Quorum sensing (QS)-based transcriptional reactions in have been defined on the basis of raises in transcript levels of QS-controlled genes such as and following a hierarchical transcriptional raises of central controllers such as the gene. early log phase. There were significant (< 0.05) but weak-to-modest correlations of transcript levels with (r2 = 0.2) and (strains with the highest levels of transcripts in early stationary phase. There were no variations in distribution of alleles among the bacteremia, pneumonia, or environmental isolates. Overall, only about 50% of strains from medical and environmental sources display a and genes, indicating that for about 50% of medical isolates this regulatory system may not P005091 supplier play a significant part in pathogenesis. is definitely a ubiquitous environmental organism able to colonize and infect humans with underlying genetic susceptibilities (14) or under opportunistic conditions. Ventilated individuals hospitalized in rigorous care units are often highly susceptible to colonization in the top respiratory tract (throat and/or trachea) (1, 8). The transition from colonization to illness by is often seen in the establishing of immunosuppression of sponsor defenses such as occurs in malignancy patients undergoing chemotherapy, when the blood levels of polymorphonuclear neutrophils are below 100/mm3 (26). In addition, controlled transcription and synthesis of genes and proteins involved in virulence G-CSF are thought to be instrumental in sensing the sponsor environment and generating appropriate bacterial reactions. The transcription of genes encoding several virulence factors of is controlled by the two quorum-sensing (QS) systems, and (19), which are regulated by autoinducers (30). Our knowledge of these two QS systems in offers rapidly progressed in the last decade (for a recent review, see research 4). The system settings the manifestation of virulence genes such as (6, 7, 17, 23, 28). The system controls, for example, the manifestation of (2, 3, 11, 12, 15, 18, 30). The and QS systems are hierarchically linked. The system positively regulates the manifestation of both and (11, 19). In vitro studies with primarily laboratory strains and virulence studies in animals with these same strains have suggested a role for QS systems in pathogenesis. However, the importance of QS in medical isolates from standard human infections is not clearly known (21). A recent study (25) showed a positive correlation between the build up of transcripts and those of in sputum samples from cystic fibrosis (CF) individuals infected with system settings virulence gene manifestation during the course of this specific illness. The autoinducers have also been recognized in sputum from individuals with CF that also experienced high levels of and transcripts (5, 24, 25). However, detection of the autoinducers and and P005091 supplier transcripts remained low for a number of CF patients infected by (5, 25), and due to the high immune reactions of CF individuals to virulence factors, it is unclear with this establishing of chronic illness whether QS-controlled proteins remain effective virulence factors. As there has been little investigation into the part of QS in strains outside of CF, it may be that some isolates do not possess or do not communicate the QS systems yet remain capable of causing serious human infections. In order to determine the presence and function of the QS gene among non-CF medical isolates, we analyzed the sequence of most of the gene from a collection of 66 strains isolated from instances of nosocomial pneumonia in ventilated individuals hospitalized in an rigorous care unit, from instances of bacteremia in malignancy individuals with neutropenia, and from water from swimming pools and rivers (20). A subset of these strains selected on the P005091 supplier basis of genetic diversity of the gene sequence and of the origin of strains was further used to quantify the amount of mRNA transcribed by genes during the growth of these strains by using P005091 supplier real-time reverse transcription-PCR. MATERIALS AND METHODS Bacterial strains and growth conditions. We analyzed 68 strains of mutant derived from P005091 supplier PAO1 (11); 30 strains isolated from individuals with nosocomial pneumonia; 20.