Carbohydrate and Lipid-Containing Elicitors from Phytophthora infestans. Do They Have a Common Mechanism of Action?

P128 is an anti-staphylococcal protein consisting of the Staphylococcus aureus phage-K-derived tail-associated muralytic enzyme (TAME) catalytic domain (Lys16) fused with the cell-wall-binding SH3b domain of lysostaphin. In order to understand the mechanism of action and emergence of resistance to P128, we isolated mutants of Staphylococcus spp., including meticillin-resistant Staphylococcus aureus (MRSA), resistant to P128. In addition to P128, the mutants also showed resistance to Lys16, the catalytic domain of P128. The mutants showed loss of fitness as shown by reduced rate of growth in vitro. One of the mutants tested was found to show reduced virulence in animal models of S. aureus septicaemia suggesting loss of fitness in vivo as well. Analysis of the antibiotic sensitivity pattern showed that the mutants derived from MRSA strains had become sensitive to meticillin and other β-lactams. Interestingly, the mutant cells were resistant to the lytic action of phage K, although the phage was able to adsorb to these cells. Sequencing of the femA gene of three P128-resistant mutants showed either a truncation or deletion in femA, suggesting that improper cross-bridge formation in S. aureus could be causing resistance to P128. Using glutathione S-transferase (GST) fusion peptides as substrates it was found that both P128 and Lys16 were capable of cleaving a pentaglycine sequence, suggesting that P128 might be killing S. aureus by cleaving the pentaglycine cross-bridge of peptidoglycan. Moreover, peptides corresponding to the reported cross-bridge of Staphylococcus haemolyticus (GGSGG, AGSGG), which were not cleaved by lysostaphin, were cleaved efficiently by P128. This was also reflected in high sensitivity of S. haemolyticus to P128. This showed that in spite of sharing a common mechanism of action with lysostaphin, P128 has unique properties, which allow it to act on certain lysostaphin-resistant Staphylococcus strains.

Download Full-text

Diacylglycerol ‐induced suppression of vascular KCNQ channels ‐A common mechanism of action of vasoconstrictor hormones?

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.579.1 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Bharath Mani ◽

Lioubov Brueggemann ◽

Kenneth Byron

Keyword(s):

Mechanism Of Action ◽

Common Mechanism ◽

Kcnq Channels

Download Full-text

Refining a great idea: the consolidation of PECS I, PECS II and serratus blocks into a single thoracic fascial plane block, the SAP block

Regional Anesthesia and Pain Medicine ◽

10.1136/rapm-2019-100745 ◽

2019 ◽

pp. rapm-2019-100745 ◽

Cited By ~ 2

Author(s):

Carlo D Franco ◽

Konstantin Inozemtsev

Keyword(s):

Brachial Plexus ◽

Chest Wall ◽

Mechanism Of Action ◽

Sensory Innervation ◽

Common Mechanism ◽

Nerve Blocks ◽

Intercostal Nerves ◽

Lateral Branches ◽

Fascial Plane Block ◽

Fascial Plane

The popularity of ultrasound-guided nerve blocks has impacted the practice of regional anesthesia in profound ways, improving some techniques and introducing new ones. Some of these new nerve blocks are based on the concept of fascial plane blocks, in which the local anesthetic is injected into a plane instead of around a specific nerve. Pectoralis muscles (PECS) and serratus blocks, most commonly used for post op analgesia after breast surgery, are good examples. Among the nerves targeted by PECS/serratus blocks are different branches of the brachial plexus that traditionally have been considered purely motor nerves. This unsubstantiated claim is a departure from accepted anatomical knowledge and challenges our understanding of the sensory innervation of the chest wall. The objective of this Daring Discourse is to look beyond the ability of PECS/serratus blocks to provide analgesia/anesthesia of the chest wall, to concentrate instead on understanding the mechanism of action of these blocks and, in the process, test the veracity of the claim. After a comprehensive review of the evidence we have concluded that (1) the traditional model of sensory innervation of the chest wall, which derives from the lateral branches of the upper intercostal nerves and does not include branches of the brachial plexus, is correct. (2) PECS/serratus blocks share the same mechanism of action, blocking the lateral branches of the upper intercostal nerves, and so their varied success is tied to their ability to reach them. This common mechanism agrees with the traditional innervation model. (3) A common mechanism of action supports the consolidation of PECS/serratus blocks into a single thoracic fascial plane block with a point of injection closer to the effector site. In a nod to transversus abdominus plane block, the original inspiration for PECS blocks, we propose naming this modified block, the serratus anterior plane block.

Download Full-text