Pseudomonas aeruginosa and microbial endocrinology

I recently presented the “Recognition of intestinal epithelial HIF-1a activation by Pseudomonas aeruginosa” by Patel et al. in a journal club discussion.  This group at the University of Chicago led by Eugene Chang and John C. Alverdy try to understand why P. aeruginosa seems to become very active in the intestines after certain surgical procedures. Their previous work described how a laparotomy (opening of the chest cavity) did not induce mortality in mice injected with PA in the cecum, while a partial hepatectomy followed by the injection caused 100% mortality. They reasoned that surgical stress made the bacteria more active (i.e. pathogenic). They focus on a gene that is important for PA’s initial opportunistic adherence called PA-I lectin/adhesin. An interesting paper in Science, which made me look into this group, shows that IFNg, an inflammatory cytokine, can bind to a surface protein of the bacterium and induce changes in transcription. They’ve also published about the effects of dynorphin, an endogeous opioid, on the bacteria’s gene expression.  In this paper, they show that hypoxia, common during surgery, sets off a chain of events that can activate PA.

The paper showed how ischemia-reperfusion injury can activate PA. The temporary loss of oxygen to an organ [ischemia] causes some damage, but after prolonged loss of oxygen, reoxygenation can be more damaging as reactive oxygen species [ROS] are released [reperfusion injury]. During ischemia (and a lot of other processes, including some considered oncogenic), hypoxia-inducible factors (HIF) is released setting of a chain of events. As a brief summary, HIF-1a causes the release of lots of adenosine (I think by breaking down ATP), which is supposed to help protect the epithelium by making tight junctions tighter and not allowing neutrophils to get by (source of ROS which may be damaging the host?). It’s been reported that PA-I lectin in addition to its binding of galactose, could bind N-acyl homoserine lactones (quorum sensing molecules) and adenine. Patel et al. demonstrated that adenosine is processed by PA using an adenosine deaminase, causing the activation of PA-I lectin.

Being my first entry, I got a bit carried away with the length. The main take home message from the discussion was that bacteria are capable of not only reacting to the consequences of host responses but that they can at times respond to the mediators/signals used by the body to activate the responses. This gives them a slight edge as they can anticipate and adapt to the host’s next move.

There are interesting reviews by Mark Lyte (who coined the words “microbial endocrinology” for this reemerging field [reemerging according to Moselio Schaechter from "Small Things Considered"]) or Vanessa Sperandio (who coined “inter-kingdom signaling“). They’ve separately worked a lot on how catecholamines (epinephrine and norepinephrine AKA aderenaline and noradrenaline) can induce growth, adhesion, etc. on E. coli. There are cool papers out there about how IL-2, IL-1B, TNFa and others are being shown to have an effect on many bugs like E. coli, P. aeruginosa, Vibrio, etc. so check out the links below.

Global Effects of the Cell-to-Cell Signaling Molecules Autoinducer-2, Autoinducer-3, and Epinephrine in a luxS Mutant of Enterohemorrhagic Escherichia coli

Catecholamine induced growth of gram negative bacteria

Enhancement of growth of virulent strains of Escherichia coli by IL-1

IL-2 and GM-CSF stimulate growth of a virulent strain of Escherichia coli

Modulation of Bacterial Growth by TNFa In Vitro and In Vivo

Blocking catecholamine-induced growth in E. coli O157:H7, Salmonella enterica and Yersinia enterocolitica

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