Abstract
BackgroundFor more than 100 years, group A Streptococcus has been identified as a cause of severe and, in many cases, fatal infections of the female urogenital tract. Due to advances in hospital hygiene and the advent of antibiotics, this type of infection has been virtually eradicated. However, within the last three decades there has been an increase in severe intra- and post-partum infections attributed to GAS.MethodologyWe hypothesized that GAS alters its transcriptome to survive in human amniotic fluid (AF) and cause disease. To identify genes that were up or down regulated in response to growth in AF, GAS was grown in human AF or standard laboratory media (THY) and samples for expression microarray analysis were collected during mid-logarithmic, late-logarithmic, and stationary growth phases. Microarray analysis was performed using a custom Affymetrix chip and normalized hybridization values derived from three biological replicates were collected at each growth point. Ratios of AF/THY above a 2-fold change and P-value <0.05 were considered significant.Principal FindingsThe majority of changes in the GAS transcriptome involved down regulation of multiple adhesins and virulence factors and activation of the stress response. We observed significant changes in genes involved in the arginine deiminase pathway and in the nucleotide de novo synthesis pathway.Conclusions/SignificanceOur work provides new insight into how pathogenic bacteria respond to their environment to establish infection and cause disease.
Highlights
Group A Streptococcus (Streptococcus pyogenes, GAS) is an exclusively human, Gram-positive pathogen that causes a broad variety of diseases from mild pharyngitis and skin infections to necrotizing fasciitis, streptococcal toxic shock syndrome, and non-suppurative sequelae such as acute rheumatic fever or glumerulonephritis
Samples were collected from three pooled amniotic fluid (AF) cultures after 3.5, 5, and 9 hours of growth in AF, which corresponds to bacteria in mid log (ML) growth phase, late log (LL, time point corresponding with the transition from log to stationary phase) and stationary (S) phase, respectively
Recent detailed compositional analysis of AF revealed the presence of multiple proteins [21], glucose, fructose, lipids, hormones, and epithelial cells
Summary
Group A Streptococcus (Streptococcus pyogenes, GAS) is an exclusively human, Gram-positive pathogen that causes a broad variety of diseases from mild pharyngitis and skin infections to necrotizing fasciitis, streptococcal toxic shock syndrome, and non-suppurative sequelae such as acute rheumatic fever or glumerulonephritis (for a review see [1]). Since the 1980’s, GAS has re-emerged as an important cause of severe invasive infections and is estimated to cause approximately 500,000 deaths each year globally despite available antibiotic treatment [2]. In the late 1800’s, GAS was identified as a causative factor of puerperal sepsis – a severe invasive infection in post partum women [3]. Due to advances in hospital hygiene, namely physicians washing their hands between deliveries, these types of GAS infections became less frequent. For more than 100 years, group A Streptococcus has been identified as a cause of severe and, in many cases, fatal infections of the female urogenital tract. Due to advances in hospital hygiene and the advent of antibiotics, this type of infection has been virtually eradicated.
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