Proteomics uncovers extreme heterogeneity in the <i>Staphylococcus aureus</i> exoproteome due to genomic plasticity and variant gene regulation

Ziebandt, Anne-Kathrin; Kusch, Harald; Degner, Marco; Jaglitz, Sarah; Sibbald, Mark J. J. B.; Arends, Jan P.; Chlebowicz, Monika A.; Albrecht, Dirk; Pantůček, Roman; Doškař, Jiřı́; Ziebuhr, Wilma; Bröker, Barbara M.; Hecker, Michael; Dijl, Jan Maarten van; Engelmann, Susanne

doi:10.1002/pmic.200900313

Cited by 137 publications

(149 citation statements)

References 52 publications

Supporting

Mentioning

142

Contrasting

Order By: Relevance

“…However, a note of caution is in place, since the genome sequence does as yet neither allow an accurate prediction of the potentially conditional expression of particular genes, nor their expression level. This is critically underscored by proteomics studies on the cell surface and exoproteomes of different isolates of S. aureus, which revealed high degrees of variation in the expression of particular proteins, including known virulence factors [100][101][102]. Lastly, genome sequences will be also used to search for genetic markers, such as the presence or absence of a gene or an amino acid substitution in a protein, which can then be linked with an exclusive or higher occurrence in a disease, or associated with disease severity and virulence.…”

Section: Whole Genome Sequencingmentioning

confidence: 99%

Overview of molecular typing methods for outbreak detection and epidemiological surveillance

et al. 2013

View full text Add to dashboard Cite

Typing methods for discriminating different bacterial isolates of the same species are essential epidemiological tools in infection prevention and control. Traditional typing systems based on phenotypes, such as serotype, biotype, phage-type, or antibiogram, have been used for many years. However, more recent methods that examine the relatedness of isolates at a molecular level have revolutionised our ability to differentiate among bacterial types and subtypes. Importantly, the development of molecular methods has provided new tools for enhanced surveillance and outbreak detection. This has resulted in better implementation of rational infection control programmes and efficient allocation of resources across Europe. The emergence of benchtop sequencers using next generation sequencing technology makes bacterial whole genome sequencing (WGS) feasible even in small research and clinical laboratories. WGS has already been used for the characterisation of bacterial isolates in several large outbreaks in Europe and, in the near future, is likely to replace currently used typing methodologies due to its ultimate resolution. However, WGS is still too laborious and time-consuming to obtain useful data in routine surveillance. Also, a largely unresolved question is how genome sequences must be examined for epidemiological characterisation. In the coming years, the lessons learnt from currently used molecular methods will allow us to condense the WGS data into epidemiologically useful information. On this basis, we have reviewed current and new molecular typing methods for outbreak detection and epidemiological surveillance of bacterial pathogens in clinical practice, aiming to give an overview of their specific advantages and disadvantages.

show abstract

Section: Whole Genome Sequencingmentioning

confidence: 99%

Overview of molecular typing methods for outbreak detection and epidemiological surveillance

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Intriguingly, recent proteomics studies have revealed an enormous diversity in the production of virulence factors by different isolates of S. aureus, and only a few of these seem to be invariantly produced (3)(4)(5). Among the most commonly identified staphylococcal virulence factors, especially in the community-associated (CA)-MRSA lineages, are the so-called phenol-soluble modulins (PSMs) (6).…”

Section: S Taphylococcus Aureus Is An Opportunistic Human Pathogen Thatmentioning

