Escherichia coli Mastitis in Dairy Cattle: Etiology, Diagnosis, and Treatment Challenges

Abstract

Bovine mastitis is an inflammation of the udder tissue parenchyma that causes pathological changes in the glandular tissue and abnormalities in milk leading to significant economic losses to the dairy industry across the world. Mammary pathogenic Escherichia (E.) coli (MPEC) is one of the main etiologic agents of acute clinical mastitis in dairy cattle. MPEC strains have virulence attributes to resist the host innate defenses and thrive in the mammary gland environment. The association between specific virulence factors of MPEC with the severity of mastitis in cattle is not fully understood. Furthermore, the indiscriminate use of antibiotics to treat mastitis has resulted in antimicrobial resistance to all major antibiotic classes in MPEC. A thorough understanding of MPEC's pathogenesis and antimicrobial susceptibility pattern is required to develop better interventions to reduce mastitis incidence and prevalence in cattle and the environment. This review compiles important information on mastitis caused by MPEC (e.g., types of mastitis, host immune response, diagnosis, treatment, and control of the disease) as well as the current knowledge on MPEC virulence factors, antimicrobial resistance, and the dilemma of MPEC as a new pathotype. The information provided in this review is critical to identifying gaps in knowledge that will guide future studies to better design diagnostic, prevent, and develop therapeutic interventions for this significant dairy disease.

Keywords: antimicrobial resistance; cattle; host-pathogen interaction; immune response; mammary pathogenic Escherichia coli; mastitis pathogenesis; milk; virulence.

FIGURE 1

The onset of mastitis occurs when MPEC penetrates through the teat canal, multiplies in the teat and gland cisterns, and spreads throughout the milk-producing glandular tissue (A). The multiplication and lysis of MPEC release LPS from the bacteria’s outer membrane (B). LPS binds to the LBP, and the LPS-LBP complex binds to the CD-14, which leads the LPS to a TLR-4 on the surface of macrophage (C). When LPS binds to its respective TLR, an intracellular signaling cascade is activated (NF-κβ), which induces macrophages and mammary epithelial cells to synthesize pro-inflammatory cytokines and acute-phase proteins (D). Chemotactic factors, especially IL-8, then recruit neutrophils from the bloodstream that function as phagocytes at the site of infection in the alveoli (E). The exposure of neutrophils to fat globules and casein leads to loss of cytoplasmic granules (reduced bactericidal activities) and altered morphology (rounding), eliminating pseudopods needed for phagocytosis (F). During phagocytosis, neutrophils release chemicals that eliminate MPEC but also injure mammary epithelial cells, resulting in a permanent decrease in milk production (F). To minimize mammary tissue damage, neutrophils undergo programmed cell death (apoptosis) and release chemokines that attract macrophages to the site of infection (Paape et al., 2003) (G). In the last step of the inflammatory reaction, macrophages quickly phagocytose apoptotic neutrophils (efferocytosis), minimizing the release of granular contents that damage the tissue (H). Interestingly, whereas in the mammary alveolar, dendritic cells are generally non-responsive to MPEC infection.