The two-component system ArlRS is essential for wall teichoic acid glycoswitching in .

is among the leading causes of hospital-acquired infections. Critical to biology and pathogenesis are the cell wall-anchored glycopolymers wall teichoic acids (WTA). Approximately one-third of isolates decorates WTA with a mixture of α1,4- and β1,4--acetylglucosamine (GlcNAc), which requires the dedicated glycosyltransferases TarM and TarS, respectively.

Forssman and the staphylococcal hemolysins.

Forssman was a Swedish pathologist and microbiologist who, in the 1920s and 1930s conducted a long series of experiments that led to unique insights into surface antigens of blood cells, as well as added to the discrimination of toxins produced by staphylococci that lyse red blood cells. This review takes offset in the studies published by Forssman in APMIS addressing the hemolytic properties of staphylococcal toxins displayed against erythrocytes of animal and human origin. In light of current knowledge, we will discuss the insights we now have and how they may pave the way for curing infections with pathogenic staphylococci, including Staphylococcus aureus.

A short-lived peptide signal regulates cell-to-cell communication in Listeria monocytogenes.

Quorum sensing (QS) is a mechanism that regulates group behavior in bacteria, and in Gram-positive bacteria, the communication molecules are often cyclic peptides, called autoinducing peptides (AIPs). We recently showed that pentameric thiolactone-containing AIPs from Listeria monocytogenes, and from other species, spontaneously undergo rapid rearrangement to homodetic cyclopeptides, which hampers our ability to study the activity of these short-lived compounds. Here, we developed chemically modified analogues that closely mimic the native AIPs while remaining structurally intact, by introducing N-methylation or thioester-to-thioether substitutions.

Staphylococcus aureus response and adaptation to vancomycin.

Antibiotic resistance is an increasing challenge for the human pathogen Staphylococcus aureus. Methicillin-resistant S. aureus (MRSA) clones have spread globally, and a growing number display decreased susceptibility to vancomycin, the favoured antibiotic for treatment of MRSA infections.

CI:Mor interactions in the lysogeny switches of TP901-1 and φ13 bacteriophages.

To structurally characterize in detail the interactions between the phage repressor (CI) and the antirepressor (Mor) in the lysis-lysogeny switches of two Gram-positive bacteriophages, the lactococcal TP901-1 and staphylococcal φ13. We use crystallographic structure determination, computational structural modeling, and analysis, as well as biochemical methods, to elucidate similarities and differences in the CI:Mor interactions for the two genetic switches. By comparing a newly determined and other available crystal structures for the N-terminal domain of CI (CI-NTD), we show that the CI interface involved in Mor binding undergoes structural changes upon binding in TP901-1.

mutants resistant to the feed-additive monensin show increased virulence and altered purine metabolism.

Ionophores are antibacterial compounds that affect bacterial growth by changing intracellular concentrations of the essential cations, sodium and potassium. They are extensively used in animal husbandry to increase productivity and reduce infectious diseases, but our understanding of the potential for and effects of resistance development to ionophores is poorly known. Thus, given their widespread global usage, it is important to determine the potential negative consequences of ionophore use on human and animal health.

Cross-species communication via agr controls phage susceptibility in Staphylococcus aureus.

Bacteria use quorum sensing (QS) to coordinate group behavior in response to cell density, and some bacterial viruses (phages) also respond to QS. In Staphylococcus aureus, the agr-encoded QS system relies on accumulation of auto-inducing cyclic peptides (AIPs). Other staphylococci also produce AIPs of which many inhibit S.

Evolutionary history of Staphylococcus aureus influences antibiotic resistance evolution.

Antibiotic resistance often confers a fitness cost to the resistant cell and thus raises key questions of how resistance is maintained in the absence of antibiotics and, if lost, whether cells are genetically primed for re-evolving resistance. To address these questions, we have examined vancomycin-intermediate Staphylococcus aureus (VISA) strains that arise during vancomycin therapy. VISA strains harbor a broad spectrum of mutations, and they are known to be unstable both in patients and in the laboratory.

