Zoonoses are infectious diseases transmitted directly or indirectly between animals and humans. Several important zoonotic pathogens colonize farm animals asymptomatically, which may lead to ...contamination of the food chain and public health hazards. Moreover, routine sampling of carcasses at retail by government authorities over the past 20 years suggests the prevalence of antibiotic resistance in foodborne pathogens has increased. If this continues, antibiotics may be ineffective against such pathogens in the future and alternative approaches, such as phage therapy, may be necessary. Intensive livestock farming is the only realistic way of meeting the demand for meat from an increasing global population and growth in middle class consumers in developing countries, particularly in Asia. This review elaborates on the use of phages to control zoonotic pathogens in intensively-reared livestock (poultry and pigs).
Antimicrobial resistance (AMR) is a global health and economic crisis. With too few antibiotics in development to meet current and anticipated needs, there is a critical need for new therapies to ...treat Gram-negative infections. One potential approach is the use of living predatory bacteria, such as
(small Gram-negative bacteria that naturally invade and kill Gram-negative pathogens of humans, animals and plants). Moving toward the use of
as a 'living antibiotic' demands the investigation and characterization of these bacterial predators in biologically relevant systems. We review the fundamental science supporting the feasibility of predatory bacteria as alternatives to antibiotics.
Multidrug-resistant
Salmonella Typhimurium U288 is a significant pathogen of pigs, accounting for over half of all outbreaks on UK pig production premises. The potential of this serovar, and other ...salmonellae, to enter the food chain during the slaughtering process requires that efforts be made to reduce the prevalence of these bacteria at both the pre- and post-harvest stages of production. A bacteriophage cocktail (PC1) capable of lysing various
Salmonella enterica serovars was designed using the broad host-range phage Felix 01, and three phages isolated from sewage. PC1 applied to pig skin experimentally-contaminated with U288 achieved significant reductions (P
<
0.05) in
Salmonella counts when stored at 4
°C over 96
h. Reductions of >
1 log
10 unit were observed when the ratio of phage applied was in excess of the bacterial concentration. The treatment was found to be effective at a multiplicity of infection (MOI) of 10 or above, with no significant reductions taking place when the MOI was less than 10. Under these conditions U288 counts of log
10 4.1–4.3 CFU were reduced to undetectable levels following the application of PC1 to pig skin (>
99% reduction). These data suggest phage cocktails could be employed post-slaughter as a means to reduce
Salmonella contamination of pig carcasses.
► We report a bacteriophage cocktail able to lyse several
Salmonella enterica serovars. ► Biosanitization of multi-drug resistant
S. Typhimurium U288 contaminating pig skin. ► Passive phage therapy reductions require a multiplicity of infection
≥
10.
Pseudomonas spp. in Canine Otitis Externa Secker, Bailey; Shaw, Stephen; Atterbury, Robert J.
Microorganisms (Basel),
11/2023, Letnik:
11, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Canine otitis externa (OE) is a commonly diagnosed condition seen in veterinary practice worldwide. In this review, we discuss the mechanisms of the disease, with a particular focus on the biological ...characteristics of Pseudomonas aeruginosa and the impact that antibiotic resistance has on successful recovery from OE. We also consider potential alternatives to antimicrobial chemotherapy for the treatment of recalcitrant infections. P. aeruginosa is not a typical constituent of the canine ear microbiota, but is frequently isolated from cases of chronic OE, and the nature of this pathogen often makes treatment difficult. Biofilm formation is identified in 40–95% of P. aeruginosa from cases of OE and intrinsic and acquired antibiotic resistance, especially resistance to clinically important antibiotics, highlights the need for alternative treatments. The role of other virulence factors in OE remains relatively unexplored and further work is needed. The studies described in this work highlight several potential alternative treatments, including the use of bacteriophages. This review provides a summary of the aetiology of OE with particular reference to the dysbiosis that leads to colonisation by P. aeruginosa and highlights the need for novel treatments for the future management of P. aeruginosa otitis.
Nontyphoidal Salmonella spp. are a leading cause of human food poisoning and can be transmitted to humans via consuming contaminated pork. To reduce Salmonella spread to the human food chain, ...bacteriophage (phage) therapy could be used to reduce bacteria from animals' preslaughter. We aimed to determine if adding a two-phage cocktail to feed reduces Salmonella colonization in piglets. This first required spray drying phages to allow them to be added as a powder to feed, and phages were spray dried in different excipients to establish maximum recovery. Although laboratory phage yields were not maintained during scale up in a commercial spray dryer (titers fell from 3 × 10
to 2.4 × 10
PFU/g respectively), the phage titers were high enough to progress. Spray dried phages survived mixing and pelleting in a commercial feed mill, and sustained no further loss in titer when stored at 4°C or barn conditions over 6 months. Salmonella-challenged piglets that were prophylactically fed the phage-feed diet had significantly reduced Salmonella colonization in different gut compartments (
< 0.01). 16S rRNA gene sequencing of fecal and gut samples showed phages did not negatively impact microbial communities as they were similar between healthy control piglets and those treated with phage. Our study shows delivering dried phages via feed effectively reduces Salmonella colonization in pigs.
