scholarly journals Fighting Staphylococcus epidermidis Biofilm-Associated Infections: Can Iron Be the Key to Success?

2021 ◽  
Vol 11 ◽  
Author(s):  
Fernando Oliveira ◽  
Holger Rohde ◽  
Manuel Vilanova ◽  
Nuno Cerca
Keyword(s):  
Iron Metabolism ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Iron Acquisition ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Formation Mechanisms ◽  
Bacterial Genes ◽  
Amount Of Knowledge ◽  
Biofilm Development

Staphylococcus epidermidis is one of the most important commensal microorganisms of human skin and mucosae. However, this bacterial species is also the cause of severe infections in immunocompromised patients, specially associated with the utilization of indwelling medical devices, that often serve as a scaffold for biofilm formation. S. epidermidis strains are often multidrug resistant and its association with biofilm formation makes these infections hard to treat. Their remarkable ability to form biofilms is widely regarded as its major pathogenic determinant. Although a significant amount of knowledge on its biofilm formation mechanisms has been achieved, we still do not understand how the species survives when exposed to the host harsh environment during invasion. A previous RNA-seq study highlighted that iron-metabolism associated genes were the most up-regulated bacterial genes upon contact with human blood, which suggested that iron acquisition plays an important role in S. epidermidis biofilm development and escape from the host innate immune system. In this perspective article, we review the available literature on the role of iron metabolism on S. epidermidis pathogenesis and propose that exploiting its dependence on iron could be pursued as a viable therapeutic alternative.

scholarly journals Quorum Sensing Influences Burkholderia thailandensis Biofilm Development and Matrix Production

2016 ◽  
Vol 198 (19) ◽  
pp. 2643-2650 ◽  
Author(s):  
Boo Shan Tseng ◽  
Charlotte D. Majerczyk ◽  
Daniel Passos da Silva ◽  
Josephine R. Chandler ◽  
E. Peter Greenberg ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Bacterial Species ◽  
Matrix Material ◽  
Close Relative ◽  
Wild Type ◽  
Flow Conditions ◽  
Burkholderia Thailandensis ◽  
Content Type ◽  
Biofilm Development

ABSTRACTMembers of the genusBurkholderiaare known to be adept at biofilm formation, which presumably assists in the survival of these organisms in the environment and the host. Biofilm formation has been linked to quorum sensing (QS) in several bacterial species. In this study, we characterizedBurkholderia thailandensisbiofilm development under flow conditions and sought to determine whether QS contributes to this process.B. thailandensisbiofilm formation exhibited an unusual pattern: the cells formed small aggregates and then proceeded to produce mature biofilms characterized by “dome” structures filled with biofilm matrix material. We showed that this process was dependent on QS.B. thailandensishas three acyl-homoserine lactone (AHL) QS systems (QS-1, QS-2, and QS-3). An AHL-negative strain produced biofilms consisting of cell aggregates but lacking the matrix-filled dome structures. This phenotype was rescued via exogenous addition of the three AHL signals. Of the threeB. thailandensisQS systems, we show that QS-1 is required for proper biofilm development, since abtaR1mutant, which is defective in QS-1 regulation, forms biofilms without these dome structures. Furthermore, our data show that the wild-type biofilm biomass, as well as the material inside the domes, stains with a fucose-binding lectin. ThebtaR1mutant biofilms, however, are negative for fucose staining. This suggests that the QS-1 system regulates the production of a fucose-containing exopolysaccharide in wild-type biofilms. Finally, we present data showing that QS ability during biofilm development produces a biofilm that is resistant to dispersion under stress conditions.IMPORTANCEThe saprophyteBurkholderia thailandensisis a close relative of the pathogenic bacteriumBurkholderia pseudomallei, the causative agent of melioidosis, which is contracted from its environmental reservoir. Since most bacteria in the environment reside in biofilms,B. thailandensisis an ideal model organism for investigating questions inBurkholderiaphysiology. In this study, we characterizedB. thailandensisbiofilm development and sought to determine if quorum sensing (QS) contributes to this process. Our work shows thatB. thailandensisproduces biofilms with unusual dome structures under flow conditions. Our findings suggest that these dome structures are filled with a QS-regulated, fucose-containing exopolysaccharide that may be involved in the resilience ofB. thailandensisbiofilms against changes in the nutritional environment.

