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Cancers Feb 2023Bacterial cancer therapy is a promising next-generation modality to treat cancer that often uses tumor-colonizing bacteria to deliver cytotoxic anticancer proteins....
Bacterial cancer therapy is a promising next-generation modality to treat cancer that often uses tumor-colonizing bacteria to deliver cytotoxic anticancer proteins. However, the expression of cytotoxic anticancer proteins in bacteria that accumulate in the nontumoral reticuloendothelial system (RES), mainly the liver and spleen, is considered detrimental. This study examined the fate of the strain MG1655 and an attenuated strain of serovar Gallinarum ( Gallinarum) with defective ppGpp synthesis after intravenous injection into tumor-bearing mice (~10 colony forming units/animal). Approximately 10% of the injected bacteria were detected initially in the RES, whereas approximately 0.01% were in tumor tissues. The bacteria in the tumor tissue proliferated vigorously to up to 10 colony forming units/g tissue, whereas those in the RES died off. RNA analysis revealed that tumor-associated activated rrnB operon genes encoding the rRNA building block of ribosome needed most during the exponential stage of growth, whereas those in the RES expressed substantially decreased levels of this gene and were cleared soon presumably by innate immune systems. Based on this finding, we engineered ΔppGpp Gallinarum to express constitutively a recombinant immunotoxin comprising TGFα and the exotoxin A (PE38) using a constitutive exponential phase promoter, the ribosomal RNA promoter rrnB P1. The construct exerted anticancer effects on mice grafted with mouse colon (CT26) or breast (4T1) tumor cells without any notable adverse effects, suggesting that constitutive expression of cytotoxic anticancer protein from rrnB P1 occurred only in tumor tissue.
PubMed: 36900277
DOI: 10.3390/cancers15051486 -
EFSA Journal. European Food Safety... Mar 2023Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a product consisting of four...
Safety and efficacy of a feed additive consisting of the bacteriophages PCM F/00069, PCM F/00070, PCM F/00071 and PCM F/00097 (Bafasal®) for all avian species (Proteon Pharmaceuticals S.A.).
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a product consisting of four bacteriophages infecting ser. Gallinarum B/00111, intended to be used as a zootechnical additive (functional group: other zootechnical additives) for all avian species. The additive (tradename Bafasal®) is not currently authorised in the European Union. Bafasal® is intended to be used in water for drinking and liquid complementary feed to guarantee a minimum daily dose of 2 × 10 PFU/bird, to reduce the spp. contamination of poultry carcasses and load in the environment, and to improve the zootechnical performance of the treated animals. In a previous opinion, the FEEDAP Panel could not conclude on the additive's potential to be irritant or a dermal sensitiser, or on its efficacy for any avian species due to insufficient data. The applicant provided supplementary information to address these data gaps. The new data showed that Bafasal® is not a skin or eye irritant. No conclusions could be drawn on its skin sensitisation potential. The Panel was not in the position to conclude on the efficacy of Bafasal® to improve the zootechnical performance of the target species based on the available data. The additive showed the potential to decrease the counts of two strains of Enteritidis in boots swabs and caecal digesta of chickens for fattening. No conclusions could be drawn on the capacity of Bafasal® to reduce the contamination of other strains, serovars or other species of . The potential of Bafasal® to reduce the spp. contamination poultry carcasses and/or the environment is limited. The FEEDAP Panel recommended a post-market monitoring plan to address the potential selection and spread of resistant variants of to Bafasal®.
PubMed: 36875861
DOI: 10.2903/j.efsa.2023.7861 -
Data in Brief Apr 2023Gallinarum (SG) is a host-restricted enterobacteria and the causative agent of fowl typhoid in poultry. Here, we report the complete genomes of two strains belonging to...
Gallinarum (SG) is a host-restricted enterobacteria and the causative agent of fowl typhoid in poultry. Here, we report the complete genomes of two strains belonging to this serotype. SA68 is a field strain isolated from the livers of dead hen carcasses of a commercial layer farm presenting high mortality located in São Paulo city, Brazil, in 1990. Strain 9R corresponds to a live attenuated SG commercial vaccine. DNA was extracted from pure cultures and subjected to whole genome sequencing (WGS) using the Ion Torrent PGM System. The assemblies reached lengths of 4,657,435 (SA68) and 4,657,471 (9R) base pairs. Complete genomes were deposited in GenBank under the accession numbers CP110192 (SA68) and CP110508 (9R). Both genomes were analyzed and compared in terms of molecular typing, antibiotic resistance genes, virulence genes, Salmonella pathogenic islands (SPIs), insertion sequences and prophages. The data obtained show many similarities in the genetic content, with the exception of the SPI-12 and CS54 pathogenic islands, which are exclusive to the field strain. The information generated will help to understand the virulence differences of field and vaccinal SG strains and can be used to perform evolutionary and epidemiologic studies.
