Alternative treatments for bovine and human mastitis

Abstract

Mastitis, an inflammation of the mammary gland normally caused by infection, is a painful condition with welfare implications recorded both in cows and lactating women. The main treatment for mastitis is the administration of antibiotics for both species. However, there is a compelling need for novel alternative therapies, considering the antibiotic resistance crisis and concomitant problems in the treatment of human and animal infections. Bacteriocins, are a heterogeneous group of small, peptide-based bacterium antimicrobials that have either broad or narrow range inhibition spectra and as such are a viable alternative to antibiotics in some cases. This thesis presents the current strategies to treat mastitis in cows and women. Chapter 1 provides an overview of alternative microbial treatments for bovine mastitis, with focus on probiotics, bacteriocins, phages, and phage endolysins. Chapter 2 examines the microbiology and treatment of human mastitis with Staphylococcus aureus, Staphylococcus epidermidis, and Corynebacterium sp. being identified as the major etiological agents in acute, subacute, and granulomatous mastitis, respectively. Moving forward, Chapter 3 sought to identify the major pathogenic species detected in fifty bovine mastitic milk samples by using cultivation and high-throughput sequencing (HTS). A combination of the two approaches illuminated the polymicrobial complexity of the disease and implied potential for multimicrobial origins of the symptoms. Chapter 4 investigated the milk microbiomes in healthy, subclinical and clinical lactating mothers and evaluated the immune status from these three groups with 37.8% of the asymptomatic women being subclinical. In Chapter 5 insights were provided into using alternative treatments, i.e. nisin A and vancomycin, on S. aureus for biofilm inhibition and eradication. None of the applied treatments were able to eradicate preformed biofilms while the combination treatment significantly inhibited biofilm formation compared with single treatments. Finally, in Chapter 6, 80 strains with antimicrobial activity were isolated from 37 asymptomatic human milk samples. Genome sequencing and in silico analysis of those isolates led to identification of sixteen novel bacteriocins representing all known bacteriocin subclasses. This study suggests that the milk microbiome is a rich source of strains with antimicrobial potential. Overall, the results of this work expand the large body of research that exists in the field of mastitis by exploring the microbiota composition in both mastitic cows and humans and by investigating the pathogens involved and relating it to local immune responses. Furthermore, the efficacy of a bacteriocin as a co-therapy against a mastitis pathogen along with the discovery of novel antimicrobial peptides within the human milk microbiome, suggests that bacteriocins could provide novel therapies for disease treatment and their deployment in the medical sector in the future is a likely prospect.