Pseudomonas aeruginosa breaches respiratory epithelia through goblet cell invasion in a microtissue model.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
10 Jun 2024
10 Jun 2024
Historique:
received:
15
06
2023
accepted:
29
04
2024
medline:
11
6
2024
pubmed:
11
6
2024
entrez:
10
6
2024
Statut:
aheadofprint
Résumé
Pseudomonas aeruginosa, a leading cause of severe hospital-acquired pneumonia, causes infections with up to 50% mortality rates in mechanically ventilated patients. Despite some knowledge of virulence factors involved, it remains unclear how P. aeruginosa disseminates on mucosal surfaces and invades the tissue barrier. Using infection of human respiratory epithelium organoids, here we observed that P. aeruginosa colonization of apical surfaces is promoted by cyclic di-GMP-dependent asymmetric division. Infection with mutant strains revealed that Type 6 Secretion System activities promote preferential invasion of goblet cells. Type 3 Secretion System activity by intracellular bacteria induced goblet cell death and expulsion, leading to epithelial rupture which increased bacterial translocation and dissemination to the basolateral epithelium. These findings show that under physiological conditions, P. aeruginosa uses coordinated activity of a specific combination of virulence factors and behaviours to invade goblet cells and breach the epithelial barrier from within, revealing mechanistic insight into lung infection dynamics.
Identifiants
pubmed: 38858595
doi: 10.1038/s41564-024-01718-6
pii: 10.1038/s41564-024-01718-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Parker, D. & Prince, A. Innate immunity in the respiratory epithelium. Am. J. Respir. Cell Mol. Biol. 45, 189–201 (2011).
pubmed: 21330463
pmcid: 3175551
doi: 10.1165/rcmb.2011-0011RT
Tsang, K. et al. Interaction of Pseudomonas aeruginosa with human respiratory mucosa in vitro. Eur. Respir. J. 7, 1746–1753 (1994).
Schwarzer, C., Fischer, H. & Machen, T. E. Chemotaxis and binding of Pseudomonas aeruginosa to scratch-wounded human cystic fibrosis airway epithelial cells. PLoS ONE 11, e0150109 (2016).
pubmed: 27031335
pmcid: 4816407
doi: 10.1371/journal.pone.0150109
Happel, K. I., Nelson, S. & Summer, W. The lung in sepsis: fueling the fire. Am. J. Med. Sci. 328, 230–237 (2004).
pubmed: 15486538
doi: 10.1097/00000441-200410000-00006
Giantsou, E. & Manolas, K. I. Superinfections in Pseudomonas aeruginosa ventilator-associated pneumonia. Minerva Anestesiol. 77, 964–970 (2011).
pubmed: 21952596
Tramper‐Stranders, G. A. et al. Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis: characteristics of eradicated and persistent isolates. Clin. Microbiol. Infect. 18, 567–574 (2012).
pubmed: 21883670
doi: 10.1111/j.1469-0691.2011.03627.x
Bustamante-Marin, X. M. & Ostrowski, L. E. Cilia and mucociliary clearance. Cold Spring Harb. Perspect. Biol. 9, a028241 (2017).
doi: 10.1101/cshperspect.a028241
Carvajal, L. A. & Pérez, C. P. Epidemiology of Respiratory Infections. in Pediatric Respiratory Diseases: A Comprehensive Textbook (eds Bertrand, P. & Sánchez, I.) 263–272 (Springer, 2020).
Hiemstra, P. S., McCray, P. B. & Bals, R. The innate immune function of airway epithelial cells in inflammatory lung disease. Eur. Respir. J. 45, 1150–1162 (2015).
pubmed: 25700381
pmcid: 4719567
doi: 10.1183/09031936.00141514
Almagro, P. et al. Pseudomonas aeruginosa and mortality after hospital admission for chronic obstructive pulmonary disease. Respiration 84, 36–43 (2012).
pubmed: 21996555
doi: 10.1159/000331224
Gellatly, S. L. & Hancock, R. E. W. Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. Pathog. Dis. 67, 159–173 (2013).
pubmed: 23620179
doi: 10.1111/2049-632X.12033
Engel, J. & Balachandran, P. Role of Pseudomonas aeruginosa type III effectors in disease. Curr. Opin. Microbiol. 12, 61–66 (2009).