PubMed: 36865996
DOI: 10.1016/j.dib.2023.108959 -
Foods (Basel, Switzerland) Feb 2023() is the most common foodborne pathogen worldwide, leading to massive economic loss and a significant burden on the healthcare system. The primary source of remains...
() is the most common foodborne pathogen worldwide, leading to massive economic loss and a significant burden on the healthcare system. The primary source of remains contaminated or undercooked poultry products. Considering the number of foodborne illnesses with multiple antibiotic resistant , new controlling approaches are necessary. Bacteriophage (phage) therapies have emerged as a promising alternative to controlling bacterial pathogens. However, the limitation on the lysis ability of most phages is their species-specificity to the bacterium. has various serovars, and several major serovars are involved in gastrointestinal diseases in the USA. In this study, bacteriophage-1252 (phage-1252) was isolated and found to have the highest lytic activity against multiple serovars of , including Typhimurium, Enteritidis, Newport, Heidelberg, Kentucky, and Gallinarum. Whole-genome sequencing analysis revealed phage-1252 is a novel phage strain that belongs to the genus Duplodnaviria in the Myoviridae family, and consists of a 244,421 bp dsDNA, with a G + C content of 48.51%. Its plaque diameters are approximately 2.5 mm to 0.5 mm on the agar plate. It inhibited Enteritidis growth after 6 h. The growth curve showed that the latent and rise periods were approximately 40 min and 30 min, respectively. The burst size was estimated to be 56 PFU/cell. It can stabilize and maintain original activity between 4 °C and 55 °C for 1 h. These results indicate that phage-1252 is a promising candidate for controlling multiple serovars in food production.
PubMed: 36832872
DOI: 10.3390/foods12040797 -
Biology Feb 2023Phage therapy is widely being reconsidered as an alternative to antibiotics for the treatment of multidrug-resistant bacterial infections, including salmonellosis caused...
Phage therapy is widely being reconsidered as an alternative to antibiotics for the treatment of multidrug-resistant bacterial infections, including salmonellosis caused by . As facultative intracellular parasites, could spread by vertical transmission and pose a great threat to both human and animal health; however, whether phage treatment might provide an optional strategy for controlling bacterial vertical infection remains unknown. Herein, we explored the effect of phage therapy on controlling the vertical transmission of serovar Gallinarum biovar Pullorum ( Pullorum), a poultry pathogen that causes economic losses worldwide due to high mortality and morbidity. A phage CKT1 with lysis ability against several serovars was isolated and showed that it could inhibit the proliferation of Pullorum in vitro efficiently. We then evaluated the effect of phage CKT1 on controlling the vertical transmission of Pullorum in an adult broiler breeder model. The results demonstrated that phage CKT1 significantly alleviated hepatic injury and decreased bacterial load in the liver, spleen, heart, ovary, and oviduct of hens, implying that phage CKT1 played an active role in the elimination of colonization in adult chickens. Additionally, phage CKT1 enabled a reduction in the -specific IgG level in the serum of infected chickens. More importantly, the decrease in the Pullorum load on eggshells and in liquid whole eggs revealed that phage CKT1 effectively controlled the vertical transmission of Pullorum from hens to laid eggs, indicating the potential ability of phages to control bacterial vertical transmission.
PubMed: 36829587
DOI: 10.3390/biology12020312 -
Veterinary Research Communications Sep 2023Lactic acid bacteria (LAB) are an important option for Salmonella control in animal production, resulting in lower antibiotic use. The objective of this research was to...
