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1.
PLoS Pathog ; 17(2): e1009304, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33544760

RESUMEN

S. epidermidis is a substantial component of the human skin microbiota, but also one of the major causes of nosocomial infection in the context of implanted medical devices. We here aimed to advance the understanding of S. epidermidis genotypes and phenotypes conducive to infection establishment. Furthermore, we investigate the adaptation of individual clonal lines to the infection lifestyle based on the detailed analysis of individual S. epidermidis populations of 23 patients suffering from prosthetic joint infection. Analysis of invasive and colonizing S. epidermidis provided evidence that invasive S. epidermidis are characterized by infection-supporting phenotypes (e.g. increased biofilm formation, growth in nutrient poor media and antibiotic resistance), as well as specific genetic traits. The discriminating gene loci were almost exclusively assigned to the mobilome. Here, in addition to IS256 and SCCmec, chromosomally integrated phages was identified for the first time. These phenotypic and genotypic features were more likely present in isolates belonging to sequence type (ST) 2. By comparing seven patient-matched nasal and invasive S. epidermidis isolates belonging to identical genetic lineages, infection-associated phenotypic and genotypic changes were documented. Besides increased biofilm production, the invasive isolates were characterized by better growth in nutrient-poor media and reduced hemolysis. By examining several colonies grown in parallel from each infection, evidence for genetic within-host population heterogeneity was obtained. Importantly, subpopulations carrying IS insertions in agrC, mutations in the acetate kinase (AckA) and deletions in the SCCmec element emerged in several infections. In summary, these results shed light on the multifactorial processes of infection adaptation and demonstrate how S. epidermidis is able to flexibly repurpose and edit factors important for colonization to facilitate survival in hostile infection environments.

2.
Eur Spine J ; 2021 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-33423133

RESUMEN

PURPOSE: Surgical intervention with intercorporal stabilisation in spinal infections is increasingly needed. Our aim was to compare titanium and polyetheretherketon (PEEK) cages according to their adhesion characteristics of different bacteria species in vitro. METHODS: Plates made from PEEK, polished titanium (Ti), two-surface-titanium (TiMe) (n = 2-3) and original PEEK and porous trabecular structured titanium (TiLi) interbody cages (n = 4) were inoculated in different bacterial solutions, S.aureus (MSSA, MRSA), S.epidermidis and E.coli. Growth characteristics were analysed. Biofilms and bacteria were visualised using confocal- and electron microscopy. RESULTS: Quantitative adherence of MSSA, MRSA, S.epidermidis and E.coli to Ti, TiMe and PEEK plates were different, with polished titanium being mainly advantageous over PEEK and TiMe with significantly less counts of colony forming units (CFU) for MRSA after 56 h compared to TiMe and at 72 h compared to PEEK (p = 0.04 and p = 0.005). For MSSA, more adherent bacteria were detected on PEEK than on TiMe at 32 h (p = 0.02). For PEEK and TiLi cages, significant differences were found after 8 and 72 h for S.epidermidis (p = 0.02 and p = 0.008) and after 72 h for MSSA (p = 0.002) with higher bacterial counts on PEEK, whereas E.coli showed more CFU on TiLi than PEEK (p = 0.05). Electron microscopy demonstrated enhanced adhesion in transition areas. CONCLUSION: For S.epidermidis, MSSA and MRSA PEEK cages showed a higher adherence in terms of CFU count, whereas for E.coli PEEK seemed to be advantageous. Electron microscopic visualisation shows that bacteria did not adhere at the titanium mesh structure, but at the border zones of polished material to rougher parts.

3.
mBio ; 11(5)2020 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-33082256

RESUMEN

Although it is normally an innocuous part of the human skin microbiota, Staphylococcus epidermidis has emerged as a major nosocomial pathogen, and implanted foreign materials are an essential risk factor for the development of an infection. The extraordinary efficiency of S. epidermidis to colonize artificial surfaces is particularly related to the ability to form biofilms. Biofilm formation itself critically depends on stable pathogen binding to extracellular host matrix components, e.g. fibronectin (Fn), covering inserted devices in vast amounts. Extracellular matrix binding protein (Embp) and its subdomains referred to as the F-repeat and the FG-repeat are critical for adherence of S. epidermidis to surface-immobilized Fn. Embp-Fn interactions preferentially occur with surface-bound, but not folded, globular Fn via binding to the F3 domain. High-resolution structure analysis of F- and FG-repeats revealed that both repeats are composed of two tightly connected triple α-helix bundles, exhibiting an elongated but rather rigid structural organization in solution. Both F- and FG-repeat possess Fn-binding capacity via interactions with type III subdomain FN12, involving residues within the C and F ß-sheet. FN12 essentially supports stability of the globular Fn state, and thus these findings reasonably explain why Embp-mediated interaction of S. epidermidis necessitates Fn surface immobilization. Thus, Embp employs an uncharacterized bacterial Fn-binding mechanism to promote staphylococcal adherence.IMPORTANCE Staphylococcus epidermidis is a leading pathogen in implant-associated hospital infections. The pathogenesis critically depends on bacterial binding to ECM components, specifically fibronectin (Fn). The cell surface-localized, 1-MDa extracellular matrix binding protein (Embp) is essentially characterized by 10 F- and 40 FG-repeats. These repetitive units, each characterized by two α-helical bundles, organize themselves in a rigid, elongated form. Embp binds preferentially to surface-localized but not soluble Fn, with both F- and FG-repeats being sufficient for Fn binding and resulting bacterial adherence. Binding preferentially involves Fn type III domain, specifically residues of FN12 ß-sheets C and F. Both play key role in stabilizing the globular Fn conformation, explaining the necessity of Fn surface immobilization for a subsequent interaction with Embp. In comparison to many other bacterial Fn-binding proteins using the Fn N terminus, Embp employs a previously undescribed mechanism supporting the adhesion of S. epidermidis to surface-immobilized Fn.

4.
Expert Rev Anti Infect Ther ; 18(4): 349-366, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32056452

RESUMEN

Introduction: Compared to Staphylococcus aureus, coagulase-negative staphylococci (CoNS) are characterized by a lower capacity to cause acute, live-threatened infections. CoNS are, however, of ever increasing importance as pathogens causing infections in immunocompromised patients and after foreign-material implantation. Typically, antibiotics fail to cure foreign body-related infections and removal of the implanted device is inevitable.Areas covered: This review focuses on the emergence of CoNS species, their pathogenic potential in particular due to their ability to form therapy-refractory biofilms on biotic and abiotic surfaces and evasion strategies to resist host response and antibiotic treatment. Their medical significance and proven and novel therapy strategies are discussed.Expert opinion: CoNS contribute significantly to morbidity and socio-economic costs. The anticipated developments in modern medicine, in particular the increasing use of foreign materials and the rising numbers of immunocompromised patients, as well as the changing demographic and hospital-related factors will inevitably contribute to further emergence of CoNS infections. Increasing rates of (multi-)resistant CoNS strains will limit the therapeutic armamentarium and aggravate treatment strategies. Increased research is necessary to understand their role as resistance and virulence gene reservoir and to reduce CoNS infections by the development of innovative colonization-preventing materials and other CoNS-tailored treatment strategies.

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