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      Irrelevance of Panton-Valentine leukocidin in hidradenitis suppurativa: results from a pilot, observational study

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          Abstract

          Panton-Valentine leukocidin (PVL) appears to be a virulence factor which, among others, can exacerbate the pathogenicity of Staphylococcus aureus infections, especially inducing severe necrotic, deep-seated skin infections, abscesses, and recurrences. These peculiarities have some overlaps with hidradenitis suppurativa (HS). Our main aim was to assess if S. aureus producing PVL could have some role in influencing clinical features and/or course of HS, specifically in the suppuration and recurrence of lesions. This pilot, mono-centric, observational study included all adult subjects affected with HS consecutively referring to our HS clinic over a 3-month period. Clinically evident suppuration and at least 2 weeks wash out from any antibiotic were the main inclusion criteria. Purulent material from HS skin lesions was collected with swabs in order to isolate micro-organisms, with specific regard to S. aureus. Detection of PVL was performed by real-time quantitative PCR (RT-qPCR). We also analyzed purulent material from suppurative skin lesions other than HS, as a control. Thirty HS patients were included; 29 purulent lesions (96.7%) harbored at least one bacterial species. Five (16.7%) swab samples were positive for S. aureus, none of which was positive for PVL genes. Among the 30 purulent disorders included as controls, 8 (26.3%) were positive for S. aureus; of these, 4 strains (50%) expressed LPV. The study results seem to exclude the pathogenetic involvement of S. aureus producing PVL in HS; as a result, PVL does not seem to represent a potential target in the future development of HS treatments.

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          The role of the Panton-Valentine leucocidin toxin in staphylococcal disease: a systematic review and meta-analysis

          Summary Background Invasive community-onset staphylococcal disease has emerged worldwide associated with Panton-Valentine leucocidin (PVL) toxin. Whether PVL is pathogenic or an epidemiological marker is unclear. We investigate the role of PVL in disease, colonisation, and clinical outcome. Methods We searched Medline and Embase for original research reporting the prevalence of PVL genes among Staphylococcus aureus pneumonia, bacteraemia, musculoskeletal infection, skin and soft-tissue infection, or colonisation published before Oct 1, 2011. We calculated odds ratios (ORs) to compare patients with PVL-positive colonisation and each infection relative to the odds of PVL-positive skin and soft-tissue infection. We did meta-analyses to estimate odds of infection or colonisation with a PVL-positive strain with fixed-effects or random-effects models, depending on the results of tests for heterogeneity. Results Of 509 articles identified by our search strategy, 76 studies from 31 countries met our inclusion criteria. PVL strains are strongly associated with skin and soft-tissue infections, but are comparatively rare in pneumonia (OR 0·37, 95% CI 0·22–0·63), musculoskeletal infections (0·44, 0·19–0·99), bacteraemias (0·10, 0·06–0·18), and colonising strains (0·07, 0·01–0·31). PVL-positive skin and soft-tissue infections are more likely to be treated surgically than are PVL-negative infections, and children with PVL-positive musculoskeletal disease might have increased morbidity. For other forms of disease we identified no evidence that PVL affects outcome. Interpretation PVL genes are consistently associated with skin and soft-tissue infections and are comparatively rare in invasive disease. This finding challenges the view that PVL mainly causes invasive disease with poor prognosis. Population-based studies are needed to define the role of PVL in mild, moderate, and severe disease and to inform control strategies. Funding None.
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            Staphylococcus aureus Panton-Valentine leukocidin directly targets mitochondria and induces Bax-independent apoptosis of human neutrophils.

            Panton-Valentine leukocidin (PVL) is a pore-forming toxin secreted by Staphylococcus aureus that has recently been associated with necrotizing pneumonia. In the present study, we report that in vitro, PVL induces polymorphonuclear cell death by necrosis or by apoptosis, depending on the PVL concentration. PVL-induced apoptosis was associated with a rapid disruption of mitochondrial homeostasis and activation of caspase-9 and caspase-3, suggesting that PVL-induced apoptosis is preferentially mediated by the mitochondrial pathway. Polymorphonuclear cell exposure to PVL leads to mitochondrial localization of the toxin, whereas Bax, 1 of the 2 essential proapoptotic members of the Bcl-2 family, was still localized in the cytosol. Addition of PVL to isolated mitochondria induced the release of the apoptogenic proteins cytochrome c and Smac/DIABLO. Therefore, we suggest that PVL, which belongs to the pore-forming toxin family, could act at the mitochondrion level by creating pores in the mitochondrial outer membrane. Furthermore, LukS-PV, 1 of the 2 components of PVL, was detected in lung sections of patients with necrotizing pneumonia together with DNA fragmentation, suggesting that PVL induces apoptosis in vivo and thereby is directly involved in the pathophysiology of necrotizing pneumonia.
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              Measurement of Pseudomonas aeruginosa phenazine pigments in sputum and assessment of their contribution to sputum sol toxicity for respiratory epithelium.

              The phenazine pigments pyocyanin and 1-hydroxyphenazine were resolved by high-pressure liquid chromatography from the sputum sol phase from 9 of 13 patients with cystic fibrosis or bronchiectasis colonized by Pseudomonas aeruginosa. The concentrations measured were each sufficient to inhibit ciliary beating in vitro and contributed a significant proportion of sol phase toxicity for respiratory epithelium.
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                Author and article information

                Contributors
                alessandro.borghi@unife.it
                Journal
                Eur J Clin Microbiol Infect Dis
                Eur J Clin Microbiol Infect Dis
                European Journal of Clinical Microbiology & Infectious Diseases
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0934-9723
                1435-4373
                7 August 2020
                7 August 2020
                2021
                : 40
                : 1
                : 77-83
                Affiliations
                [1 ]GRID grid.8484.0, ISNI 0000 0004 1757 2064, Section of Dermatology and Infectious Diseases, Department of Medical Sciences, , University of Ferrara, ; Via L. Ariosto 35, 44121 Ferrara, Italy
                [2 ]GRID grid.416315.4, Analysis Laboratory, , S. Anna University Hospital, ; Ferrara, Italy
                [3 ]GRID grid.8484.0, ISNI 0000 0004 1757 2064, Laboratories of Cell Biology and Molecular Genetics, Section of Pathology, Oncology and Experimental Biology, Department of Morphology, Surgery and Experimental Medicine, , University of Ferrara, ; Ferrara, Italy
                [4 ]Palermo, Italy
                Author information
                https://orcid.org/0000-0001-9163-9691
                Article
                4002
                10.1007/s10096-020-04002-7
                7782376
                32767177
                d845f1b2-21a1-4788-a8c3-d2ba5b707b70
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 July 2020
                : 30 July 2020
                Funding
                Funded by: This study was supported by the Fondo per l’Incentivazione alla Ricerca (FIR) 2018
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2021

                Infectious disease & Microbiology
                hidradenitis suppurativa,panton-valentine leukocidin,staphylococcus aureus,infections,rt-qpcr

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