Infections caused by Salmonella spp. cause 93.8 million cases of human food poisoning worldwide, each year of which 11.7% are due to consumption of contaminated pork products. An increasing number of swine infections are caused by multidrug-resistant (MDR) Salmonella strains, many of which have entered, and continue to enter the human food chain. Antibiotics are losing their efficacy against these MDR strains, and thus antimicrobial alternatives are needed. Phages could be developed as an alternative approach, but research is required to determine the optimal method to deliver phages to pigs and to determine if phage treatment is effective at reducing Salmonella colonization in pigs. The results presented in this study address these two aspects of phage development and show that phages delivered via feed prophylactically to pigs reduces Salmonella colonization in challenged pigs.
Bacteria are preyed upon by diverse microbial predators, including bacteriophage and predatory bacteria, such as
While bacteriophage are used as antimicrobial therapies in Eastern Europe and are ...being applied for compassionate use in the United States, predatory bacteria are only just beginning to reveal their potential therapeutic uses. However, predation by either predator type can falter due to different adaptations arising in the prey bacteria. When testing poultry farm wastewater for novel
isolates on
prey lawns, individual composite plaques were isolated containing both an RTP (rosette-tailed-phage)-like-phage and a
strain and showing central prey lysis and halos of extra lysis. Combining the purified phage with a lab strain of
HD100 recapitulated haloed plaques and increased killing of the
prey in liquid culture, showing an effective side-by-side action of these predators compared to their actions alone. Using approximate Bayesian computation to select the best fitting from a variety of different mathematical models demonstrated that the experimental data could be explained only by assuming the existence of three prey phenotypes: (i) sensitive to both predators, (ii) genetically resistant to phage only, and (iii) plastic resistant to
only. Although each predator reduces prey availability for the other, high phage numbers did not abolish
predation, so both predators are competent to coexist and are causing different selective pressures on the bacterial surface while, in tandem, controlling prey bacterial numbers efficiently. This suggests that combinatorial predator therapy could overcome problems of phage resistance.
With increasing levels of antibiotic resistance, the development of alternative antibacterial therapies is urgently needed. Two potential alternatives are bacteriophage and predatory bacteria. Bacteriophage therapy has been used, but prey/host specificity and the rapid acquisition of bacterial resistance to bacteriophage are practical considerations. Predatory bacteria are of interest due to their broad Gram-negative bacterial prey range and the lack of simple resistance mechanisms. Here, a bacteriophage and a strain of
, preyed side by side on a population of
, causing a significantly greater decrease in prey numbers than either alone. Such combinatorial predator therapy may have greater potential than individual predators since prey surface changes selected for by each predator do not protect prey against the other predator.
Retail poultry products are widely purported as the major infection vehicle for human campylobacteriosis. Numerous intervention strategies have sought to reduce Campylobacter contamination on broiler ...carcasses in the abattoir. This study reports the efficacy of bacteriophage in reducing the number of recoverable Campylobacter jejuni cells on artificially contaminated chicken skin.
Abstract
Cholera remains a major risk in developing countries, particularly after natural or man-made disasters. Vibrio cholerae El Tor is the most important cause of these outbreaks, and is becoming ...increasingly resistant to antibiotics, so alternative therapies are urgently needed. In this study, a single bacteriophage, Phi_1, was used to control cholera prophylactically and therapeutically in an infant rabbit model. In both cases, phage-treated animals showed no clinical signs of disease, compared with 69% of untreated control animals. Bacterial counts in the intestines of phage-treated animals were reduced by up to 4 log10 colony-forming units/g. There was evidence of phage multiplication only in animals that received a V. cholerae challenge. No phage-resistant bacterial mutants were isolated from the animals, despite extensive searching. This is the first evidence that a single phage could be effective in the treatment of cholera, without detectable levels of resistance. Clinical trials in human patients should be considered.
causes opportunistic infections in dogs. It also has significant zoonotic potential, with the emergence of multidrug resistance leading to difficulty treating both animal and human infections. Manuka ...honey has previously been reported to inhibit many bacterial pathogens, including methicillin-resistant
, and is successfully utilized in both clinical and veterinary practice. Here, we evaluated the ability of manuka honey to inhibit strains of
grown alone and in combination with antibiotics, as well as its capacity to modulate virulence within multiple
isolates. All 18 of the genetically diverse
strains sequenced and tested were inhibited by ≤12% (wt/vol) medical-grade manuka honey, although tolerance to five clinically relevant antibiotics was observed. The susceptibility of the isolates to four of these antibiotics was significantly increased (
≤ 0.05) when combined with sublethal concentrations of honey, although sensitivity to oxacillin was decreased. Virulence factor (DNase, protease, and hemolysin) activity was also significantly reduced (
≤ 0.05) in over half of isolates when cultured with sublethal concentrations of honey (13, 9, and 10 isolates, respectively). These findings highlight the potential for manuka honey to be utilized against
infections.
is an important member of the skin microbial community in animals and can cause opportunistic infections in both pets and their owners. The high incidence of antimicrobial resistance in
highlights that this opportunistic zoonotic pathogen can cause infections which require prolonged and intensive treatment to resolve. Manuka honey has proven efficacy against many bacterial pathogens and is an accepted topical treatment for infections in both veterinary and clinical practice, and so it is a particularly appropriate antimicrobial for use with zoonotic pathogens such as
Here, we demonstrate that not only is manuka honey highly potent against novel multidrug-resistant
isolates, it also acts synergistically with clinically relevant antibiotics. In addition, manuka honey modulates
virulence activity, even at subinhibitory concentrations. In a clinical setting, these attributes may assist in controlling infection, allowing a more rapid resolution and reducing antibiotic use.
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