scholarly journals Architectural transitions in Vibrio cholerae biofilms at single-cell resolution

2016 ◽  
Vol 113 (14) ◽  
pp. E2066-E2072 ◽  
Author(s):  
Knut Drescher ◽  
Jörn Dunkel ◽  
Carey D. Nadell ◽  
Sven van Teeffelen ◽  
Ivan Grnja ◽  
...  
Keyword(s):  
Single Cell ◽  
Vibrio Cholerae ◽  
Biofilm Formation ◽  
Bacterial Species ◽  
Bacterial Biomass ◽  
Biofilm Growth ◽  
Glass Substrates ◽  
Critical Transitions ◽  
Cell Shapes ◽  
Biofilm Development

Many bacterial species colonize surfaces and form dense 3D structures, known as biofilms, which are highly tolerant to antibiotics and constitute one of the major forms of bacterial biomass on Earth. Bacterial biofilms display remarkable changes during their development from initial attachment to maturity, yet the cellular architecture that gives rise to collective biofilm morphology during growth is largely unknown. Here, we use high-resolution optical microscopy to image all individual cells in Vibrio cholerae biofilms at different stages of development, including colonies that range in size from 2 to 4,500 cells. From these data, we extracted the precise 3D cellular arrangements, cell shapes, sizes, and global morphological features during biofilm growth on submerged glass substrates under flow. We discovered several critical transitions of the internal and external biofilm architectures that separate the major phases of V. cholerae biofilm growth. Optical imaging of biofilms with single-cell resolution provides a new window into biofilm formation that will prove invaluable to understanding the mechanics underlying biofilm development.

scholarly journals Pseudomonas aeruginosa secreted factors impair biofilm development in Candida albicans

Microbiology ◽  
2010 ◽  
Vol 156 (5) ◽  
pp. 1476-1486 ◽  
Author(s):  
Lucy J. Holcombe ◽  
Gordon McAlester ◽  
Carol A. Munro ◽  
Brice Enjalbert ◽  
Alistair J. P. Brown ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Candida Albicans ◽  
Biofilm Formation ◽  
Bacterial Species ◽  
Homoserine Lactone ◽  
Strong Increase ◽  
Opportunistic Pathogens ◽  
Secreted Factors ◽  
Expression Of Genes ◽  
Biofilm Development

Signal-mediated interactions between the human opportunistic pathogens Pseudomonas aeruginosa and Candida albicans affect virulence traits in both organisms. Phenotypic studies revealed that bacterial supernatant from four P. aeruginosa strains strongly reduced the ability of C. albicans to form biofilms on silicone. This was largely a consequence of inhibition of biofilm maturation, a phenomenon also observed with supernatant prepared from non-clinical bacterial species. The effects of supernatant on biofilm formation were not mediated via interference with the yeast–hyphal morphological switch and occurred regardless of the level of homoserine lactone (HSL) produced, indicating that the effect is HSL-independent. A transcriptome analysis to dissect the effects of the P. aeruginosa supernatants on gene expression in the early stages of C. albicans biofilm formation identified 238 genes that exhibited reproducible changes in expression in response to all four supernatants. In particular, there was a strong increase in the expression of genes related to drug or toxin efflux and a decrease in expression of genes associated with adhesion and biofilm formation. Furthermore, expression of YWP1, which encodes a protein known to inhibit biofilm formation, was significantly increased. Biofilm formation is a key aspect of C. albicans infections, therefore the capacity of P. aeruginosa to antagonize this has clear biomedical implications.

scholarly journals Aryl Rhodanines Specifically Inhibit Staphylococcal and Enterococcal Biofilm Formation

2009 ◽  
Vol 53 (10) ◽  
pp. 4357-4367 ◽  
Author(s):  
Timothy J. Opperman ◽  
Steven M. Kwasny ◽  
John D. Williams ◽  
Atiyya R. Khan ◽  
Norton P. Peet ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Small Molecules ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Antibiofilm Activity ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Artificial Surfaces ◽  
Causative Agents ◽  
Biofilm Development

