Nosocomial infection characteristics in a burn intensive care unit: Analysis of an eleven-year active surveillance

Öncül, Oral; Öksüz, Si̇nan; Acar, Ali; Ülkür, Ersi̇n; Turhan, Vedat; Uygur, Fatih; Ülçay, Asım; Erdem, Hakan; Özyurt, Mustafa; Görenek, Levent

doi:10.1016/j.burns.2013.11.003

Cited by 84 publications

(44 citation statements)

References 29 publications

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“…P. aeruginosa has many adaptive mechanisms that allow it to thrive in a range of environmental conditions [1][2][3][4][5] , and is considered a model pathogen for both antibiotic-resistance and biofilm formation. Its recalcitrance and adaptive abilities contribute to the colonization of P. aeruginosa and its persistence in a variety of chronic infections 6,7 , including those in the lungs of patients with the fatal genetic disease cystic fibrosis (CF) [8][9][10] . Historically these bacterial communities have been characterized by examining the communal genotype [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Tracking the Dynamic Relationship between Cellular Systems and Extracellular Subproteomes in Pseudomonas aeruginosa Biofilms

et al. 2015

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The transition of the opportunistic pathogen Pseudomonas aeruginosa from free-living bacteria into surface-associated biofilm communities represents a viable target for the prevention and treatment of chronic infectious disease. We have established a proteomics platform that identified 2443 and 1142 high-confidence proteins in P. aeruginosa whole cells and outer-membrane vesicles (OMVs), respectively, at three time points during biofilm development (ProteomeXchange identifier PXD002605). The analysis of cellular systems, specifically the phenazine biosynthetic pathway, demonstrates that whole-cell protein abundance correlates to end product (i.e., pyocyanin) concentrations in biofilm but not in planktonic cultures. Furthermore, increased cellular protein abundance in this pathway results in quantifiable pyocyanin in early biofilm OMVs and OMVs from both growth modes isolated at later time points. Overall, our data indicate that the OMVs being released from the surface of the biofilm whole cells have unique proteomes in comparison to their planktonic counterparts. The relative abundance of OMV proteins from various subcellular sources showed considerable differences between the two growth modes over time, supporting the existence and preferential activation of multiple OMV biogenesis mechanisms under different conditions. The consistent detection of cytoplasmic proteins in all of the OMV subproteomes challenges the notion that OMVs are composed of outer membrane and periplasmic proteins alone. Direct comparisons of outer-membrane protein abundance levels between OMVs and whole cells shows ratios that vary greatly from 1:1 and supports previous studies that advocate the specific inclusion, or "packaging", of proteins into OMVs. The quantitative analysis of packaged protein groups suggests biogenesis mechanisms that involve untethered, rather than absent, peptidoglycan-binding proteins. Collectively, individual protein and biological system analyses of biofilm OMVs show that drug-binding cytoplasmic proteins and porins are potentially shuttled from the whole cell into the OMVs and may contribute to the antibiotic resistance of P. aeruginosa whole cells within biofilms.

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Section: Introductionmentioning

confidence: 99%

Tracking the Dynamic Relationship between Cellular Systems and Extracellular Subproteomes in Pseudomonas aeruginosa Biofilms

et al. 2015

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“…The opportunistic pathogen Pseudomonas aeruginosa is a common agent of infectious disease in immunocompromised individuals (Afessa and Green, 2000; Öncül et al, 2013; Chatterjee et al, 2014), and is the dominant pathogen in late-stage cystic fibrosis (CF; Rajan and Saiman, 2002; Rudkjobing et al, 2012). P. aeruginosa has many features that make it intrinsically resistant to antimicrobial therapies, including a low membrane permeability (Angus et al, 1982; Yoshimura and Nikaido, 1982), and an extensive collection of multidrug eﬄux pumps (Li et al, 1995, 2003; Poole et al, 1996; Köhler et al, 1997; Morita et al, 2001; Aendekerk et al, 2002; Chuanchuen et al, 2002; Mima et al, 2005, 2007, 2009; Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial targets localize to the extracellular vesicle-associated proteome of Pseudomonas aeruginosa grown in a biofilm

