Monday, September 22, 2014

Staphylococcus Paradox


      "Staphylococcus aureus" or more commonly known as "The Staph", is a gram positive cocci in clusters, famous everywhere in the world for a subtype called as MRSA. It has been a really long time since i have blogged something about this organism. Perhaps this is the right time for me to get back talking about this paper.

    One of the most common infections caused by S aureus is skin infections, with an array of virulence factors involved. There are defense systems mounted on the skin, one of which is free fatty acids. The presence of these bactericidal compounds makes it less hospitable for the organisms such as staphylococcus. Obviously, staphylococcus has evolved counter defense mechanisms. But here is the catch of the question. There is a key enzyme called as SAL-2 which basically breaks down the lipid component of skin, producing high concentrations of fatty acids that inhibited bacterial growth. That seems to defy common sense. Bacteria produces an enzyme to produce a compound that will inhibits its own growth!!! As the authors say , “But in the case of the wildtype, the activity of SAL2 lipase produced high concentrations of fatty acids that inhibited bacterial growth”

      MRSA PFGE strain type USA300 (Or commonly known as USA300 strain) is a CA- MRSA subtype representing hypervirulence first reported in the USA as a cause of skin and soft issue infection in 2000. Genetically it is MLST type 8, clonal complex 8 with SccMec IV. The importance is that this strain is highly adapted to living in the skin. Several genetic factors have been proposed to have a role such as speG which induces tolerance to polyamines in the skin. This is further amplified by the fact that SAL-2 is highly conserved and detectable across S aureus.

       Quote from investigator, "In previous work, SAL-2 was identified as one of just seven secreted proteins that was universally produced by 63 diverse strains of S aureus and, as such, it is unlikely that S. aureus would have evolved to maintain abundant production of SAL2 if it did not confer a substantial benefit to the bacterium". Source

       SAL (Staphylococcus aureus lipase), comes in multiple forms, SAL-1, SAL-2 and SAL-3. SAL-2 is known to be derived into staphylococcus through a bacteriophage (Φ29 like phage, member of podoviridae) called SAP-2. Biochemical studies have shown that in its purified form it has a specific activity against S aureus cell wall with a MIC of 1μg/ml.

     So now you see the contrast. SAL-2 is inhibitory yet it is being carried almost universally and helps in virulence. In the new paper by Heinrichs etal; the paradox was studied by engineering strains of CA-MRSA that could not make SAL2 lipase, and compared the mutant and the wild-type responses to triglycerides. Result, mutants grew well in the presence of triglycerides. The basic findings were that SAL-2 is processed to active form by Aureolysin. The active form hydrolyzes triglycerides of both short and long chain fatty acids. SAL2 hydrolyzes trilinolein to linoleic acid, a fatty acid with known anti-staphylococcal properties.

      The paper has presented with the same challenge that initially was in question. However, it is clear that the SAL-2 is inhibitory, yet consistently carried and helps in better colonization. More studies are needed to elucidate the paradox.
Planet PJ, LaRussa SJ, Dana A, Smith H, Xu A, Ryan C, Uhlemann AC, Boundy S, Goldberg J, Narechania A, Kulkarni R, Ratner AJ, Geoghegan JA, Kolokotronis SO, & Prince A (2013). Emergence of the epidemic methicillin-resistant Staphylococcus aureus strain USA300 coincides with horizontal transfer of the arginine catabolic mobile element and speG-mediated adaptations for survival on skin. mBio, 4 (6) PMID: 24345744

Ziebandt AK, Kusch H, Degner M, Jaglitz S, Sibbald MJ, Arends JP, Chlebowicz MA, Albrecht D, Pantucek R, Doskar J, Ziebuhr W, Bröker BM, Hecker M, van Dijl JM, & Engelmann S (2010). Proteomics uncovers extreme heterogeneity in the Staphylococcus aureus exoproteome due to genomic plasticity and variant gene regulation. Proteomics, 10 (8), 1634-44 PMID: 20186749

Son JS, Lee SJ, Jun SY, Yoon SJ, Kang SH, Paik HR, Kang JO, & Choi YJ (2010). Antibacterial and biofilm removal activity of a podoviridae Staphylococcus aureus bacteriophage SAP-2 and a derived recombinant cell-wall-degrading enzyme. Applied microbiology and biotechnology, 86 (5), 1439-49 PMID: 20013118

Cadieux B, Vijayakumaran V, Bernards MA, McGavin MJ, & Heinrichs DE (2014). Role of lipase, from community-associated methicillin-resistant Staphylococcus aureus strain USA300, in hydrolyzing triglycerides into growth inhibitory free fatty acids. Journal of bacteriology PMID: 25225262