Comparative mass spectrometry-based metabolomics strategies for the investigation of microbial secondary metabolites.

Members of the Staphylococcus aureus phenol-soluble modulin (PSM) peptide family are secreted as functional amyloids that serve diverse roles in pathogenicity and may be present as full-length peptides or as naturally occurring truncations. We recently showed that the activity of PSMα3, the most toxic member, stems from the formation of cross-α fibrils, which are at variance with the cross-β fibrils linked with eukaryotic amyloid pathologies. Here, we show that PSMα1 and PSMα4, involved in biofilm structuring, form canonical cross-β amyloid fibrils wherein β-sheets tightly mate through steric zipper interfaces, conferring high stability. Contrastingly, a truncated PSMα3 has antibacterial activity, forms reversible fibrils, and reveals two polymorphic and atypical β-rich fibril architectures. These architectures are radically different from both the cross-α fibrils formed by full-length PSMα3, and from the canonical cross-β fibrils. Our results point to structural plasticity being at the basis of the functional diversity exhibited by S. aureus PSMαs.

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Extreme amyloid polymorphism in Staphylococcus aureus virulent PSMα peptides.

The ability of bacteria to move is critical for their survival in diverse environments and multiple ways have evolved to achieve this. Two forms of motility have recently been described for Staphylococcus aureus, an organism previously considered to be non-motile. One form is called spreading, which is a type of sliding motility and the second form involves comet formation, which has many observable characteristics associated with gliding motility. Darting motility has also been observed in Staphylococcus epidermidis. This review describes how motility is defined and how we distinguish between passive and active motility. We discuss the characteristics of the various forms of Staphylococci motility, the molecular mechanisms involved and the potential future research directions.

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Defining motility in the Staphylococci.

Natural products as mediators of disease

Staphylococcus aureus is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis. S. aureus has a high level of antibiotic resistance and is a common cause of infections in hospitals and the community. The rising prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA), combined with the important severity of S. aureus infections in general, has resulted in the frequent use of anti-staphylococcal antibiotics, leading to increasing resistance rates. Antibiotic-resistant S. aureus continues to be a major health concern, necessitating the development of novel therapeutic strategies. S. aureus uses a wide range of virulence factors, such as toxins, to develop an infection in the host. Recently, anti-virulence treatments that directly or indirectly neutralize S. aureus toxins have showed promise. In this review, we provide an update on toxin pathogenic characteristics, as well as anti-toxin therapeutical strategies.

Staphylococcus aureus Toxins: An Update on Their Pathogenic Properties and Potential Treatments.

Phenol Soluble Modulin (PSM) Variants of Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) Captured Using Mass Spectrometry-Based Molecular Networking

The reaction of potassium (aza-15-crown-5)dithiocarbamate (KO4NCS2) and (Me2S)AuCl gave the dinuclear complex [Au(O4NCS2)]2, which underwent structural transformation upon heating to rearrange into the hexanuclear complex [Au(O4NCS2)]6. Under similar reaction conditions, KO4NCS2 reacted with AgNO3 or [Cu(CH3CN)4]ClO4 to give the 1-D coordination polymer [Ag(O4NCS2)]n (1) and the tetranuclear complex [Cu(O4NCS2)]4 (2), respectively. It is noted that upon heating a similar structural transformation process occurs from tetranuclear complex 2 to the octanuclear complex [Cu(O4NCS2)]8 (2'), connected by a weak Cu⋯S contact of 2.846 Å, and it has been isolated and corroborated by powder and single-crystal X-ray diffraction studies as well. Moreover, a variety of MO4NCS2 salts (M = Li+, Na+, K+ and Rb+) were used to react with AgNO3 to construct a series of coordination architectures: [LiAg(O4NCS2)2(μ-H2O)0.5]2 (3), {Na[Ag(O4NCS2)2]}n (4), {K[Ag(O4NCS2)2]}n (5) and {Rb[Ag(O4NCS2)2]}n (6). The smallest Li+ ion only coordinates with four oxygen atoms from the same azacrown ether ring and one H2O molecule, leading to a 1-D hydrogen-bonded chain with another azacrown ether ring for complex 3. The larger Na+ ion coordinates with seven oxygen atoms from two different crown ether rings, leading to a 1-D chain for complex 4. However, the largest K+ and Rb+ ions constitute a 1-D framework, except that each metal ion coordinates with eight oxygen atoms from two different crown ether rings, featuring a 1-D helical chain for complexes 5 and 6. Hence, the different sizes of alkaline metal ions exert a dramatic effect on the structural motifs of complexes 3-6. Remarkably, the dithiocarbamate moieties adopt μ2-bridging ([Au(O4NCS2)]2 and [Au(O4NCS2)]6), μ3- and μ4-bridging (1-2) and chelate forms (3-6) in the structural backbones.

Jun Hung

Papers

Phenol Soluble Modulin (PSM) Variants of Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) Captured Using Mass Spectrometry-Based Molecular Networking

Supramolecular assembly and structural transformation of d10-metal complexes containing (aza-15-crown-5)dithiocarbamate.