Meta-Analysis of Transcriptional Responses to Mastitis-Causing Escherichia coli

Abstract

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 Escherichia coli infection in vivo and uncovers differences between the consequences of E. coli vs. Staphylococcus aureus infection of primary mammary epithelial cells (PMECs). In udders, live E. coli elicits inflammatory and immune defenses through numerous cytokines and chemokines. Importantly, E. coli 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 E. coli 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 E. coli may have prophylactic effects against mastitis. Heat-inactivated S. aureus promotes stronger inflammatory and immune defenses than E. coli. Lipopolysaccharide by itself induces MHC antigen presentation components, an effect not seen in response to E. coli bacteria. These results provide the basis for strategies to prevent and treat mastitis and may lead to the reduction in the use of antibiotics.

The genomic architecture of mastitis resistance in dairy sheep

“…A previous study identified genes involved in response to bacterial lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, in a mouse mammary gland model of mastitis [ 28 ]. A similar model of mastitis has also been implemented in dairy cattle [ 29 – 31 ]. We reasoned that genes involved in mastitis susceptibility would likely be constitutively expressed in the mammary gland and immune tissues and/or differentially expressed in sheep bone marrow-derived macrophages (BMDMs) in response to LPS treatment.…”

Integration of machine learning and meta-analysis identifies the transcriptomic bio-signature of mastitis disease in cattle

“…Importantly, based on our results, E . coli infection causes down-regulation of genes encoding lipid biosynthesis enzymes including ALOX15 , FASN , GPAM , TM7SF2 that are involved in milk production [ 37 ]. Generally, in infection, host metabolism is suppressed because the tissue has to divert energy to fight infection.…”

“…coli and Staphylococcus aureus strains infections and also between lipopolysaccharide (LPS), and E . coli -induced mastitis [ 37 ].…”

Vaccination with a live-attenuated small-colony variant improves the humoral and cell-mediated responses against Staphylococcus aureus

“…coli or S . aureus IMIs were lately demonstrated to be very contrasting [38,39], at least partly because of the high inflammatory response to LPS found in Gram negative bacteria [40], whereas S . aureus can modulate and subverts host responses by suppressing pro-inflammatory pathways [41].…”