pubmed: 19168385
doi: 10.1016/j.mib.2008.12.007
Heiniger, R. W., Winther-Larsen, H. C., Pickles, R. J., Koomey, M. & Wolfgang, M. C. Infection of human mucosal tissue by Pseudomonas aeruginosa requires sequential and mutually dependent virulence factors and a novel pilus-associated adhesin. Cell. Microbiol. 12, 1158–1173 (2010).
pubmed: 20331639
pmcid: 2906647
doi: 10.1111/j.1462-5822.2010.01461.x
Bucior, I., Mostov, K. & Engel, J. N. Pseudomonas aeruginosa-mediated damage requires distinct receptors at the apical and basolateral surfaces of the polarized epithelium. Infect. Immun. 78, 939–953 (2010).
pubmed: 20008530
doi: 10.1128/IAI.01215-09
Fleiszig, S. M. et al. Epithelial cell polarity affects susceptibility to Pseudomonas aeruginosa invasion and cytotoxicity. Infect. Immun. 65, 2861–2867 (1997).
pubmed: 9199460
pmcid: 175402
doi: 10.1128/iai.65.7.2861-2867.1997
Engel, J. & Eran, Y. Subversion of mucosal barrier polarity by Pseudomonas aeruginosa. Front. Microbiol. 2, 114 (2011).
pubmed: 21747810
pmcid: 3129012
doi: 10.3389/fmicb.2011.00114
Kazmierczak, B. I., Mostov, K. & Engel, J. N. Epithelial cell polarity alters rho-GTPase responses to Pseudomonas aeruginosa. Mol. Biol. Cell 15, 411–419 (2004).
pubmed: 14595106
pmcid: 329196
doi: 10.1091/mbc.e03-08-0559
Golovkine, G. et al. Pseudomonas aeruginosa transmigrates at epithelial cell-cell junctions, exploiting sites of cell division and senescent cell extrusion. PLoS Pathog. 12, e1005377 (2016).
pubmed: 26727615
pmcid: 4699652
doi: 10.1371/journal.ppat.1005377
Kierbel, A. et al. Pseudomonas aeruginosa exploits a PIP3-dependent pathway to transform apical into basolateral membrane. J. Cell Biol. 177, 21–27 (2007).
pubmed: 17403925
pmcid: 2064102
doi: 10.1083/jcb.200605142
Kierbel, A., Gassama-Diagne, A., Mostov, K. & Engel, J. N. The phosphoinositol-3-kinase–protein kinase B/Akt pathway is critical for Pseudomonas aeruginosa strain PAK internalization. Mol. Biol. Cell 16, 2577–2585 (2005).
pubmed: 15772151
pmcid: 1087259
doi: 10.1091/mbc.e04-08-0717
Plotkowski, M. C. et al. Pseudomonas aeruginosa internalization by human epithelial respiratory cells depends on cell differentiation, polarity, and junctional complex integrity. Am. J. Respir. Cell Mol. Biol. 20, 880–890 (1999).
pubmed: 10226058
doi: 10.1165/ajrcmb.20.5.3408
Lopes, S. F. et al. Primary and immortalized human respiratory cells display different patterns of cytotoxicity and cytokine release upon exposure to deoxynivalenol, nivalenol and fusarenon-X. Toxins 9, 337 (2017).
doi: 10.3390/toxins9110337
Barron, S. L., Saez, J. & Owens, R. M. In vitro models for studying respiratory host–pathogen interactions. Adv. Biol. 5, 2000624 (2021).
Seok, J. et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc. Natl Acad. Sci. USA 110, 3507–3512 (2013).
pubmed: 23401516
pmcid: 3587220
doi: 10.1073/pnas.1222878110
Worp et al. Can animal models of disease reliably inform human studies? PLoS Med. 7, e1000245 (2010).
pubmed: 20361020
pmcid: 2846855
doi: 10.1371/journal.pmed.1000245
Uhl, E. W. & Warner, N. J. Mouse models as predictors of human responses: evolutionary medicine. Curr. Pathobiol. Rep. 3, 219–223 (2015).