ABSTRACT Staphylococcus epidermidis and Staphylococcus aureus are the leading causative agents of indwelling medical device infections because of their ability to form biofilms on artificial surfaces. Here we describe the antibiofilm activity of a class of small molecules, the aryl rhodanines, which specifically inhibit biofilm formation of S. aureus, S. epidermidis, Enterococcus faecalis, E. faecium, and E. gallinarum but not the gram-negative species Pseudomonas aeruginosa or Escherichia coli. The aryl rhodanines do not exhibit antibacterial activity against any of the bacterial strains tested and are not cytotoxic against HeLa cells. Preliminary mechanism-of-action studies revealed that the aryl rhodanines specifically inhibit the early stages of biofilm development by preventing attachment of the bacteria to surfaces.

scholarly journals Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics

2021 ◽  
Vol 12 ◽  
Author(s):  
Dejing Shang ◽  
Xue Han ◽  
Wanying Du ◽  
Zhiru Kou ◽  
Fengquan Jiang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Synergistic Effects ◽  
Multidrug Resistant ◽  
Biofilm Development ◽  
Antibiotic Efflux

Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence, biofilm formation and antibiotic efflux pump expression. The development of effective small molecules targeting the QS system and biofilm formation represents a novel attractive strategy. In this present study, the effects of a series of Trp-containing peptides on the QS-regulated virulence and biofilm development of multidrug-resistant P. aeruginosa, as well as their synergistic antibacterial activity with three classes of traditional chemical antibiotics were investigated. The results showed that Trp-containing peptides at low concentrations reduced the production of QS-regulated virulence factors by downregulating the gene expression of both the las and rhl systems in the strain MRPA0108. Biofilm formation was inhibited in a concentration-dependent manner, which was associated with extracellular polysaccharide production inhibition by downregulating pelA, algD, and pslA transcription. These changes correlated with alterations in the extracellular production of pseudomonal virulence factors and swarming motility. In addition, the combination of Trp-containing peptides at low concentration with the antibiotics ceftazidime and piperacillin provided synergistic effects. Notably, L11W and L12W showed the highest synergy with ceftazidime and piperacillin. A mechanistic study demonstrated that the Trp-containing peptides, especially L12W, significantly decreased β-lactamase activity and expression of efflux pump genes OprM, MexX, and MexA, resulting in a reduction in antibiotic efflux from MRPA0108 cells and thus increasing the antibacterial activity of these antibiotics against MRPA0108.

scholarly journals Genomic analysis of prevalent Staphylococcus epidermidis multidrug-resistant strains isolated during eight years in a single children hospital in México City.

2019 ◽  
Author(s):  
Roberto Cabrera-Contreras ◽  
Rosa I Santamaría ◽  
Patricia Bustos ◽  
Irma Martínez-Flores ◽  
Enrique Meléndez ◽  
...  
Keyword(s):  
Mexico City ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Antibiotic Resistant ◽  
Transfer Rates ◽  
Children Health ◽  
Health Care Unit

Staphylococcus epidermidis is a human commensal and pathogen worldwide distributed. In this work, we surveyed for multi-resistant S. epidermidis strains in eight years at a children health-care unit in México City. Multidrug-resistant S. epidermidis were present in all years of the study. Resistance to methicillin, beta-lactams, fluoroquinolones, and macrolides were included. To understand the genetic basis of antibiotic resistance and its association with virulence and gene exchange, we sequenced the genomes of 17 S. epidermidis isolates. Whole-genome nucleotide identities between all the pairs of S. epidermidis strains were about 97% to 99%. We inferred a clonal structure and eight Multilocus Sequence Types (MLST´s) in the S. epidermidis sequenced collection. The profile of virulence includes genes involved in biofilm formation and phenol-soluble modulins (PSMs). However, half of the S. epidermidis analyzed lacked the icaoperon for biofilm formation. Likely, they are commensal S. epidermidis strains but multi-antibiotic resistant. Uneven distribution of insertion sequences, phages, and CRISPR-Cas immunity phage systems suggest frequent horizontal gene transfer. Rates of recombination between S. epidermidis strains were more prevalent than the mutation rate and affected the whole genome. Therefore, the multidrug-resistance, independently of the pathogenic traits, might explain the persistence of specific highly adapted S. epidermidis clonal lineages in nosocomial settings.