Fluoroquinolone resistance does not facilitate phage Φ13 integration or excision in .

Prophages of the ΦSa3int family are commonly found in human-associated strains of where they encode factors for evading the human innate immune system. In contrast, they are usually absent in livestock-associated methicillin-resistant (LA-MRSA) strains where the phage attachment site is mutated compared to the human strains. However, ΦSa3int phages have been found in a subset of LA-MRSA strains belonging to clonal complex 398 (CC398), including a lineage that is widespread in pig farms in Northern Jutland, Denmark.

An Endogenous Staphylococcus aureus CRISPR-Cas System Limits Phage Proliferation and Is Efficiently Excised from the Genome as Part of the SCC Cassette.

CRISPR-Cas is an adaptive immune system that allows bacteria to inactivate mobile genetic elements. Approximately 50% of bacteria harbor CRISPR-Cas; however, in the human pathogen Staphylococcus aureus, CRISPR-Cas loci are less common and often studied in heterologous systems. We analyzed the prevalence of CRISPR-Cas in genomes of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated in Denmark.

Assessment of human exposure risk related to contamination of Danish sow carcasses with bile containing Salmonella.

In 2020, the Danish competent authority (CA) raised questions about the Salmonella exposure risk to consumers from bile-contaminated pig carcasses. This study assesses this risk related to sow carcasses. A total of 300 bile samples were collected aseptically at a large Danish sow abattoir.

Polyether Ionophore Antibiotics Target Drug-Resistant Clinical Isolates, Persister Cells, and Biofilms.

Polyether ionophores are complex natural products known to transport various cations across biological membranes. While several members of this family are used in agriculture (e.g.

Intrinsic (L) sub-class in and is associated with a reduced susceptibility toward tetracycline.

Annotations of non-pathogenic bacterial genomes commonly reveal putative antibiotic resistance genes and the potential risks associated with such genes is challenging to assess. We have examined a putative tetracycline (L) gene (conferring low level tetracycline resistance), present in the majority of all publicly available genomes of the industrially important operational group including the species and . The aim was to examine the risk of transfer of the putative (L) in operational group through phylogenetic and genomic position analysis.

Adaptive laboratory evolution and independent component analysis disentangle complex vancomycin adaptation trajectories.

Human infections with methicillin-resistant (MRSA) are commonly treated with vancomycin, and strains with decreased susceptibility, designated as vancomycin-intermediate (VISA), are associated with treatment failure. Here, we profiled the phenotypic, mutational, and transcriptional landscape of 10 VISA strains adapted by laboratory evolution from one common MRSA ancestor, the USA300 strain JE2. Using functional and independent component analysis, we found that: 1) despite the common genetic background and environmental conditions, the mutational landscape diverged between evolved strains and included mutations previously associated with vancomycin resistance (in , , , , and ) as well as novel adaptive mutations (SAUSA300_RS04225, , , and ); 2) the first wave of mutations affected transcriptional regulators and the second affected genes involved in membrane biosynthesis; 3) expression profiles were predominantly strain-specific except for and , which were the only two genes significantly differentially expressed in all clones; 4) three independent virulence systems (φSa3, SaeR, and T7SS) featured as the most transcriptionally perturbed gene sets across clones; 5) there was a striking variation in oxacillin susceptibility across the evolved lineages (from a 10-fold increase to a 63-fold decrease) that also arose in clinical MRSA isolates exposed to vancomycin and correlated with susceptibility to teichoic acid inhibitors; and 6) constitutive expression of the VraR regulon explained cross-susceptibility, while mutations in were associated with cross-resistance.

Finding New Fundamental Pieces for the Bacterial Cell Division Puzzle.

The division of bacterial cells into two daughter cells requires a precise balance of more than a dozen highly conserved proteins that coordinate chromosome segregation with the synthesis of the novel cell envelope. The paradigms of cell division were established in rod-shaped bacteria and this fundamental process is far less characterized in spherical bacteria. In a search for novel, essential cell division proteins in Staphylococci, Myrbråten et al.

