Combatting antimicrobial resistance in bovine mastitis through alternative non-antibiotic strategies
Lead Research Organisation:
Queen's University Belfast
Department Name: Sch of Biological Sciences
Abstract
Milk is increasingly in global demand because it is a nutritious natural food that can be processed into many different products accessible to a wide population, It accounted for 16.4% of total agricultural output in the UK in 2020 and was worth £4.4bn in market prices making the UK the thirteenth-largest milk producer in the world. However, this supply of this important safe food source is under threat due to antimicrobial resistant bacteria that infect the udder of dairy cows, causing mastitis.
Mastitis is an inflammation of the udder caused by microbial infections that compromise milk production, quality and safety. It is the foremost endemic infectious disease which remains a major challenge to the UK, Canada and global dairy industries. Mastitis has a high prevalence and incidence (~35 (UK) and 19 (Canada) cases /per 100/year). Furthermore, clinical management of mastitis is challenging because not just one but the multiple microorganisms are involved in the infection, making it difficult to diagnose. This is further compounded by the fact that many of these microorganisms that cause mastitis no longer respond to current available antibiotic treatments as they have become resistant to these antibiotics.
Antimicrobial resistance (AMR) is closely linked to antimicrobial use and is a major global threat to human health, with projections that it could lead to 5 million human deaths per year. From a public health perspective, AMR in dairy cattle can jeopardize human health, due to the potential spread of mastitic AMR pathogens to humans via consumption of infected dairy products, indirectly when dairy products are disposed of in the environment, or through direct contact with the animals.
AMR bacteria in mastitis infections not only poses a challenge for clinical management of mastitis but poses a threat to UK, Canada and global food security. Antimicrobial residues in milk after treatment also contribute to losses from milk discarded during treatment and from withdrawal period post-treatment. Therefore, alternate, new antibiotic-free treatments are urgently needed to fight AMR in dairy cattle. Consequently, it is paramount that we intensify research to enhance our knowledge about the prevalence of AMR determinants involved in the survival and persistence of mastitis isolates. This is vital for clinical management of the disease and for the development of alternative antibiotic-free treatments.
Over the past 8 years, we have developed and characterised many novel and efficacious antimicrobial peptides (AMPs). Consequently, in this project, we will evaluate the activity of these new, non-toxic AMPs, which have proven antimicrobial and antibiofilm activity against species of multi-drug resistant (MDR) mastitis bacteria.
Additionally, we will assess how treatment of clinical mastitis with these AMP formulations influence the presence and spread of AMR bacteria in dairy cattle. We will also investigate what the microbial and AMR composition of 'normal'/healthy milk versus mastitis milk and evaluate how this changes post treatment with AMPs.
This project is timely as mastitis has been highlighted as a key focus by UK Government. The economic, environmental, and social needs to reduce mastitis in dairy herds require effective, targeted treatments for improved management, and the output from this proposed project will facilitate UK Government goal to combat the AMR challenge.
Mastitis is an inflammation of the udder caused by microbial infections that compromise milk production, quality and safety. It is the foremost endemic infectious disease which remains a major challenge to the UK, Canada and global dairy industries. Mastitis has a high prevalence and incidence (~35 (UK) and 19 (Canada) cases /per 100/year). Furthermore, clinical management of mastitis is challenging because not just one but the multiple microorganisms are involved in the infection, making it difficult to diagnose. This is further compounded by the fact that many of these microorganisms that cause mastitis no longer respond to current available antibiotic treatments as they have become resistant to these antibiotics.
Antimicrobial resistance (AMR) is closely linked to antimicrobial use and is a major global threat to human health, with projections that it could lead to 5 million human deaths per year. From a public health perspective, AMR in dairy cattle can jeopardize human health, due to the potential spread of mastitic AMR pathogens to humans via consumption of infected dairy products, indirectly when dairy products are disposed of in the environment, or through direct contact with the animals.
AMR bacteria in mastitis infections not only poses a challenge for clinical management of mastitis but poses a threat to UK, Canada and global food security. Antimicrobial residues in milk after treatment also contribute to losses from milk discarded during treatment and from withdrawal period post-treatment. Therefore, alternate, new antibiotic-free treatments are urgently needed to fight AMR in dairy cattle. Consequently, it is paramount that we intensify research to enhance our knowledge about the prevalence of AMR determinants involved in the survival and persistence of mastitis isolates. This is vital for clinical management of the disease and for the development of alternative antibiotic-free treatments.
