Howard Ceri

Quorum-sensing mutations affect attachment and stability of Burkholderia cenocepacia biofilms.

ABSTRACT Biofilm formation in Burkholderia cenocepacia has been shown to rely in part on acylhomoserine lactone-based quorum sensing. For many other bacterial species, it appears that both the initial adherence and the later stages of biofilm maturation are affected when quorum sensing pathways are inhibited. In this study, we examined the effects of mutations in the cepIR and cciIR quorum-sensing systems of Burkholderia cenocepacia K56-2 with respect to biofilm attachment and antibiotic resistance. We also examined the role of the cepIR system in biofilm stability and structural development. Using the high-throughput MBEC assay system to produce multiple equivalent biofilms, the biomasses of both the cepI and cepR mutant biofilms, measured by crystal violet staining, were less than half of the value observed for the wild-type strain. Attachment was partially restored upon providing functional gene copies via multicopy expression vectors. Surprisingly, neither the cciI mutant nor the double cciI cepI mutant was deficient in attachment, and restoration of the cciI gene resulted in less attachment than for the mutants. Meanwhile, the cciR mutant did show a significant reduction in attachment, as did the cciR cepIR mutant. While there was no change in antibiotic susceptibility with the individual cepIR and cciIR mutants, the cepI cciI mutant biofilms were more sensitive to ciprofloxacin. A significant increase in sensitivity to removal by sodium dodecyl sulfate was seen for the cepI and cepR mutants. Flow cell analysis of the individual cepIR mutant biofilms indicated that they were both structurally and temporally impaired in attachment and development. These results suggest that biofilm structural defects might be present in quorum-sensing mutants of B. cenocepacia that affect the stability and resistance of the adherent cell mass, providing a basis for future studies to design preventative measures against biofilm formation in this species, an important lung pathogen of cystic fibrosis patients.

Psychosocial variables affect the quality of life of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome

To examine interactions between demographic, pain, urinary, psychological and environmental predictors of quality of life (QOL) in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Antibiotic pharmacokinetics in the inflamed prostate.

We hypothesized that altered pharmacokinetics in the inflamed prostate gland might account for the treatment failure of clinically diagnosed chronic bacterial prostatitis. We employed a rat model of chronic bacterial prostatitis to investigate any pharmacokinetic differences that may exist between uninflamed and inflamed prostate glands. Four groups of animals were studied (treated and untreated control and prostatitis groups). Seven days of norfloxacin therapy cured 60% of the animals with well-established bacterial prostatitis compared with a spontaneous cure rate of 10% in the nontreated prostatitis animals. Norfloxacin levels did not change significantly between the infected and noninfected prostate glands. We conclude that failure of antibiotic therapy in chronic bacterial prostatitis is not due to significantly altered norfloxacin pharmacokinetics in the chronically inflamed prostate gland but rather to the difficulty of eradicating protected bacterial microcolonies within an infection-induced altered microenvironment deep within the prostate gland.