pubmed: 26246962
pmcid: 4522464
doi: 10.1007/s40139-015-0086-y
Chia, S. P. S., Kong, S. L. Y., Pang, J. K. S. & Soh, B.-S. 3D human organoids: the next “viral” model for the molecular basis of infectious diseases. Biomedicines 10, 1541 (2022).
pubmed: 35884846
pmcid: 9312734
doi: 10.3390/biomedicines10071541
Sato, T. et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141, 1762–1772 (2011).
pubmed: 21889923
doi: 10.1053/j.gastro.2011.07.050
Rock, J. R. et al. Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc. Natl Acad. Sci. USA 106, 12771–12775 (2009).
pubmed: 19625615
pmcid: 2714281
doi: 10.1073/pnas.0906850106
Youk, J. et al. Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2. Cell Stem Cell 27, 905–919.e10 (2020).
pubmed: 33142113
pmcid: 7577700
doi: 10.1016/j.stem.2020.10.004
Schwank, G. et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13, 653–658 (2013).
pubmed: 24315439
doi: 10.1016/j.stem.2013.11.002
Sachs, N. et al. Long‐term expanding human airway organoids for disease modeling. EMBO J. 38, e100300 (2019).
pubmed: 30643021
pmcid: 6376275
doi: 10.15252/embj.2018100300
Han, Y. et al. Identification of SARS-CoV-2 inhibitors using lung and colonic organoids. Nature 589, 270–275 (2021).
pubmed: 33116299
doi: 10.1038/s41586-020-2901-9
Heo, I. et al. Modelling Cryptosporidium infection in human small intestinal and lung organoids. Nat. Microbiol. 3, 814–823 (2018).
pubmed: 29946163
pmcid: 6027984
doi: 10.1038/s41564-018-0177-8
García, S. R. et al. Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures. Development 146, dev.177428 (2019).
doi: 10.1242/dev.177428
Ozer, E. A., Nnah, E., Didelot, X., Whitaker, R. J. & Hauser, A. R. The population structure of Pseudomonas aeruginosa is characterized by genetic isolation of exoU+ and exoS+ lineages. Genome Biol. Evol. 11, 1780–1796 (2019).
pubmed: 31173069
pmcid: 6690169
doi: 10.1093/gbe/evz119
Fahy, J. V. & Dickey, B. F. Airway mucus function and dysfunction. N. Engl. J. Med. 363, 2233–2247 (2010).
pubmed: 21121836
pmcid: 4048736
doi: 10.1056/NEJMra0910061
Liao, C., Huang, X., Wang, Q., Yao, D. & Lu, W. Virulence factors of Pseudomonas aeruginosa and antivirulence strategies to combat its drug resistance. Front. Cell Infect. Microbiol. 12, 926758 (2022).
pubmed: 35873152
pmcid: 9299443
doi: 10.3389/fcimb.2022.926758
Williams, P. & Cámara, M. Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr. Opin. Microbiol. 12, 182–191 (2009).
pubmed: 19249239
doi: 10.1016/j.mib.2009.01.005
Jimenez, P. N. et al. The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol. Mol. Biol. Rev. 76, 46–65 (2012).
pubmed: 22390972
doi: 10.1128/MMBR.05007-11
Persat, A., Inclán, Y. F., Engel, J. N., Stone, H. A. & Gitai, Z. Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 112, 7563–7568 (2015).
pubmed: 26041805
pmcid: 4475988
doi: 10.1073/pnas.1502025112
Klockgether, J. & Tümmler, B. Recent advances in understanding Pseudomonas aeruginosa as a pathogen. F1000Research 6, 1261 (2017).
pubmed: 28794863
pmcid: 5538032
doi: 10.12688/f1000research.10506.1
Bleves, S. et al. Protein secretion systems in Pseudomonas aeruginosa: a wealth of pathogenic weapons. Int. J. Med. Microbiol. 300, 534–543 (2010).
pubmed: 20947426
doi: 10.1016/j.ijmm.2010.08.005
O’Toole, G. A. & Kolter, R. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol. Microbiol. 30, 295–304 (1998).
pubmed: 9791175
doi: 10.1046/j.1365-2958.1998.01062.x
Giltner, C. L., Nguyen, Y. & Burrows, L. L. Type IV pilin proteins: versatile molecular modules. Microbiol. Mol. Biol. Rev. 76, 740–772 (2012).