Over the past 8 years, we have developed and characterised many novel and efficacious antimicrobial peptides (AMPs). Consequently, in this project, we will evaluate the activity of these new, non-toxic AMPs, which have proven antimicrobial and antibiofilm activity against species of multi-drug resistant (MDR) mastitis bacteria.
Additionally, we will assess how treatment of clinical mastitis with these AMP formulations influence the presence and spread of AMR bacteria in dairy cattle. We will also investigate what the microbial and AMR composition of 'normal'/healthy milk versus mastitis milk and evaluate how this changes post treatment with AMPs.
This project is timely as mastitis has been highlighted as a key focus by UK Government. The economic, environmental, and social needs to reduce mastitis in dairy herds require effective, targeted treatments for improved management, and the output from this proposed project will facilitate UK Government goal to combat the AMR challenge.
Technical Summary
This proposal deals primarily with the challenge of mastitis related antimicrobial resistance (AMR) in dairy cows, a major dairy production concern causing significant loss of farm income and a threat to food security.
Mastitis is the foremost endemic infectious disease which remains a major challenge to the UK, Canada and global dairy industries due to its high prevalence and incidence (~35 (UK) and 19 (Canada) cases /per 100/year), impact on greenhouse gas production per kg milk due to increased waste and difficulties associated with diagnosis and treatment. It is the most economically significant disease in dairy cattle production costing >£100 million/year in UK and a net annual loss of $794 million (CAD) in Canada due to losses from milk discarded during treatment, costs of treatment/veterinary care etc.
Clinical management of mastitis is challenging because of the multiple etiological agents and this is further aggravated by the problem of antimicrobial resistance as current therapies, based on antibiotics, are often inefficient against mastitis pathogens and their biofilms which promote bacterial persistence in hostile host tissues and increase the risk of disease transmission.
Therefore, prevalence of AMR bacteria in intramammary infections not only poses a challenge for clinical management of mastitis, it is a threat to food security as well as a public health concern given the potential of zoonotic transmission of AMR bacteria or genetic determinants from animals to humans via the food chain and other environmental routes.
In this proposal, we aim to address two shortcomings; 1) understanding the healthy vs mastitic microbiomes and their associated resistomes 2) overcome the AMR problem in mastitis treatment by assessing the efficacy of alternate new non-antibiotic antimicrobial peptide (AMP)therapeutics in the treatment of bovine mastitis, while assessing the effect of these AMPs on AMR abundance and dissemination in mastitic cows.
Mastitis is the foremost endemic infectious disease which remains a major challenge to the UK, Canada and global dairy industries due to its high prevalence and incidence (~35 (UK) and 19 (Canada) cases /per 100/year), impact on greenhouse gas production per kg milk due to increased waste and difficulties associated with diagnosis and treatment. It is the most economically significant disease in dairy cattle production costing >£100 million/year in UK and a net annual loss of $794 million (CAD) in Canada due to losses from milk discarded during treatment, costs of treatment/veterinary care etc.
Clinical management of mastitis is challenging because of the multiple etiological agents and this is further aggravated by the problem of antimicrobial resistance as current therapies, based on antibiotics, are often inefficient against mastitis pathogens and their biofilms which promote bacterial persistence in hostile host tissues and increase the risk of disease transmission.
Therefore, prevalence of AMR bacteria in intramammary infections not only poses a challenge for clinical management of mastitis, it is a threat to food security as well as a public health concern given the potential of zoonotic transmission of AMR bacteria or genetic determinants from animals to humans via the food chain and other environmental routes.
In this proposal, we aim to address two shortcomings; 1) understanding the healthy vs mastitic microbiomes and their associated resistomes 2) overcome the AMR problem in mastitis treatment by assessing the efficacy of alternate new non-antibiotic antimicrobial peptide (AMP)therapeutics in the treatment of bovine mastitis, while assessing the effect of these AMPs on AMR abundance and dissemination in mastitic cows.
