delta toxin modulates both extracellular membrane vesicle biogenesis and amyloid formation.

Extracellular membrane vesicles (MVs) produced by in planktonic cultures encapsulate a diverse cargo of bacterial proteins, nucleic acids, and glycopolymers that are protected from destruction by external factors. δ-toxin, a member of the phenol soluble modulin family, was shown to be critical for MV biogenesis. Amyloid fibrils co-purified with MVs generated by virulent, community-acquired strains, and fibril formation was dependent on expression of the δ-toxin gene ().

Delta Toxin Modulates both Extracellular Membrane Vesicle Biogenesis and Amyloid Formation.

Unlabelled: secretes phenol-soluble modulins (PSMs), a family of small, amphipathic, secreted peptides with multiple biologic activities. Community-acquired strains produce high levels of PSMs in planktonic cultures, and PSM alpha peptides have been shown to augment the release of extracellular membrane vesicles (MVs). We observed that amyloids, aggregates of proteins characterized by a fibrillar morphology and stained with specific dyes, co-purified with MVs harvested from cell-free culture supernatants of community-acquired strains.

Two transporters cooperate to secrete amphipathic peptides from the cytoplasmic and membranous milieus.

Diverse organisms secrete amphipathic biomolecules for competitive gains. However, how cells cope with producing these membrane-permeabilizing molecules is unclear. We focused on the PSM family of secreted amphipathic peptides in the pathogen that uses two ABC transporters, PmtCD and AbcA, to export peptides across the bacterial cell membrane.

Essential role of membrane vesicles for biological activity of the bacteriocin micrococcin P1.

Bacterial membrane vesicles (MVs) have recently gained much attention and have been shown to carry a wide diversity of secreted bacterial components. However, it is poorly understood whether MV carriage is an indispensable requirement for a cargo's function. Bacteriocins as weapons of bacterial warfare shape the composition of microbial communities.

Corynebacterium pseudodiphtheriticum Exploits Staphylococcus aureus Virulence Components in a Novel Polymicrobial Defense Strategy.

Commensal bacteria in the human nasal cavity are known to suppress opportunistic pathogen colonization by competing for limited space and nutrients. It has become increasingly apparent that some commensal bacteria also produce toxic compounds that directly inhibit or kill incoming competitors. Numerous studies suggest that microbial species-specific interactions can affect human nasal colonization by the opportunistic pathogen However, the complex and dynamic molecular interactions that mediate these effects on nasal colonization are often difficult to study and remain poorly understood.

Antimicrobial Peptide Resistance Mechanism Contributes to Staphylococcus aureus Infection.

Antimicrobial peptides (AMPs) constitute an important part of innate host defense. Possibly limiting the therapeutic potential of AMPs is the fact that bacteria have developed AMP resistance mechanisms during their co-evolution with humans. However, there is no direct evidence that AMP resistance per se is important during an infection.

Lipoyl-E2-PDH Gets a Second Job.

Pyruvate dehydrogenase (PDH) plays a well-known metabolic role inside cells. In this issue of Cell Host & Microbe, Grayczyk et al. (2017) show that the bacterial pathogen Staphylococcus aureus unexpectedly secretes and repurposes the lipoylated E2 subunit of PDH to suppress TLR-mediated activation of host macrophages by bacterial lipoproteins.

Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance.

The rapid evolution and dissemination of antibiotic resistance among bacterial pathogens are outpacing the development of new antibiotics, but antivirulence agents provide an alternative. These agents can circumvent antibiotic resistance by disarming pathogens of virulence factors that facilitate human disease while leaving bacterial growth pathways - the target of traditional antibiotics - intact. Either as stand-alone medications or together with antibiotics, these drugs are intended to treat bacterial infections in a largely pathogen-specific manner.

Mechanism of Gene Regulation by a Staphylococcus aureus Toxin.

Unlabelled: The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves.

Crystal Structures and Inhibition Kinetics Reveal a Two-Stage Catalytic Mechanism with Drug Design Implications for Rhomboid Proteolysis.

Intramembrane proteases signal by releasing proteins from the membrane, but despite their importance, their enzymatic mechanisms remain obscure. We probed rhomboid proteases with reversible, mechanism-based inhibitors that allow precise kinetic analysis and faithfully mimic the transition state structurally. Unexpectedly, inhibition by peptide aldehydes is non-competitive, revealing that in the Michaelis complex, substrate does not contact the catalytic center.

The rhomboid protease family: a decade of progress on function and mechanism.

Rhomboid proteases are the largest family of enzymes that hydrolyze peptide bonds within the cell membrane. Although discovered to be serine proteases only a decade ago, rhomboid proteases are already considered to be the best understood intramembrane proteases. The presence of rhomboid proteins in all domains of life emphasizes their importance but makes their evolutionary history difficult to chart with confidence.

Evidence for bidentate substrate binding as the basis for the K48 linkage specificity of otubain 1.

Otubain 1 belongs to the ovarian tumor (OTU) domain class of cysteine protease deubiquitinating enzymes. We show here that human otubain 1 (hOtu1) is highly linkage-specific, cleaving Lys48 (K48)-linked polyubiquitin but not K63-, K29-, K6-, or K11-linked polyubiquitin, or linear alpha-linked polyubiquitin. Cleavage is not limited to either end of a polyubiquitin chain, and both free and substrate-linked polyubiquitin are disassembled.

Dissociation of the carbohydrate-binding and splicing activities of galectin-1.

Galectin-1 (Gal1) and galectin-3 (Gal3) are two members of a family of carbohydrate-binding proteins that are found in the nucleus and that participate in pre-mRNA splicing assayed in a cell-free system. When nuclear extracts (NE) of HeLa cells were subjected to adsorption on a fusion protein containing glutathione S-transferase (GST) and Gal3, the general transcription factor II-I (TFII-I) was identified by mass spectrometry as one of the polypeptides specifically bound. Lactose and other saccharide ligands of the galectins inhibited GST-Gal3 pull-down of TFII-I while non-binding carbohydrates failed to yield the same effect.