scholarly journals Antibacterial Effects of Phage Lysin LysGH15 on Planktonic Cells and Biofilms of Diverse Staphylococci

2018 ◽  
Vol 84 (15) ◽  
Author(s):  
Yufeng Zhang ◽  
Mengjun Cheng ◽  
Hao Zhang ◽  
Jiaxin Dai ◽  
Zhimin Guo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Planktonic Cells ◽  
Content Type ◽  
Resistant Strains ◽  
Staphylococcus Hominis ◽  
Phage Lysin

ABSTRACT Treatment of infections caused by staphylococci has become more difficult because of the emergence of multidrug-resistant strains as well as biofilm formation. In this study, we observed the ability of the phage lysin LysGH15 to eliminate staphylococcal planktonic cells and biofilms formed by Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis. All these strains were sensitive to LysGH15, showing reductions in bacterial counts of approximately 4 log units within 30 min after treatment with 20 μg/ml of LysGH15, and the MICs ranged from 8 μg/ml to 32 μg/ml. LysGH15 efficiently prevented biofilm formation by the four staphylococcal species at a dose of 50 μg/ml. At a higher dose (100 μg/ml), LysGH15 also showed notable disrupting activity against 24-h and 72-h biofilms formed by S. aureus and coagulase-negative species. In the in vivo experiments, a single intraperitoneal injection of LysGH15 (20 μg/mouse) administered 1 h after the injection of S. epidermidis at double the minimum lethal dose was sufficient to protect the mice. The S. epidermidis cell counts were 4 log units lower in the blood and 3 log units lower in the organs of mice 24 h after treatment with LysGH15 than in the untreated control mice. LysGH15 reduced cytokine levels in the blood and improved pathological changes in the organs. The broad antistaphylococcal activity exerted by LysGH15 on planktonic cells and biofilms makes LysGH15 a valuable treatment option for biofilm-related or non-biofilm-related staphylococcal infections. IMPORTANCE Most staphylococcal species are major causes of health care- and community-associated infections. In particular, Staphylococcus aureus is a common and dangerous pathogen, and Staphylococcus epidermidis is a ubiquitous skin commensal and opportunistic pathogen. Treatment of infections caused by staphylococci has become more difficult because of the emergence of multidrug-resistant strains as well as biofilm formation. In this study, we found that all tested S. aureus, S. epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis strains were sensitive to the phage lysin LysGH15 (MICs ranging from 8 to 32 μg/ml). More importantly, LysGH15 not only prevented biofilm formation by these staphylococci but also disrupted 24-h and 72-h biofilms. Furthermore, the in vivo efficacy of LysGH15 was demonstrated in a mouse model of S. epidermidis bacteremia. Thus, LysGH15 exhibits therapeutic potential for treating biofilm-related or non-biofilm-related infections caused by diverse staphylococci.

Quantitative Analysis of Biofilm Formed on Vascular Prostheses by Staphylococcus Epidermidis with Different ica and aap Genetic Status

2013 ◽  
Vol 36 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Joanna Golus ◽  
Magdalena Stankevic ◽  
Rafal Sawicki ◽  
Renata Los ◽  
Anna Malm ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Fluorescence Microscopy ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Bacterial Colonization ◽  
Formation Mechanisms ◽  
Microscopy Imaging ◽  
Vascular Prostheses ◽  
Coverage Ratio ◽  
Genetic Status

Objectives This study aims to examine biofilm formed on vascular prostheses by Staphylococcus epidermidis with different ica and aap genetic status, and to evaluate the effect of antibiotic-modified prostheses on bacterial colonization. Methods Biofilm formation was determined using fluorescence microscopy imaging. Quantitative analysis was conducted using the biofilm coverage ratio (BCR) calculations. Results Our investigations prove that the BCR method with fluorescent dye enabled an accurate assessment of biofilm coverage and comparison of the obtained results. The ica+ aap+ strains formed a biofilm on all of the examined vascular prostheses. Uni-Graft® modified with covalently immobilized amikacin was effective in preventing bacterial adherence. Conclusions Molecular biology techniques combined with phenotype studies give a broad insight into biofilm formation mechanisms. On the other hand, fluorescence microscopy imaging along with BCR calculations are reliable and simple tools to quantitatively estimate biofilm formation, as well as the effectiveness of antimicrobial prosthesis modification.