Soluble C-Type Lectin-Receptor Ligands Stimulate ROS Production in Dendritic Cells and Potentiate Killing of MRSA as Well as the MRSA Induced IL-12 Production.

Methicillin resistant (MRSA) has developed resistance to most β-lactam antibiotics leaving few treatment options against infections with MRSA. Through mannose receptors, mannan potentiates IL-12 production induced by Gram-positive bacteria, a cytokine crucial in the clearance of infection. We investigated the IL-12 potentiating effect of mannan pre-treatment of bone marrow-derived dendritic cells prior to stimulation with clinical MRSA strains.

Survival of hospital- and community-associated Enterococcus faecium following exposure to in-use concentrations of the biocide sodium dichloroisocyanurate (NaDCC).

Objectives: Hospital-associated infections with vancomycin-resistant Enterococcus faecium (VREfm) have increased dramatically in Denmark. A cornerstone in infection control is effective cleaning and disinfection. This study investigated the survival and resuscitation/growth of clinical isolates of E.

Screening for Highly Transduced Genes in Staphylococcus aureus Revealed Both Lateral and Specialized Transduction.

Bacteriophage-mediated transduction of bacterial DNA is a major route of horizontal gene transfer in the human pathogen, Staphylococcus aureus. Transduction involves the packaging of bacterial DNA by viruses and enables the transmission of virulence and resistance genes between cells. To learn more about transduction in S.

Targeting the ATP synthase in bacterial and fungal pathogens: beyond Mycobacterium tuberculosis.

The ATP synthase is a multicomponent enzyme that is largely conserved across the kingdoms of life. In many species the ATP synthase is central in the synthesis of ATP by using the electrochemical proton gradient generated via the electron transport chain. Bacteria inhabit very diverse ecological niches; hence their metabolism to extract nutrients and generation of ATP varies from species to species.

The menaquinone pathway is important for susceptibility of Staphylococcus aureus to the antibiotic adjuvant, cannabidiol.

Emergence of antibiotic resistant bacteria is evolving at an alarming pace; therefore, we must start turning to alternative approaches. One of these, could be the use of antibiotic adjuvants that enhances the effect of antibiotics towards resistant bacteria. A novel antibiotic adjuvant is cannabidiol (CBD), which we have previously shown can enhance the effect of bacitracin (BAC).

Spontaneous Phage Resistance in Avian Pathogenic .

Avian pathogenic (APEC) is one of the most important bacterial pathogens affecting poultry worldwide. The emergence of multidrug-resistant pathogens has renewed the interest in the therapeutic use of bacteriophages (phages). However, a major concern for the successful implementation of phage therapy is the emergence of phage-resistant mutants.

Classification of In Vitro Phage-Host Population Growth Dynamics.

The therapeutic use of bacteriophages (phage therapy) represents a promising alternative to antibiotics to control bacterial pathogens. However, the understanding of the phage-bacterium interactions and population dynamics seems essential for successful phage therapy implementation. Here, we investigated the effect of three factors: phage species (18 lytic -infecting phages); bacterial strain (10 APEC strains); and multiplicity of infection (MOI) (MOI 10, 1, and 0.

Staphylococcal Phages Adapt to New Hosts by Extensive Attachment Site Variability.

Bacterial pathogens commonly carry prophages that express virulence factors, and human strains of Staphylococcus aureus carry Sa3int phages, which promote immune evasion. Recently, however, these phages have been found in livestock-associated, methicillin-resistant S. aureus (LA-MRSA).

Characterization of the genetic switch from phage ɸ13 important for Staphylococcus aureus colonization in humans.

Temperate phages are bacterial viruses that after infection either reside integrated into a bacterial genome as prophages forming lysogens or multiply in a lytic lifecycle. The decision between lifestyles is determined by a switch involving a phage-encoded repressor, CI, and a promoter region from which lytic and lysogenic genes are divergently transcribed. Here, we investigate the switch of phage ɸ13 from the human pathogen Staphylococcus aureus.