Gut-Derived Sepsis Occurs When the Right Pathogen With the Right Virulence Genes Meets the Right Host: Evidence for In Vivo Virulence Expression in Pseudomonas aeruginosa
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OBJECTIVE: To define the putative role of the PA-I lectin/adhesin, a binding protein of Pseudomonas aeruginosa, on lethal gut-derived sepsis after surgical stress, and to determine if this protein is expressed in vivo in response to physical and chemical changes in the local microenvironment of the intestinal tract after surgical stress. SUMMARY BACKGROUND DATA: Previous work from the authors' laboratory has established that lethal gut-derived sepsis can be induced after the introduction of P. aeruginosa into the cecum of mice after a 30% hepatectomy. This effect does not occur when P. aeruginosa is introduced into the cecum of sham operated control mice. Previous experiments further established that the mechanism of this effect is due to the presence of the PA-I lectin/adhesin of P. aeruginosa, which induces a permeability defect to a lethal cytotoxin of P. aeruginosa, exotoxin A. METHODS: Three strains of P. aeruginosa, one lacking functional PA-I, were tested in two complementary systems to assess virulence. Strains were tested for their ability to adhere to and alter the permeability of cultured human colon epithelial cells, and for their ability to induce mortality when injected into the cecum of mice after a 30% hepatectomy. To determine if PA-I is "in vivo expressed" when present in the cecal environment after hepatectomy, strains were retrieved from the cecum of sham-operated and hepatectomy-treated mice 24 and 48 hours after their introduction into the cecum and their PA-I expression was assessed. RESULTS: Results indicated that PA-I plays a putative role in lethal gut-derived sepsis in the mouse, because strains lacking functional PA-I had an attenuated effect on cultured human epithelial cells, and were nonlethal when injected into the cecum of mice after 30% surgical hepatectomy. Furthermore, surgical stress in the form of hepatectomy significantly altered the intestinal microenvironment, resulting in an increase in luminal norepinephrine associated with an increase in PA-I expression in retrieved strains of P. aeruginosa. Co-incubation of P. aeruginosa with norepinephrine increased PA-I expression in vitro, suggesting that norepinephrine plays a role in the observed response in vivo. CONCLUSIONS: Lethal gut-derived sepsis may occur when intestinal pathogens express virulence determinants in response to environmental signals indicating host stress. In this regard, the PA-I lectin/adhesin of P. aeruginosa appears to be a specific example of in vivo virulence expression in colonizing pathogens in the intestinal tract in response to surgical stress.
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Almost every common clinical intervention used in intensive care changes environmental growth conditions for intestinal bacteria.
“Almost every common clinical intervention used in intensive care (eg, enteral feeding,43 proton-pump inhibitors,38,39 systemic catecholamines,22,23 and systemic antibiotics65,66) changes environmental growth conditions for intestinal bacteria”
From The microbiome and critical illness (2016) · cites this paper as [22]
Translocation of microbes and microbial products is not necessary for the microbiome to cause systemic inflammation and injury.
“translocation of microbes and microbial products is not necessary for the microbiome to cause systemic inflammation and injury.”
From The microbiome and critical illness (2016) · cites this paper as [22]
The behaviour and virulence of individual gut community members are changed by the conditions of critical illness.
“the behaviour and virulence of individual community members are also changed.”
From The microbiome and critical illness (2016) · cites this paper as [22]
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 [22]
Norepinephrine release in the intestine during surgical trauma induces expression of virulent traits in Pseudomonas aeruginosa, which results in gut-derived sepsis.
“Norepinephrine release in the intestine during surgical trauma induces expression of virulent traits in Pseudomonas aeruginosa, which results in gut-derived sepsis.35”
From Principles and clinical implications of the brain-gut-enteric microbiota axis (2009) · cites this paper as [35]
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- Authors
- Alverdy, J., Holbrook, C., Rocha, F., Seiden, L., Licheng, R., Wu, Musch, M., Chang, E., Ohman, D., & Suh, S.
- Affiliations
- University of Chicago (US)
- Virginia Commonwealth University (US)
- Corresponding author
- Alverdy, John
- Holbrook, Christopher
- Rocha, Flavio
- Venue
- Annals of Surgery
- Published
- 2000-10
- Volume
- 232
- Issue
- 4
- Pages
- 480-489
- ISSN
- 0003-4932 (ISSN-L)
- PMC
- PMC1421180
- OpenAlex
- W2054867424
- Cited by
- 207
- References
- 30
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 18 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 7 · 2017: 7 · 2016: 11 · 2015: 15 · 2014: 10 · 2013: 4 · 2012: 12
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Surgery (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK047722, DK-47722, R37DK047722, R01DK038510, DK42086, DK38510, P30DK042086)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Nosocomial Infections in ICU
- Keywords
- gut-derived sepsis, Pseudomonas aeruginosa, surgical stress, hepatectomy, norepinephrine, intestinal microenvironment, exotoxin A, intestinal epithelial permeability, bacterial adhesion, cecum, host-pathogen interaction, sepsis prevention
- MeSH terms
- Animals, Bacterial Adhesion, Cecum, Genes, Bacterial, Hepatectomy, Humans, Mice, Inbred BALB C, Pseudomonas aeruginosa, Stress, Physiological, Virulence, Gene Expression Regulation, Bacterial, Sepsis, Adhesins, Bacterial, Bacterial Translocation, Lectins, Mice
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