2014

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Microbial biofilms are particularly resistant to antimicrobial therapies. These surface-attached communities are protected against host defenses and pharmacotherapy by a self-produced matrix that surrounds and fortifies them. Recent proteomic evidence also suggests that some bacteria, including the opportunistic pathogen Pseudomonas aeruginosa, undergo modifications within a biofilm that make them uniquely resistant compared to their planktonic (free-living) counterparts. This study examines 50 proteins in the resistance subproteome of both surface-associated and free-living P. aeruginosa PAO1 over three time points. Proteins were grouped into categories based on their roles in antimicrobial: (i) binding, (ii) eﬄux, (iii) resistance, and (iv) susceptibility. In addition, the extracellular outer membrane vesicle-associated proteome is examined and compared between the two growth modes. We show that in whole cells between 12–24% of the proteins are present at significantly different abundance levels over time, with some proteins being unique to a specific growth mode; however, the total abundance levels in the four categories remain consistent. In contrast, marked differences are seen in the protein content of the outer membrane vesicles, which contain a greater number of drug-binding proteins in vesicles purified from late-stage biofilms. These results show how the method of analysis can impact the interpretation of proteomic data (i.e., individual proteins vs. systems), and highlight the advantage of using protein-based methods to identify potential antimicrobial resistance mechanisms in extracellular sample components. Furthermore, this information has the potential to inform the development of specific antipseudomonal therapies that quench possible drug-sequestering vesicle proteins. This strategy could serve as a novel approach for combating the high-level of antimicrobial resistance in P. aeruginosa biofilms.

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“…The Gram-negative bacterium Pseudomonas aeruginosa is frequently associated with hospital acquired infections78 and is found in approximately 33% of all burn wounds and in 59% of extensive burns1. Due to drug efflux mechanisms and genetically acquired drug resistance, P. aeruginosa is extremely antibiotic tolerant9.…”

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confidence: 99%

Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury

Huebinger

Stones

Santos

et al. 2016

Sci Rep

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Classical antimicrobial drugs target proliferation and therefore place microbes under extreme selective pressure to evolve resistance. Alternative drugs that target bacterial virulence without impacting survival directly offer an attractive solution to this problem, but to date few such molecules have been discovered. We previously discovered a widespread group of bacterial adhesins, termed Multivalent Adhesion Molecules (MAMs) that are essential for initial binding of bacteria to host tissues and virulence. Thus, targeting MAM-based adherence is a promising strategy for displacing pathogens from host tissues and inhibiting infection. Here, we show that topical application of polymeric microbeads functionalized with the adhesin MAM7 to a burn infected with multidrug-resistant Pseudomonas aeruginosa substantially decreased bacterial loads in the wound and prevented the spread of the infection into adjacent tissues. As a consequence, the application of this adhesion inhibitor allowed for vascularization and wound healing, and maintained local and systemic inflammatory responses to the burn. We propose that MAM7-functionalized microbeads can be used as a topical treatment, to reduce bacterial attachment and hence prevent bacterial colonization and infection of wounds. As adhesion is not required for microbial survival, this anti-infective strategy has the potential to treat multidrug-resistant infections and limit the emergence of drug-resistant pathogens.

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Nosocomial infection characteristics in a burn intensive care unit: Analysis of an eleven-year active surveillance

Cited by 84 publications

References 29 publications

Tracking the Dynamic Relationship between Cellular Systems and Extracellular Subproteomes in Pseudomonas aeruginosa Biofilms

Tracking the Dynamic Relationship between Cellular Systems and Extracellular Subproteomes in Pseudomonas aeruginosa Biofilms

Antimicrobial targets localize to the extracellular vesicle-associated proteome of Pseudomonas aeruginosa grown in a biofilm

Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury

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