scholarly journals Subinhibitory Concentrations of Mupirocin Stimulate Staphylococcus aureus Biofilm Formation by Upregulating cidA

2020 ◽  
Vol 64 (3) ◽  
Author(s):  
Ye Jin ◽  
Yinjuan Guo ◽  
Qing Zhan ◽  
Yongpeng Shang ◽  
Di Qu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Laser Scanning ◽  
Multidrug Resistant ◽  
Laser Scanning Microscopy ◽  
Extracellular Dna ◽  
Confocal Laser ◽  
Content Type ◽  
Subinhibitory Concentrations ◽  
Biofilm Development

ABSTRACT Previous studies have shown that the administration of antibiotics at subinhibitory concentrations stimulates biofilm formation by the majority of multidrug-resistant Staphylococcus aureus (MRSA) strains. Here, we investigated the effect of subinhibitory concentrations of mupirocin on biofilm formation by the community-associated (CA) mupirocin-sensitive MRSA strain USA300 and the highly mupirocin-resistant clinical S. aureus SA01 to SA05 isolates. We found that mupirocin increased the ability of MRSA cells to attach to surfaces and form biofilms. Confocal laser scanning microscopy (CLSM) demonstrated that mupirocin treatment promoted thicker biofilm formation, which also correlated with the production of extracellular DNA (eDNA). Furthermore, quantitative real-time PCR (RT-qPCR) results revealed that this effect was largely due to the involvement of holin-like and antiholin-like proteins (encoded by the cidA gene), which are responsible for modulating cell death and lysis during biofilm development. We found that cidA expression levels significantly increased by 6.05- to 35.52-fold (P < 0.01) after mupirocin administration. We generated a cidA-deficient mutant of the USA300 S. aureus strain. Exposure of the ΔcidA mutant to mupirocin did not result in thicker biofilm formation than that in the parent strain. We therefore hypothesize that the mupirocin-induced stimulation of S. aureus biofilm formation may involve the upregulation of cidA.

scholarly journals Role of the luxS Quorum-Sensing System in Biofilm Formation and Virulence of Staphylococcus epidermidis

2006 ◽  
Vol 74 (1) ◽  
pp. 488-496 ◽  
Author(s):  
Lin Xu ◽  
Hualin Li ◽  
Cuong Vuong ◽  
Viveka Vadyvaloo ◽  
Jianping Wang ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Mutant Strain ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Bacterial Pathogens ◽  
Sensing System ◽  
Autoinducer 2 ◽  
Enhanced Production ◽  
Quorum Sensing System ◽  
Biofilm Development

ABSTRACT Nosocomial infections caused by Staphylococcus epidermidis are characterized by biofilm formation on implanted medical devices. Quorum-sensing regulation plays a major role in the biofilm development of many bacterial pathogens. Here, we describe luxS, a quorum-sensing system in staphylococci that has a significant impact on biofilm development and virulence. We constructed an isogenic ΔluxS mutant strain of a biofilm-forming clinical isolate of S. epidermidis and demonstrated that luxS signaling is functional in S. epidermidis. The mutant strain showed increased biofilm formation in vitro and enhanced virulence in a rat model of biofilm-associated infection. Genetic complementation and addition of autoinducer 2-containing culture filtrate restored the wild-type phenotype, demonstrating that luxS repressed biofilm formation through a cell-cell signaling mechanism based on autoinducer 2 secretion. Enhanced production of the biofilm exopolysaccharide polysaccharide intercellular adhesin in the mutant strain is presumably the major cause of the observed phenotype. The agr quorum-sensing system has previously been shown to impact biofilm development and biofilm-associated infection in a way similar to that of luxS, although by regulation of different factors. Our study indicates a general scheme of quorum-sensing regulation of biofilm development in staphylococci, which contrasts with that observed in many other bacterial pathogens.

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