Meta-Analysis of Transcriptional Responses to Mastitis-Causing <i>Escherichia coli</i>

<div><p>Bovine mastitis is a widespread disease in dairy cows, and is often caused by bacterial mammary gland infection. Mastitis causes reduced milk production and leads to excessive use of antibiotics. We present meta-analysis of transcriptional profiles of bovine mastitis from 10 studies and 307 microarrays, allowing identification of much larger sets of affected genes than any individual study. Combining multiple studies provides insight into the molecular effects of <i>Escherichia coli</i> infection <i>in vivo</i> and uncovers differences between the consequences of <i>E</i>. <i>coli</i> vs. <i>Staphylococcus aureus</i> infection of primary mammary epithelial cells (PMECs). In udders, live <i>E</i>. <i>coli</i> elicits inflammatory and immune defenses through numerous cytokines and chemokines. Importantly, <i>E</i>. <i>coli</i> infection causes downregulation of genes encoding lipid biosynthesis enzymes that are involved in milk production. Additionally, host metabolism is generally suppressed. Finally, defensins and bacteria-recognition genes are upregulated, while the expression of the extracellular matrix protein transcripts is silenced. In PMECs, heat-inactivated <i>E</i>. <i>coli</i> elicits expression of ribosomal, cytoskeletal and angiogenic signaling genes, and causes suppression of the cell cycle and energy production genes. We hypothesize that heat-inactivated <i>E</i>. <i>coli</i> may have prophylactic effects against mastitis. Heat-inactivated <i>S</i>. <i>aureus</i> promotes stronger inflammatory and immune defenses than <i>E</i>. <i>coli</i>. Lipopolysaccharide by itself induces MHC antigen presentation components, an effect not seen in response to <i>E</i>. <i>coli</i> bacteria. These results provide the basis for strategies to prevent and treat mastitis and may lead to the reduction in the use of antibiotics.</p>