Pseudomonas aeruginosa -Catecholamine Inotrope Interactions
Abstract
Background Ventilated patients receiving intensive care are at significant risk of acquiring a ventilator-associated pneumonia that is associated with significant morbidity and mortality. Despite intensive research, it is still unclear why Pseudomonas aeruginosa, a microbe that rarely causes pneumonia outside of intensive care, is responsible for so many of these infections.Methods We investigated whether medications frequently prescribed to patients in the ICU, the catecholamine inotropes, were affecting the growth and virulence of P aeruginosa . Effects of clinically attainable concentrations of inotropes on P aeruginosa pathogenicity were explored using in vitro growth and virulence assays and an ex vivo model of infection using ciliated human respiratory epithelium.Results We found that inotropes were potent stimulators of P aeruginosa growth, producing upto 50-fold increases in bacterial numbers via a mechanism involving inotrope delivery of transferrin-ron,internalization of the inotrope, and upregulation of the key pseudomonal siderophore pyoverdine.Inotropes also markedly increased biofilm formation on endotracheal tubing and enhanced the biofilm production and toxicity of P aeruginosa in its interaction with respiratory epithelium.Importantly, catecholamine inotropes also facilitated the rapid recovery of P aeruginosa from tobramycin antibiotic challenge. We also tested out the effect of the inotropes vasopressin and phenylephrine on the growth and virulence of P aeruginosa and found that, in contrast to the catecholamines,these drugs had no stimulatory effect.Conclusions Collectively, our results suggest that catecholamine inotrope-bacterial interactions may be an unexpected contributory factor to the development of P aeruginosa -ventilator-associated pneumonia.
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Catecholamines can behave as siderophores, causing release of iron from host-iron sequestering proteins, increasing iron availability for bacteria and enhancing bacterial growth.
“Second, catecholamines can behave as siderophores, which cause the release of iron from host-iron sequestering proteins, increasing the availability of iron for bacteria, thereby enhancing bacterial growth (Freestone et al., 2012).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Freestone et al., 2012
In acute illness, the normally nutrient-poor alveolus is flooded with nutrient-rich oedema, oxygen and temperature gradients are established, and host stress signalling molecules selectively promote the growth of potential pathogens.
“The normally nutrient-poor environment of the alveolus is flooded with nutrient-rich oedema,55 pockets of oxygen and heterogeneous temperature gradients are established,48,49 and the signalling molecules of the host stress response selectively promote the growth of potential pathogens.”
From The microbiome and critical illness (2016) · cites this paper as [51]
Many daily therapies and interventions in intensive care increase intestinal permeability, bacterial translocation, and bacterial virulence.
“Many daily therapies and interventions in intensive care increase intestinal permeability (eg, nonsteroidal anti-inflammatory drugs109 and parenteral feeding55,82), bacterial translocation (eg, antibiotics,65 corticosteroids,110 and opiates111), and bacterial virulence (eg, opiates19 and catecholamines22,51).”
From The microbiome and critical illness (2016) · cites this paper as [51]
In vitro, the growth of P aeruginosa is increased by the presence of catecholamines.
“In vitro, the growth of P aeruginosa is increased by the presence of catecholamines”
From The microbiome and critical illness (2016) · cites this paper as [51]
Cites
Determination of minimum inhibitory concentrations
Andrews, J. M. (2001) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/48.suppl_1.5 · Cited by 4,129 · see citing works
Flagellar and twitching motility are necessary for <i>Pseudomonas aeruginosa</i> biofilm development
O'Toole, G. A., & Kolter, R. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.01062.x · Cited by 2,697 · see citing works
O'Toole, G. A., & Kolter, R. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.00797.x · Cited by 2,537 · see citing works
Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock
Russell, J. A., Walley, K. R., Singer, J., Gordon, A. C., Hébert, P. C., Cooper, D. J., Holmes, C. L., Mehta, S., Granton, J. T., Storms, M. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa067373 · Cited by 1,924 · see citing works
Iron Metabolism in Pathogenic Bacteria
Ratledge, C., & Dover, L. G. (2000) · Annual Review of Microbiology · doi:10.1146/annurev.micro.54.1.881 · Cited by 1,539 · see citing works
Vasopressin Deficiency Contributes to the Vasodilation of Septic Shock
Landry, D. W., Levin, H. R., Gallant, E. M., Ashton, R. C., Seo, S., D'Alessandro, D., Oz, M. C., & Oliver, J. A. (1997) · Circulation · doi:10.1161/01.cir.95.5.1122 · Cited by 990 · see citing works
Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock
Tsuneyoshi, I., Yamada, H., Kakihana, Y., et al. (2001) · Critical Care Medicine · doi:10.1097/00003246-200103000-00004 · Cited by 592 · see citing works
Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium
Mesaros, N. E., Nordmann, P., Plésiat, P., Roussel‐Delvallez, M., Eldere, J. V., Glupczynski, Y., Laethem, Y. V., Jacobs, F., Lebecque, P., Malfroot, A., et al. (2007) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2007.01681.x · Cited by 585 · see citing works
Lamont, I. L., Beare, P. A., Ochsner, U., Vasil, A. I., & Vasil, M. L. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092016999 · Cited by 584 · see citing works
Sources and Significance of Plasma Levels of Catechols and Their Metabolites in Humans
Goldstein, D. S., Eisenhofer, G., & Kopin, I. J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.049270 · Cited by 441 · see citing works
Catecholamine induced growth of gram negative bacteria
Lyte, M., & Ernst, S. (1992) · Life Sciences · doi:10.1016/0024-3205(92)90273-r · Cited by 396 · see citing works
Adonizio, A. L., Kong, K., & Mathee, K. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00612-07 · Cited by 375 · see citing works
Pseudomonas aeruginosa biofilm formation in the cystic fibrosis airway
Moreau‐Marquis, S., Stanton, B. A., & O’Toole, G. A. (2007) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2007.12.001 · Cited by 338 · see citing works
Microbial endocrinology: how stress influences susceptibility to infection
Freestone, P. P. E., Sandrini, S. M., Haigh, R. D., & Lyte, M. (2008) · Trends in Microbiology · doi:10.1016/j.tim.2007.11.005 · Cited by 299 · see citing works
Self-citationFreestone, P. P. E., WILLIAMS, P. H., Haigh, R., Maggs, A. F., Neal, C. P., & Lyte, M. (2002) · Shock · doi:10.1097/00024382-200211000-00014 · Cited by 227 · see citing works
Self-citationAlverdy, J., Holbrook, C., Rocha, F., Seiden, L., Licheng, R., Wu, Musch, M., Chang, E., Ohman, D., & Suh, S. (2000) · Annals of Surgery · doi:10.1097/00000658-200010000-00003 · Cited by 207 · see citing works
Stimulation of Staphylococcus epidermidis growth and biofilm formation by catecholamine inotropes
Lyte, M., Freestone, P. P. E., Neal, C. P., Olson, B. A., Haigh, R., Bayston, R., & WILLIAMS, P. H. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12231-3 · Cited by 205 · see citing works
Self-citationStimulation of bacterial growth by heat-stable, norepinephrine-induced autoinducers
Freestone, P. P. E., Haigh, R. D., Williams, P. H., & Lyte, M. (1999) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1999.tb13449.x · Cited by 199 · see citing works
Self-citationYang, L., Nilsson, M., Gjermansen, M., et al. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06934.x · Cited by 173 · see citing works
Pseudomonas aeruginosa pneumonia
Garau, J., & Gómez, L. (2003) · Current Opinion in Infectious Diseases · doi:10.1097/00001432-200304000-00010 · Cited by 166 · see citing works
Bailey, M. T., Engler, H., & Sheridan, J. F. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.09.008 · Cited by 133 · see citing works
Ventilator-Associated Pneumonia
Morehead, R. S., & Pinto, S. J. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.13.1926 · Cited by 119 · see citing works
Ciliated Air-Liquid Cultures as an Aid to Diagnostic Testing of Primary Ciliary Dyskinesia
Hirst, R. A., Rutman, A., Williams, G., et al. (2010) · CHEST Journal · doi:10.1378/chest.10-0175 · Cited by 107 · see citing works
Self-citationIron acquisition by Pseudomonas aeruginosa in the lungs of patients with cystic fibrosis
Lamont, I. L., Konings, A. F., & Reid, D. W. (2009) · BioMetals · doi:10.1007/s10534-008-9197-9 · Cited by 77 · see citing works
Dopamine clearance in critically ill patients
Juste, R. N., Moran, L. K., Hooper, J., et al. (1998) · Intensive Care Medicine · doi:10.1007/s001340050747 · Cited by 76 · see citing works
Contribution of endotracheal tubes to the pathogenesis of ventilator-associated pneumonia
Koerner, R. J. (1997) · Journal of Hospital Infection · doi:10.1016/s0195-6701(97)90096-7 · Cited by 70 · see citing works
Thompson, J. P., Boyle, J. R., THOMPSON, M. M., Strupish, J. W., BELL, P. R. F., & Smith, G. (1999) · European Journal of Vascular and Endovascular Surgery · doi:10.1053/ejvs.1998.0760 · Cited by 66 · see citing works
An exploratory analysis of medication utilization in a medical intensive care unit
Smythe, M. A., MELENDY, S., Jahns, B. E., et al. (1993) · Critical Care Medicine · doi:10.1097/00003246-199309000-00014 · Cited by 56 · see citing works
Prevention measures for ventilator-associated pneumonia: a new focus on the endotracheal tube
Ramírez, P., Ferrer, M., & Torres, A. (2007) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0b013e328014daac · Cited by 55 · see citing works
Raymondos, K., Panning, B., Leuwer, M., et al. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-132-10-200005160-00007 · Cited by 52 · see citing works
