Pseudomonas, Ear Cartilage and Cell-to-Cell Signaling
Abstract & Commentary
Synopsis: The interaction of cell to cell negative with cell to cell positive may be the crucial consideration between real patients.
Sources: Keene WE, et al. Outbreak of Psedomononas aeruginosa infections caused by commercial piercing of upper ear cartilage. JAMA. 2004;291:981-985; Denervaud V, et al. Characterization of cell-to-cell signaling-deficient Psedomononas aeruginosa strains colonizing intubated patients. J Clin Microbial. 2004;42:554-562.
Ear and body piercing are back in the news again. This time it involves the devastating infections of ear cartilage. An astute ENT physician in Klamath Falls, Oregon alerted his local health department about a girl whose ear has been pierced at a jewelry kiosk that the physician suspected of infecting another of his patient’s ear.
The subsequent investigation performed by the Acute & Communicable Disease Program in Portland with assistance from the Department of Environmental Health of the University of Washington provided great insight into these iatrogenic infections.
The review by William Keene and colleagues consisted of 118 patients who were interviewed about their 186 piercings over a 45-day period. Confirmed Pseudomonas aeruginosa infections were uncovered in 7 patients age 10 to 19 years (4%). Staphyloccus aureus was cultured from 1 patient. Of the 186 piercings, 63 were done in upper ear cartilage, and that site carried a relative risk of 3.6 during the study period. One worker was associated with 6 of 7 proven infections and 4 of 18 suspected infections.
Symptoms began anywhere from 3 hours to 3 days after piercing. All had pain, swelling, drainage and bleeding. Evidence of an abscess was present in all. Four patients required hospitalization.
What about the kiosk? It had been in business for 8 months before the outbreak. The operators had already been cited for "improper record keeping, hand washing, and equipment disinfection practices." The open spring-loaded guns used for the piercings were approved for lobes but not for cartilage. A disinfection atomizer has been used for months and 1 worker used it regularly to spray the equipment before firing the gun.
The isolate of P. areuginosa from the atomizer when analyzed by microrestriction analysis was the same at the 7 patient isolates. A sink trap had the same MRF pattern from a sink trap isolate was identical. Isolates from the community comprised up to 12 heterogenous patterns.
The photographs of 3 patients portrayed in vivid color emphasize the recalcitrant nature of these infections and the resultant cosmetic deformities. Interestingly, many otolaryngologists in Oregon had seen similar cases and only 29% had never seen a case of auricular chondritis.
Several new studies are defining the virulence factors of P. Aeruginosa and the molecular regulation of these virulence factors. Strains that produce factors like elastase, total exoprotease, and rhamnolipids are more often associated with infections. These virulence factors are regulated by at least 2 cell-to-cell signaling systems, called lasRI and rhlRI. The products of LastI and RhlI enzymes are lactones that allow Pseudomonas to sense their own cell density that once increased to a certain point will stimulate virulence factor production.
Recently, Denervaud and colleagues in Switzerland studied strains of P. aeruginosa isolated from intubated patients.1 They collected 442 isolates from 13 patients. Nine strains were genotypically distinct and in these 9, 6 showed strong cell-to-cell signaling. The other strains were cell-to-cell deficient mutants, a genotype that has been shown to be less virulent in animal models.
Biofilm was produced in 8 of the 9 strains studied, but the biofilm was not as intense as in cystic fibrosis isolates, but adherence was not decreased in cell-to-cell signaling mutants. The story becomes even more complex when compared to other observations that certain secretion systems are more important than cell-to-cell signaling. Finally, the interaction of cell-to-cell negative with cell-to-cell positive strains may be the crucial consideration in real patients.
Comment by Joseph F. John, MD
P. aeruginosa continues to be a "bad bug." It has intrinsic ability to be resistant to antimicrobials and further ability to obtain new resistance determinants from its environment. It easily colonized mucosal surfaces and produces factors that are injurious to human tissue. Finally, it is notorious for its penchant to colonize various medical solutions including ones that have no carbon sources. Taken together, these traits say this is not a bacterium to introduce iatrogenically into tissue.
The ear piercing debacle needed several components to work together to produce the outbreak. Eventually, 1 sanitizing atomizer became contaminated. The ear piercing procedure used blunt studs that were highly traumatic to tissue. The tissue traumatized was cartilage, known for its lack of intrinsic antibacterial defenses. Finally, empiric treatment was usually with a non-antipseudomonal beta-lactam which allowed the pseudomonas to gain a foothold in biofilm formatin and possibly to upregulate its virulence factor expression through cell-to-cell signaling.
The disastrous outcome in auricular chondritis emphasizes again the limited role of current antibacterials against superbugs like P. Aeruginosa and community MRSA. Understanding how we can interrupt virulence expression in these 2 bacteria will open new frontiers in treating infectious diseases. I can see the day in the not-too-distant future when an infection like auricular chondritis would be treated with a local cytokine inhibitor, an agent that disabled bacterial cell-to-cell signaling, and an antimicrobial that was rapidly bactericidal. We are not there yet, but studies like that of Denervaud suggests that future is not far away.
Joseph F. John, Jr., MD Chief, Medical Subspecialty Services, Ralph H. Johnson Veterans Administration Medical Center; Professor of Medicine, Medical University of South Carolina, Charleston, SC, is Co-Editor of Infectious Disease Alert.