pubmed: 23204365
pmcid: 3510520
doi: 10.1128/MMBR.00035-12
Laventie, B.-J. et al. A surface-induced asymmetric program promotes tissue colonization by Pseudomonas aeruginosa. Cell Host Microbe 25, 140–152.e6 (2019).
pubmed: 30581112
doi: 10.1016/j.chom.2018.11.008
Luo, Y. et al. A hierarchical cascade of second messengers regulates Pseudomonas aeruginosa surface behaviors. mBio 6, e02456-14 (2015).
pubmed: 25626906
pmcid: 4324313
doi: 10.1128/mBio.02456-14
Kazmierczak, B. I., Schniederberend, M. & Jain, R. Cross-regulation of Pseudomonas motility systems: the intimate relationship between flagella, pili and virulence. Curr. Opin. Microbiol. 28, 78–82 (2015).
pubmed: 26476804
pmcid: 4688086
doi: 10.1016/j.mib.2015.07.017
Valentini, M. & Filloux, A. Multiple roles of c-di-GMP signaling in bacterial pathogenesis. Annu. Rev. Microbiol. 73, 387–406 (2019).
pubmed: 31500536
doi: 10.1146/annurev-micro-020518-115555
Laventie, B.-J. & Jenal, U. Surface sensing and adaptation in bacteria. Annu. Rev. Microbiol. 74, 735–760 (2020).
pubmed: 32905753
doi: 10.1146/annurev-micro-012120-063427
Palmer, K. L., Aye, L. M. & Whiteley, M. Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum. J. Bacteriol. 189, 8079–8087 (2007).
pubmed: 17873029
pmcid: 2168676
doi: 10.1128/JB.01138-07
Kuek, L. E. & Lee, R. J. First contact: the role of respiratory cilia in host–pathogen interactions in the airways. Am. J. Physiol. Lung Cell Mol. Physiol. 319, L603–L619 (2020).
pubmed: 32783615
pmcid: 7516383
doi: 10.1152/ajplung.00283.2020
Widdicombe, J. H. & Wine, J. J. Airway gland structure and function. Physiol. Rev. 95, 1241–1319 (2015).
pubmed: 26336032
doi: 10.1152/physrev.00039.2014
Sana, T. G. et al. Internalization of Pseudomonas aeruginosa strain PAO1 into epithelial cells is promoted by interaction of a T6SS effector with the microtubule network. mBio 6, e00712-15 (2015).
pubmed: 26037124
pmcid: 4453011
doi: 10.1128/mBio.00712-15
Sana, T. G. et al. The second type VI secretion system of Pseudomonas aeruginosa strain PAO1 is regulated by quorum sensing and fur and modulates internalization in epithelial cells. J. Biol. Chem. 287, 27095–27105 (2012).
pubmed: 22665491
pmcid: 3411052
doi: 10.1074/jbc.M112.376368
Hogan, B. L. M. et al. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell 15, 123–138 (2014).
pubmed: 25105578
pmcid: 4212493
doi: 10.1016/j.stem.2014.07.012
Rossy, T. et al. Pseudomonas aeruginosa type IV pili actively induce mucus contraction to form biofilms in tissue-engineered human airways. PLoS Biol. 21, e3002209 (2023).
pubmed: 37527210
pmcid: 10393179
doi: 10.1371/journal.pbio.3002209
McDole, J. R. et al. Goblet cells deliver luminal antigen to CD103
pubmed: 22422267
pmcid: 3313460
doi: 10.1038/nature10863
Jiang, F., Waterfield, N. R., Yang, J., Yang, G. & Jin, Q. A Pseudomonas aeruginosa type VI secretion phospholipase D effector targets both prokaryotic and eukaryotic cells. Cell Host Microbe 15, 600–610 (2014).
pubmed: 24832454
doi: 10.1016/j.chom.2014.04.010
Rajan, S. et al. Pseudomonas aeruginosa induction of apoptosis in respiratory epithelial cells. Am. J. Respir. Cell Mol. Biol. 23, 304–312 (2000).
pubmed: 10970820
doi: 10.1165/ajrcmb.23.3.4098
Yamaguchi, T. & Yamada, H. Role of mechanical injury on airway surface in the pathogenesis of Pseudomonas aeruginosa. Am. Rev. Respir. Dis. 144, 1147–1152 (1991).
