Abstract
Secreted virulence factors of the human pathogen Pseudomonas aeruginosa are often under quorum sensing control. Cells lacking the quorum-sensing regulator LasR show reduced virulence factor production under typical laboratory conditions and are hypo-virulent in short-term animal infection models, yet lasR mutants are frequently associated with long-term infection in cystic fibrosis patients. Here, I show that in stationary-phase or slow-growth conditions, lasR cells continuously and strongly produce the important virulence factor pyocyanin while wild-type cells do not. Pyocyanin overproduction by lasR cells is permitted by loss of repression by RsaL, a LasR-dependent negative regulator. lasR cells also contribute pyocyanin in mixed cultures, even under “cheating” conditions where they depend on their wild-type neighbors for nutrients. Finally, some clinical P. aeruginosa isolates with lasR mutations can overproduce pyocyanin in the laboratory. These results imply that slow-growing clinical populations of lasR cells in chronic infections may contribute to virulence by producing pyocyanin under conditions where lasR + cells do not.
Highlights
Pseudomonas aeruginosa is a common opportunistic bacterial pathogen that causes human infections in a variety of clinical situations [1] but is especially important in cystic fibrosis lung infections [2]
Cells grow to a high density that very gradually falls over the course of several days (Fig. 1B) but do not exhibit the ‘‘death phase’’ that typically precedes long-term adaptation to stationary phase [26]
Wild-type cells produce noticeable pyocyanin beginning in late exponential phase [4], while lasR cells begin to produce it by 24 h of culture [15]
Summary
Pseudomonas aeruginosa is a common opportunistic bacterial pathogen that causes human infections in a variety of clinical situations [1] but is especially important in cystic fibrosis lung infections [2]. Many of the numerous virulence factors produced by P. aeruginosa are under the control of quorum sensing, which uses diffusible autoinducer molecules as a way to monitor cell density [3]. Pyocyanin, a phenazine small molecule and virulence factor, acts as a terminal signaling factor in the quorum-sensing cascade [4]. Consistent with this hierarchy, inactivation of LasR, the regulatory protein of the Las quorumsensing system, has been reported to severely attenuate quorum sensing, the production of quorum-regulated factors, and virulence in typical laboratory culture and in short-term animal models [5,6,7,8,9,10,11]
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