confidence: 99%

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

Tsompanidou

Denham

Becher

et al. 2013

Appl Environ Microbiol

Self Cite

View full text Add to dashboard Cite

The human pathogen Staphylococcus aureus is renowned for the rapid colonization of contaminated wounds, medical implants, and food products. Nevertheless, little is known about the mechanisms that allow S. aureus to colonize the respective wet surfaces. The present studies were therefore aimed at identifying factors used by S. aureus cells to spread over wet surfaces, starting either from planktonic or biofilm-associated states. Through proteomics analyses we pinpoint phenol-soluble modulins (PSMs) as prime facilitators of the spreading process. To dissect the roles of the eight PSMs produced by S. aureus, these peptides were chemically synthesized and tested in spreading assays with different psm mutant strains. The results show that PSM␣3 and PSM␥ are the strongest facilitators of spreading both for planktonic cells and cells in catheter-associated biofilms. Compared to the six other PSMs of S. aureus, PSM␣3 and PSM␥ combine strong surfactant activities with a relatively low overall hydropathicity. Importantly, we show that PSM-mediated motility of S. aureus facilitates the rapid colonization of wet surfaces next to catheters and the colonization of fresh meat. S taphylococcus aureus is an opportunistic human pathogen thatcan cause a wide range of acute and chronic diseases, which range from superficial skin infections to life-threatening endocarditis and sepsis (1, 2). The ability of this Gram-positive bacterium to cause these infections depends on the production of secreted and cell wall-associated virulence factors. Of increasing concern is the ability of S. aureus to acquire resistance against antibiotics, as underscored by the global spread of methicillin-resistant S. aureus (MRSA) lineages.Intriguingly, recent proteomics studies have revealed an enormous diversity in the production of virulence factors by different isolates of S. aureus, and only a few of these seem to be invariantly produced (3-5). Among the most commonly identified staphylococcal virulence factors, especially in the community-associated (CA)-MRSA lineages, are the so-called phenol-soluble modulins (PSMs) (6). These PSMs are short, amphipathic, ␣-helical peptides that have leukocidal activity and biosurfactant properties (7-9). The growth media of S. aureus cultures contain both N-terminally formylated and deformylated PSMs, suggesting that these virulence factors are substrates for the bacterial N-formylmethionine deformylase (9, 10).To date, eight PSMs have been identified in S. aureus. These include the four PSM␣1 to PSM␣4 peptides (22 residues each), the PSM␤1 and PSM␤2 peptides (44 residues each), PSM␥ (25 residues) and the recently reported PSM-mec (22 residues). The PSM␣ peptides are encoded by the psm␣ operon, the PSM␤ peptides by the psm␤ operon, and PSM␥ by the hld gene. Notably, the hld gene is embedded within the regulatory RNAIII molecule that is encoded by the agr locus. The gene for PSM-mec was identified in MRSA strains carrying the staphylococcal cassette chromosome mec (SCCmec) types II or III. The expression of all ps...

show abstract

“…For example, AtlA lysibody and ClyS lysibody bound all strains of S. aureus tested as well as several coagulase-negative staphylococci, whereas PlySs2 lysibody bound streptococci and enterococci in addition to staphylococci. The protein targets of monoclonal antibodies, on the other hand, are often variable even at the species level and may not always be expressed (44)(45)(46)(47). This may limit the strain coverage of certain monoclonal antibodies and could also result in the selection of escape mutants during the course of treatment.…”

Section: Discussionmentioning

confidence: 99%

Lysibodies are IgG Fc fusions with lysin binding domains targetingStaphylococcus aureuswall carbohydrates for effective phagocytosis

Raz

Serrano

Lawson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The cell wall of Gram-positive bacteria contains abundant surfaceexposed carbohydrate molecules that are highly conserved within and often across species. The potential therapeutic usefulness of high-affinity antibodies to cell wall carbohydrates is unquestioned, however obtaining such antibodies is challenging due to the poor overall immunogenicity of these bacterial targets. Autolysins and phage lysins are peptidoglycan hydrolases, enzymes that have evolved over a billion years to degrade bacterial cell wall. Such wall hydrolases are modular enzymes, composed of discrete domains for high-affinity binding to cell wall carbohydrates and cleavage activity. In this study, we demonstrate that binding domains from autolysins and lysins can be fused to the Fc region of human IgG, creating a fully functional homodimer (or "lysibody") with high-affinity binding and specificity for carbohydrate determinants on the bacterial surface. Furthermore, we demonstrate that this process is reproducible with three different binding domains specific to methicillin-resistant Staphylococcus aureus (MRSA). Cell-bound lysibodies induced the fixation of complement on the bacterial surface, promoted phagocytosis by macrophages and neutrophils, and protected mice from MRSA infection in two model systems. The lysibody approach could be used to target a range of difficult-to-treat pathogenic bacteria, given that cell wall hydrolases are ubiquitous in nature.immunotherapy | antibody | vaccine | monoclonal | peptidoglycan hydrolase

show abstract

Proteomics uncovers extreme heterogeneity in the Staphylococcus aureus exoproteome due to genomic plasticity and variant gene regulation

Cited by 137 publications

References 52 publications

Overview of molecular typing methods for outbreak detection and epidemiological surveillance

Overview of molecular typing methods for outbreak detection and epidemiological surveillance

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

Lysibodies are IgG Fc fusions with lysin binding domains targetingStaphylococcus aureuswall carbohydrates for effective phagocytosis

Contact Info

Product

Resources

About