pubmed: 1952446
doi: 10.1164/ajrccm/144.5.1147
Kumar, N. G. et al. Pseudomonas aeruginosa can diversify after host cell invasion to establish multiple intracellular niches. mBio 13, e02742-22 (2022).
pubmed: 36374039
pmcid: 9765609
doi: 10.1128/mbio.02742-22
Chastre, J. et al. Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial. Crit. Care 26, 355 (2022).
pubmed: 36380312
pmcid: 9666938
doi: 10.1186/s13054-022-04204-9
Hotinger, J. A. & May, A. E. Antibodies inhibiting the type III secretion system of Gram-negative pathogenic bacteria. Antibodies 9, 35 (2020).
pubmed: 32726928
pmcid: 7551047
doi: 10.3390/antib9030035
Jain, M. et al. Type III secretion phenotypes of Pseudomonas aeruginosa strains change during infection of individuals with cystic fibrosis. J. Clin. Microbiol. 42, 5229–5237 (2004).
pubmed: 15528719
pmcid: 525189
doi: 10.1128/JCM.42.11.5229-5237.2004
Huus, K. E. et al. Clinical isolates of Pseudomonas aeruginosa from chronically infected cystic fibrosis patients fail to activate the inflammasome during both stable infection and pulmonary exacerbation. J. Immunol. 196, 3097–3108 (2016).
pubmed: 26895832
doi: 10.4049/jimmunol.1501642
Rossi, E. et al. Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis. Nat. Rev. Microbiol. 19, 331–342 (2020).
pubmed: 33214718
doi: 10.1038/s41579-020-00477-5
Osan, J. et al. Goblet cell hyperplasia increases SARS-CoV-2 infection in chronic obstructive pulmonary disease. Microbiol. Spectr. 10, e00459-22 (2022).
pubmed: 35862971
pmcid: 9430117
doi: 10.1128/spectrum.00459-22
Adam, D. et al. Cystic fibrosis airway epithelium remodelling: involvement of inflammation. J. Pathol. 235, 408–419 (2015).
pubmed: 25348090
doi: 10.1002/path.4471
Jeffery, P. K. Comparison of the structural and inflammatory features of COPD and asthma. Giles F. Filley Lecture. Chest 117, 251S–260S (2000).
pubmed: 10843939
doi: 10.1378/chest.117.5_suppl_1.251S
Dovey, M. et al. Ultrastructural morphology of the lung in cystic fibrosis. J. Submicrosc. Cytol. Pathol. 21, 521–534 (1989).
pubmed: 2790733
Jeffery, P. K. Remodeling and inflammation of bronchi in asthma and chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc. 1, 176–183 (2004).
pubmed: 16113432
doi: 10.1513/pats.200402-009MS
Ravindra, N. G. et al. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLoS Biol. 19, e3001143 (2021).
pubmed: 33730024
pmcid: 8007021
doi: 10.1371/journal.pbio.3001143
Lukassen, S. et al. SARS‐CoV‐2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 39, e105114 (2020).
pubmed: 32246845
pmcid: 7232010
doi: 10.15252/embj.20105114
Ackermann, M. et al. Self-destructive cooperation mediated by phenotypic noise. Nature 454, 987–990 (2008).
pubmed: 18719588
doi: 10.1038/nature07067
Diard, M. et al. Stabilization of cooperative virulence by the expression of an avirulent phenotype. Nature 494, 353–356 (2013).
pubmed: 23426324
doi: 10.1038/nature11913
Kotte, O., Volkmer, B., Radzikowski, J. L. & Heinemann, M. Phenotypic bistability in Escherichia coli’s central carbon metabolism. Mol. Syst. Biol. 10, 736 (2014).
pubmed: 24987115
pmcid: 4299493
doi: 10.15252/msb.20135022
Basan, M. et al. A universal trade-off between growth and lag in fluctuating environments. Nature 584, 470–474 (2020).
pubmed: 32669712
pmcid: 7442741
doi: 10.1038/s41586-020-2505-4
Bakshi, S. et al. Tracking bacterial lineages in complex and dynamic environments with applications for growth control and persistence. Nat. Microbiol. 6, 783–791 (2021).
