Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections.

The ability of Pseudomonas aeruginosa to secrete specific toxins using the type III-mediated pathway has been reported. To determine the association of this phenotype with human illness, immunoblot analysis was used to detect expression of type III secretory proteins in P. aeruginosa isolates from respiratory tract or blood cultures of 108 consecutive patients. Relative risk of mortality was 6-fold greater with expression of the type III secretory proteins ExoS, ExoT, ExoU, or PcrV. Phenotype was independently correlated with toxicity in cellular and murine models. Prevalence of this phenotype was significantly higher in acutely infected patients than in chronically infected patients with cystic fibrosis. These results suggest that the type III protein secretion system is integral to increased P. aeruginosa virulence. A positive phenotype is a predictor of poor clinical outcome. In the future, such analyses may help distinguish potentially lethal infection from colonization and help determine appropriate therapy for critically ill patients.

Novel HPV types present in oral papillomatous lesions from patients with HIV infection.

Patients infected with the human immunodeficiency virus (HIV) often develop multiple papillomatous lesions of the oral cavity. In the present study, a total of 67 biopsies from benign oral lesions were analyzed for the presence of human papillomavirus (HPV) DNA using Southern-blot hybridization in combination with a polymerase chain reaction designed to detect all known HPV types, as well as unidentified types. These samples, collected at random from a high-risk population, were subsequently divided into 57 biopsies originating from patients with confirmed HIV infection and 10 biopsies from patients with unknown HIV status. Each sample was amplified with 7 different combinations of degenerate primers. All amplified products were sequenced. HPV DNA sequences were detected in 67% (45/67) of the samples. HPV 7 (19%) and HPV 32 (28%) were the predominant HPV types. HPV 32 was present in 2/4 fibromas tested. Two new HPV types, HPV 72 and HPV 73, were identified in oral warts with atypia. The complete genomes of these viruses were cloned and sequenced. Other HPV types detected were HPV 2a, HPV 6b, HPV 13, HPV 16, HPV 18, HPV 55, HPV 59 and HPV 69.

Nucleotide sequence and phylogenetic classification of human papillomavirus type 59.

The complete nucleotide sequence of the HPV 59 DNA genome, isolated from a vulvar intraepithelial neoplasia, was determined. It consists of 7896 nucleotides. A comparative analysis of this sequence with the sequences of other HPV types revealed the closest homology to HPV 18 (71%), HPV 45 (70%), and HPV 39 (69%). Phylogenetic analysis of the complete L1 ORFs of HPV 59 and other papillomaviruses exclusively groups all HPVs which have been detected in mucosal lesions into one major branch. This major branch, in turn, includes two specific subgroups containing all high risk viruses associated with malignant mucosal lesions. The motif in the L2 ORF thr-thr-pro-ala-val/ile-leu/ile-asp/asn-val/ile, an extension of a previously reported mucosal motif, is highly conserved in all HPV types detected in mucosal lesions, whereas it is totally absent in those viruses exclusively associated with cutaneous lesions.