No abstract

Purpose Biofilm infections have a major role in implants or devices placed in the human body. As part of the endourological development, a great variety of foreign bodies have been designed, and with the increasing number of biomaterial devices used in urology, biofilm formation and device infection is an issue of growing importance. Methods A literature search was performed in the Medline database regarding biofilm formation and the role of biofilms in urogenital infections using the following items in different combinations: “biofilm,” “urinary tract infection,” “bacteriuria,” “catheter,” “stent,” and “encrustation.” The studies were graded using the Oxford Centre for Evidence-based Medicine classification. Results The authors present an update on the mechanism of biofilm formation in the urinary tract with special emphasis on the role of biofilms in lower and upper urinary tract infections, as well as on biofilm formation on foreign bodies, such as catheters, ureteral stents, stones, implants, and artificial urinary sphincters. The authors also summarize the different methods developed to prevent biofilm formation on urinary foreign bodies. Conclusions Several different approaches are being investigated for preventing biofilm formation, and some promising results have been obtained. However, an ideal method has not been developed. Future researches have to aim at identifying effective mechanisms for controlling biofilm formation and to develop antimicrobial agents effective against bacteria in biofilms.

Both local and systemic infections may complicate the morbidity of patients with oral malignant neoplasms, particularly those presenting intraorally. This study investigated the microbial contents of the biofilms present on the surfaces of oral squamous cell carcinomas. Biofilm samples were obtained from the central surface of the lesions in 21 patients (20 male, 1 female) aged 52.8 (+/- 8.2) years, and from contiguous healthy mucosa, before any antibiotic therapy or any tumour treatment. All lesions were keratinising squamous cell carcinomas with surface ulceration. Samples were transported in reduced brain heart infusion (BHI) broth and cultured within 1 h of removal, using aerobic and anaerobic complete and selective media. The median number of anaerobic colony forming units (CFU/ml) at the tumour sites (1.6 x 10(8)) was significantly higher than for the healthy (control) mucosa (3.0 x 10(7); P = 0.0001, Wilcoxon); the same was true for aerobes at the tumour sites (1.51 x 10(8)) relative to the controls (2.8 x 10(7); P = 0.0008, Wilcoxon). The species isolated in increased numbers at tumour sites were Veillonella, Fusobacterium, Prevotella, Porphyromonas, Actinomyces and Clostridium (anaerobes), and Haemophilus, Enterobacteriaceae and Streptococcus spp. (aerobes). Candida albicans was found at eight of the 21 tumour sites, but never at control sites. It was concluded that human oral carcinoma surface biofilms harbour significantly increased numbers of aerobes and anaerobes as compared with the healthy mucosal surface of the same patient. Candida albicans can also be present in these biofilms. These findings must be considered in relation to the known predisposition of such patients to systemic infections, and to the unpleasant complications of oral morbidity due to infected lesions.

HTLV-producing T-cell lines induce cell fusion when co-cultivated with a wide variety of indicator cells, suggesting that HTLV envelope antigens interact with the membranes of many cell types. Serum antibodies from adult T-cell lymphoma-leukemia (ATL) patients inhibited the formation of syncytia, and sera from British, American and Japanese ATL patients inhibited cell fusion induced by American and Japanese HTLV isolates equally well. No serological cross-inhibition of syncytium induction was found between HTLV and bovine leukosis virus, Moloney murine leukemia virus and simian sarcoma-associated virus. A simple syncytium inhibition test in microtiter plates has been developed to provide a rapid screen for antibodies presumed to be specific to HTLV envelope glycoproteins.

Human T-cell leukemia virus (HTLV), American PL isolate, was transmitted by cocultivation and by cell-free filtrates to a nonlymphoid human osteogenic sarcoma (HOS) cell line, designated HOS/PL, but not to nine other lines bearing receptors for HTLV. HOS and HOS/PL cells are not dependent on interleukin-2 and do not express interleukin-2 receptors that are recognized by anti-Tac monoclonal antibody. HTLV released by the Japanese MT2 cell line was also transmitted to HOS cells. The infected HOS cells release substantial titers of progeny HTLV which is antigenically indistinguishable from parental virus and is able to transform T cells.

Tissue damage is usually regarded as a necessary price to pay for successful elimination of pathogens by the innate immune defense. Yet, it is possible to distinguish protective from destructive effects of innate immune activation and selectively attenuate molecular nodes that create pathology. Here, we identify acute cystitis as an Interleukin-1 beta (IL-1β)-driven, hyper-inflammatory condition of the infected urinary bladder and IL-1 receptor blockade as a novel therapeutic strategy. Disease severity was controlled by the mechanism of IL-1β processing and mice with intact inflammasome function developed a moderate, self-limiting form of cystitis. The most severe form of acute cystitis was detected in mice lacking the inflammasome constituents ASC or NLRP-3. IL-1β processing was hyperactive in these mice, due to a new, non-canonical mechanism involving the matrix metalloproteinase 7- (MMP-7). ASC and NLRP-3 served as transcriptional repressors of MMP7 and as a result, Mmp7 was markedly overexpressed in the bladder epithelium of Asc -/- and Nlrp3 -/- mice. The resulting IL-1β hyper-activation loop included a large number of IL-1β-dependent pro-inflammatory genes and the IL-1 receptor antagonist Anakinra inhibited their expression and rescued susceptible Asc -/- mice from bladder pathology. An MMP inhibitor had a similar therapeutic effect. Finally, elevated levels of IL-1β and MMP-7 were detected in patients with acute cystitis, suggesting a potential role as biomarkers and immunotherapeutic targets. The results reproduce important aspects of human acute cystitis in the murine model and provide a comprehensive molecular framework for the pathogenesis and immunotherapy of acute cystitis, one of the most common infections in man.Trial RegistrationThe clinical studies were approved by the Human Ethics Committee at Lund University (approval numbers LU106-02, LU236-99 and Clinical Trial Registration RTP-A2003, International Committee of Medical Journal Editors, www.clinicaltrials.gov).

In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival.

Lowered fitness cost associated with resistance to fluoroquinolones was recently demonstrated to influence the clonal dynamics of methicillin-resistant Staphylococcus aureus (MRSA) in the health care setting. We investigated whether or not a similar mechanism impacts Klebsiella pneumoniae. The fitness of K. pneumoniae isolates from major international hospital clones (ST11, ST15, ST147) already showing high-level resistance to fluoroquinolones and of strains from three minor clones (ST25, ST274, ST1028) in which fluoroquinolone resistance was induced in vitro was tested in a propagation assay. Strains from major clones showed significantly less fitness cost than three of four fluoroquinolone-resistant derivatives of minor clone isolates. In addition, plasmids with CTX-M-15 type extended-spectrum β-lactamase (ESBL) genes were all retained in both major and minor clone isolates, irrespective of the strains' level of fluoroquinolone resistance, while each plasmid harboring SHV-type ESBLs had been lost during the induction of resistance. Major clone K. pneumoniae strains harbored more amino acid substitutions in the quinolone resistance determining regions (QRDRs) of the gyrA and parC genes than minor clone isolates. The presence of an active efflux system could be demonstrated in all fluoroquinolone-resistant derivatives of originally SHV-producing minor clone isolates but not in any CTX-M-15-producing strain. Further investigations are needed to expand and confirm our findings on a larger sample. In addition, a long-term observation of our ciprofloxacin-resistant minor clone isolates is required in order to elucidate whether or not they are capable of restoring their fitness while concomitantly retaining high minimum inhibitory concentration (MIC) values.