pubmed: 34017106
pmcid: 10277933
doi: 10.1038/s41564-021-00900-4
Balaban, N. Q., Merrin, J., Chait, R., Kowalik, L. & Leibler, S. Bacterial persistence as a phenotypic switch. Science 305, 1622–1625 (2004).
pubmed: 15308767
doi: 10.1126/science.1099390
Arnoldini, M. et al. Bistable expression of virulence genes in Salmonella leads to the formation of an antibiotic-tolerant subpopulation. PLoS Biol. 12, e1001928 (2014).
pubmed: 25136970
pmcid: 4138020
doi: 10.1371/journal.pbio.1001928
Manina, G., Griego, A., Singh, L. K., McKinney, J. D. & Dhar, N. Preexisting variation in DNA damage response predicts the fate of single mycobacteria under stress. EMBO J. 38, e101876 (2019).
pubmed: 31583725
pmcid: 6856624
doi: 10.15252/embj.2019101876
Keilberg, D., Zavros, Y., Shepherd, B., Salama, N. R. & Ottemann, K. M. Spatial and temporal shifts in bacterial biogeography and gland occupation during the development of a chronic infection. mBio 7, e01705-16 (2016).
pubmed: 27729513
pmcid: 5061875
doi: 10.1128/mBio.01705-16
Fung, C. et al. High-resolution mapping reveals that microniches in the gastric glands control Helicobacter pylori colonization of the stomach. PLoS Biol. 17, e3000231 (2019).
pubmed: 31048876
pmcid: 6497225
doi: 10.1371/journal.pbio.3000231
Garvis, S. et al. Caenorhabditis elegans semi-automated liquid screen reveals a specialized role for the chemotaxis gene cheB2 in Pseudomonas aeruginosa virulence. PLoS Pathog. 5, e1000540 (2009).
pubmed: 19662168
pmcid: 2714965
doi: 10.1371/journal.ppat.1000540
Laganenka, L. et al. Chemotaxis and autoinducer-2 signalling mediate colonization and contribute to co-existence of Escherichia coli strains in the murine gut. Nat. Microbiol. 8, 204–217 (2023).
pubmed: 36624229
doi: 10.1038/s41564-022-01286-7
Cooper, K. G. et al. Regulatory protein HilD stimulates Salmonella Typhimurium invasiveness by promoting smooth swimming via the methyl-accepting chemotaxis protein McpC. Nat. Commun. 12, 348 (2021).
pubmed: 33441540
pmcid: 7806825
doi: 10.1038/s41467-020-20558-6
Lane, M. C. et al. Role of motility in the colonization of uropathogenic Escherichia coli in the urinary tract. Infect. Immun. 73, 7644–7656 (2005).
pubmed: 16239569
pmcid: 1273871
doi: 10.1128/IAI.73.11.7644-7656.2005
Broder, U. N., Jaeger, T. & Jenal, U. LadS is a calcium-responsive kinase that induces acute-to-chronic virulence switch in Pseudomonas aeruginosa. Nat. Microbiol. 2, 16184 (2016).
pubmed: 27775685
doi: 10.1038/nmicrobiol.2016.184
Haubold, B., Klötzl, F. & Pfaffelhuber, P. andi: fast and accurate estimation of evolutionary distances between closely related genomes. Bioinformatics 31, 1169–1175 (2015).
pubmed: 25504847
doi: 10.1093/bioinformatics/btu815
Letunic, I. & Bork, P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 49, W293–W296 (2021).
pubmed: 33885785
pmcid: 8265157
doi: 10.1093/nar/gkab301
Emms, D. M. & Kelly, S. OrthoFinder: phylogenetic orthology inference for comparative genomics. Genome Biol. 20, 238 (2019).
pubmed: 31727128
pmcid: 6857279
doi: 10.1186/s13059-019-1832-y
Swart, A. L. Pseudomonas aeruginosa breaches respiratory epithelia through goblet cell invasion in a microtissue model. BioImage Archive https://doi.org/10.6019/S-BIAD1083 (2024).
Swart, A. L. & Laventie, B.-J. Pseudomonas aeruginosa breaches respiratory epithelia through goblet cell invasion in a microtissue model. Zenodo https://doi.org/10.5281/zenodo.10650981 (2024).