R E S E A R C H Plasma exposure alters the proteome of S. pyogenes
P R O F I L E S
jected to at the moment, or if they are expressed in different forms on the bacterial surface, this finding has Known virulence factors of Group A the potential to partially explain why Streptococci (GAS), which have been some GAS strains are so difficult to dubbed the “flesh-eating bacteria”, are eradicate during an infection,” explains under tight transcriptional control and Johansson. influenced by environmental factors The collection of up-regulated prosuch as temperature, pH, and ion conteins in human-plasma-exposed bactecentration. Relatively unstudied, howria included more than virulence factors. ever, is the effect of human plasma on Protein metabolism and biosynthesis GAS gene expression. It’s a pertinent proteins were also among the highly exissue; plasma contains a host of defense pressed proteins. Notable among these, mechanisms. “Most streptococcal prothe authors report, are two ribosomal teins that contribute to GAS pathoproteins that catalyze mRNA-directed genesis interact with human plasma protein synthesis and proteins,” says Björn elongation factor G. In Johansson. “Therefore, addition, glycolytic enhuman plasma and its zymes, including glyccomponents are of eraldehyde 3-phosinterest for most perphate dehydrogenase sons trying to under(GADPH), were up-regstand the molecular ulated. GADPH is ininterplay during an volved in glycolysis and infection.” gluconeogenesis and is Johansson, Lars also known to bind Björck, and colleagues plasminogen at the bacat Lund University and terial surface, where it Umeå University (both may play a role as a virin Sweden) set out to ulence factor. probe the bacterium– Interestingly, the plasma relationship by authors report that onusing the GAS bacly two proteins were terium Streptococcus down-regulated in the pyogenes. In this issue plasma-exposed bacteof JPR (pp 2302–2311), ria. One was a 26-kDa they report that expoThe bug. Electron micrograph of GAS strain AP1 colonizing human epithelial cells. hypothetical protein sure to human plasma with no known funchas a profound inflution, and the other was a septum placetwo major GAS virulence factors, are ence on S. pyogenes protein expression, ment protein involved in cell division. not only up-regulated in a plasma envicausing rapid remodeling of its cellular Inactivation of a homologous protein in ronment but also seem to be expressed metabolism and virulence pathways. Bacillus subtilis results in the formation in multiple forms,” says Johansson. The Exotic “flesh-eating” properties of small, mutant anucleate minicells, M1 protein, for instance, was found in 8 aside, S. pyogenes is one of the most but this septum placement protein’s spots, 7 of which were absent from baccommon bacterial pathogens, causing a effect in S. pyogenes is unclear. teria grown in culture medium alone. range of infections in humans, from relThe authors say that their results Similarly, the serine protease C5a peptiatively mild impetigo and pharyngitis to show a profound influence of plasma dase was found in 6 distinct spots. Fursevere septicemia and streptococcal on protein expression, and they suggest ther analysis showed that some of the toxic shock. Post-infectious rheumatic that this response represents an imporM1 protein present in plasma-exposed fever and post-streptococcal glomerutant adaptive mechanism with implicabacteria lacked a portion of the N-terlonephritis can also be serious aftereftions for S. pyogenes pathogenicity. minus. This form of M1 is a previously fects. During the course of an infection, Johansson and colleagues are currently uncharacterized variant. The authors the bacteria can come into contact with characterizing putative proteins identisuggest that the truncated protein had plasma either through vascular leakage fied in this study. Future studies, Jobeen proteolytically processed and that at the infection site as a consequence of hansson says, are planned to look at S. pyogenes, when exposed to human the local inflammatory response or protein expression in other environplasma, may subject virulent proteins when the bacteria penetrate into the ments important for invasive GAS to posttranslational modifications. bloodstream. strains, such as epithelial membranes “Even though we do not know Johansson and colleagues grew the and intracellular compartments. exactly what kind of modifications the AP1 strain of S. pyogenes in the presence —Amy Hodson Thompson M1 protein and C5a peptidase are suband absence of human plasma, harMATTHIAS MÖRGELIN, LUND UNIVERSITY
vested the bacteria at mid-exponential growth phase, and then studied the intracellular proteins by 2DE and MALDITOFMS. They found 8 protein spots that were up-regulated by a factor of ≥2.5 in plasma-exposed bacteria compared with non-exposed and 31 spots that were present only in the plasma-exposed bacteria. These 39 spots represented 24 unique streptococcal proteins that were up-regulated or present only in the plasmaexposed bacteria. “The biggest surprise and the most interesting finding, in my opinion, is that the M1 protein and C5a peptidase,
Journal of Proteome Research • Vol. 4, No. 6, 2005
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