. E., Vierkotten, S., Wagner, D. E., Burgstaller, G., Costa, R., Koch, I., Lindner, M., Meiners, S., Eickelberg, O., & Königshoff, M. (2015). Preclinical validation and imaging of Wnt‐induced repair in human 3D lung tissue cultures. The European Respiratory Journal, 46(4), 1150–1166. https://doi.org/10.1183/09031936.00183214
Welsh, J. A., Goberdhan, D. C. I., O'Driscoll, L., Buzas, E. I., Blenkiron, C., Bussolati, B., Cai, H., Di Vizio, D., Driedonks, T. A. P., Erdbrügger, U., Falcon‐Perez, J. M., Fu, Q. L., Hill, A. F., Lenassi, M., Lim, S. K., Mahoney, M. G., Mohanty, S., Möller, A., Nieuwland, R., … Witwer, K. W. (2024). Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. Journal of Extracellular Vesicles, 13(2), e12404. https://doi.org/10.1002/jev2.12404
World Health Organization. (2017). WHO publishes list of bacteria for which new antibiotics are urgently needed. Geneva. Online verfügbar unter https://www.who.int/news/item/27‐02‐2017‐who‐publishes‐list‐of‐bacteria‐for‐which‐new‐antibiotics‐are‐urgently‐needed, zuletzt geprüft am 21.06.2023
Yun, S. H., Park, E. C., Lee, S. Y., Lee, H., Choi, C. W., Yi, Y. S., Ro, H. J., Lee, J. C., Jun, S., Kim, H. Y., Kim, G. H., & Kim, S. I. (2018). Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug‐resistant clinical strain, Acinetobacter baumannii DU202. Clinical Proteomics, 15, 28. https://doi.org/10.1186/s12014‐018‐9204‐2
Zavan, L., Fang, H., Johnston, E. L., Whitchurch, C., Greening, D. W., Hill, A. F., & Kaparakis‐Liaskos, M. (2023). The mechanism of Pseudomonas aeruginosa outer membrane vesicle biogenesis determines their protein composition. Proteomics, 23(10), e2200464. https://doi.org/10.1002/pmic.202200464
Zhang, X., Qian, C., Tang, M., Zeng, W., Kong, J., Fu, C., Xu, C., Ye, J., & Zhou, T. (2023). Carbapenemase‐loaded outer membrane vesicles protect Pseudomonas aeruginosa by degrading imipenem and promoting mutation of antimicrobial resistance gene. Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy, 68, 100952. https://doi.org/10.1016/j.drup.2023.100952
Zhao, Z., Wang, L., Miao, J., Zhang, Z., Ruan, J., Xu, L., Guo, H., Zhang, M., & Qiao, W. (2022). Regulation of the formation and structure of biofilms by quorum sensing signal molecules packaged in outer membrane vesicles. The Science of the Total Environment, 806(Pt 4), 151403. https://doi.org/10.1016/j.scitotenv.2021.151403
Zingl, F. G., Kohl, P., Cakar, F., Leitner, D. R., Mitterer, F., Bonnington, K. E., Rechberger, G. N., Kuehn, M. J., Guan, Z., Reidl, J., & Schild, S. (2020). Outer membrane vesiculation facilitates surface exchange and in vivo adaptation of Vibrio cholerae. Cell Host & Microbe, 27(2), 225–237.e8. https://doi.org/10.1016/j.chom.2019.12.002