Shorr, A. F., Jackson, W. L., Weiss, B. M., & Moores, L. K. (2005) · CHEST Journal · doi:10.1378/chest.128.5_suppl_2.583s · Cited by 51 · see citing works
Freestone, P. P. E., Haigh, R., & Lyte, M. (2008) · The Journal of Infectious Diseases · doi:10.1086/529202 · Cited by 51 · see citing works
Self-citationSchmidt, C., & Kraft, K. (1996) · PubMed · Cited by 48 · see citing works
Ventilator-Associated Pneumonia
Shorr, A. F., & Kollef, M. H. (2005) · CHEST Journal · doi:10.1016/s0012-3692(15)31064-3 · Cited by 44 · see citing works
Girbes, A. R. J., Patten, M. T., McCloskey, B. V., et al. (2000) · Intensive Care Medicine · doi:10.1007/s001340000686 · Cited by 35 · see citing works
Augmentation of Endogenous Dopamine Production Increases Lung Liquid Clearance
Adir, Y., Azzam, Z. S., Lecuona, E., et al. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200207-744oc · Cited by 30 · see citing works
Lucero, M. T., & Squires, A. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00825-7 · Cited by 26 · see citing works
SHINDO, H., Nakajima, E., Kawai, K., et al. (1973) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.21.817 · Cited by 21 · see citing works
Analysis of phenylephrine in plasma: Initial data about the concentration-effect relationship
Martinsson, A., Beveg�rd, S., & Hjemdahl, P. (1986) · European Journal of Clinical Pharmacology · doi:10.1007/bf00607955 · Cited by 17 · see citing works
The effect of viscous loading on brain ependymal cilia
O’Callaghan, C., Sikand, K. S., Rutman, A., et al. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.04.095 · Cited by 17 · see citing works
Self-citationTargeted antibiotic management of ventilator-associated pneumonia
Fagon, J.-Y., & Rello, J. (2006) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2006.01652.x · Cited by 13 · see citing works
Stannard, W., & Callaghan, C. O. (2002) · Pediatric Drugs · doi:10.2165/00128072-200204040-00003 · Cited by 12 · see citing works
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
The Microbiome and the Respiratory Tract
Dickson, R. P., Erb-Downward, J. R., Martinez, F. J., & Huffnagle, G. B. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105238 · Cited by 953 · see citing works
The respiratory tract microbiome and lung inflammation: a two-way street.
Huffnagle, G. B., Dickson, R. P., & Lukacs, N. W. (2017) · Mucosal Immunology · doi:10.1038/mi.2016.108 · Cited by 535 · see citing works
The role of the microbiome in exacerbations of chronic lung diseases
Dickson, R. P., Martinez, F. J., & Huffnagle, G. B. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61136-3 · Cited by 495 · see citing works
The microbiome and critical illness
Dickson, R. P. (2016) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00427-0 · Cited by 460 · see citing works
Dickson, R. P., Erb-Downward, J. R., & Huffnagle, G. B. (2014) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(14)70028-1 · Cited by 371 · see citing works
Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans
Caza, M., & Kronstad, J. W. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00080 · Cited by 306 · see citing works
Microbial endocrinology: Host-bacteria communication within the gut microbiome
Sandrini, S., Aldriwesh, M., Alruways, M., & Freestone, P. (2015) · Journal of Endocrinology · doi:10.1530/joe-14-0615 · Cited by 130 · see citing works
Self-citationIntraalveolar catecholamines and the human lung microbiome
Dickson, R. P., Erb-Downward, J. R., Prescott, H. C., Martinez, F. J., Curtis, J. L., Lama, V. N., & Huffnagle, G. B. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201502-0326le · Cited by 59 · see citing works
Lyte, M., Villageliú, D. N., Crooker, B. A., & Brown, D. R. (2018) · Journal of Dairy Science · doi:10.3168/jds.2017-13589 · Cited by 38 · see citing works
- Authors
- Freestone, P. P., Hirst, R. A., Sandrini, S. M., Sharaff, F., Fry, H., Hyman, S., & O'Callaghan, C.
- Affiliations
- University of Leicester (GB)
- Venue
- Chest
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 142
- Issue
- 5
- Pages
- 1200-1210
- ISSN
- 0012-3692 (ISSN-L)
- OpenAlex
- W2122984467
- Cited by
- 107
- References
- 42
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 15 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 10 · 2019: 14 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 11 · 2014: 5 · 2013: 6 · 2012: 1
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CHEST Journal (publishedVersion)
- PubMed (publishedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Nosocomial Infections in ICU
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- Pseudomonas aeruginosa, ventilator-associated pneumonia, bacterial growth stimulation, pyoverdine, siderophores, biofilm formation, ciliated respiratory epithelium, vasopressin, phenylephrine, intensive care unit infections
- MeSH terms
- Analysis of Variance, Catecholamines, Humans, Microbial Sensitivity Tests, Pseudomonas aeruginosa, Pseudomonas Infections, Risk Factors, Virulence, Biofilms, Pneumonia, Ventilator-Associated
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