Lactic acid bacteria (LAB) are an important option for Salmonella control in animal production, resulting in lower antibiotic use. The objective of this research was to isolate LAB from meat products and from commercial probiotics sold as nutritional supplements for in vitro verification of their bioprotective potential. Eleven bacteria were identified as Pediococcus acidilactici, two as Lacticaseibacillus rhamnosus, one as Lacticaseibacillus paracasei paracasei, one as Limosilactobacillus fermentum, and one as a consortium of Lactobacillus delbrueckii bulgaricus and L. fermentum. All bacteria showed inhibitory activity against Salmonella, with emphasis on the inhibition of P. acidilactici PUCPR 011 against Salmonella Enteritidis 33SUSUP, S. Enteritidis 9SUSP, S. Enteritidis 56301, S. Enteritidis CRIFS 1016, Salmonella Typhimurium ATCC 14,028, and Salmonella Gallinarum AL 1138, with inhibition halos of 7.3 ± 0.5 mm, 7.7 ± 1.0 mm, 9.0 ± 1.8 mm, 7.3 ± 0.5 mm, 7.7 ± 1.0 mm, and 7.3 ± 0.5, respectively. The isolates P. acidilactici PUCPR 011, P. acidilactici PUCPR 012, P. acidilactici PUCPR 014, L. fermentum PUCPR 005, L. paracasei paracasei PUCPR 013, and L. rhamnosus PUCPR 010 showed inhibition greater than 2 mm against at least 3 Salmonella and were used for encapsulation and in vitro digestion. The encapsulation efficiency ranged from 76.89 ± 1.54 to 116.48 ± 2.23%, and the population after 12 months of storage was from 5.31 ± 0.17 to 9.46 ± 0.09 log CFU/g. When simulating swine and chicken digestion, there was a large reduction in bacterial viability, stabilizing at concentrations close to 2.5 log CFU/mL after the analyses. The analyzed bacteria showed strong in vitro bioprotective potential; further analyses are required to determine in vivo effectiveness.
Topics: Animals; Swine; Lactobacillales; Anti-Bacterial Agents; Chickens; Salmonella typhimurium
PubMed: 36823482
DOI: 10.1007/s11259-023-10083-4 -
International Journal of Molecular... Feb 2023Pure cultures of chicken intestinal microbial species may still be crucial and imperative to expound on the function of gut microbiota, and also contribute to the...
Pure cultures of chicken intestinal microbial species may still be crucial and imperative to expound on the function of gut microbiota, and also contribute to the development of potential probiotics and novel bioactive metabolites from gut microbiota. In this study, we isolated and identified 507 chicken intestinal bacterial isolates, including 89 previously uncultured isolates. Among these, a total of 63 strains, belonging to , , , , , and , exhibited antibacterial activity against . Acid tolerance tests showed strain YPG14 ( strain YPG14) has a particularly strong tolerance to acid. We further characterized other probiotic properties of strain YPG14. In simulated intestinal fluid, the growth of strain YPG14 remained stable after incubation for 4 h. The auto-aggregation test showed the auto-aggregation percentage of strain YPG14 was recorded as 15.0 ± 0.38%, 48.3 ± 2.51%, and 75.1 ± 4.44% at 3, 12, and 24 h, respectively. In addition, the mucin binding assay showed strain YPG14 exhibited 12.07 ± 0.02% adhesion to mucin. Antibiotic sensitivity testing showed that strain YPG14 was sensitive to the majority of the tested antibiotics. The anti- Pullorum (. Pullorum) infection effect in vivo revealed that the consumption of strain YPG14 could significantly improve body weight loss and survival rate of chicks infected by . Pullorum; reduce the loads of . Pullorum in the jejunum, liver, spleen, and feces; and alleviate the jejunum villi morphological structure damage, crypt loss, and inflammatory cell infiltration caused by . Pullorum. Overall, this study may help us to understand the diversity of chicken intestinal microflora and provide some insights for potential probiotic development from gut microbiota and may find application in the poultry industry.
Topics: Animals; Gastrointestinal Microbiome; Chickens; Intestines; Limosilactobacillus reuteri; Anti-Bacterial Agents; Probiotics; Mucins
PubMed: 36769368
DOI: 10.3390/ijms24033045 -
Journal of Medical Microbiology Feb 2023
Topics: Animals; Serogroup; Salmonella; Salmonella enterica; Salmonella Infections, Animal; Poultry Diseases; Chickens
PubMed: 36753431
DOI: 10.1099/jmm.0.001653 -
Veterinary Microbiology Mar 2023Salmonella enterica serovar Gallinarum biovar Gallinarum is an avian-adapted pathogen causing fowl typhoid and leading to enormous economic loss in the global poultry...
Salmonella enterica serovar Gallinarum biovar Gallinarum is an avian-adapted pathogen causing fowl typhoid and leading to enormous economic loss in the global poultry industry. Two-component systems (TCSs) are crucial for bacteria survival, virulence, sensing and responding to the environment. 23 pairs of TCSs classified into five families were found in S. Gallinarum strain 287/91, of which the CitB family contains three pairs of TCSs, namely CitA/CitB, DcuS/DcuR and DpiB/DpiA, whose functions remained unaddressed. Thus, four mutants of S. Gallinarum strain U20, ΔcitAB (Δcit), ΔdcuSR (Δdcu), ΔdpiBA (Δdpi) and ΔcitABΔdcuSRΔdpiBA (Δ3), were constructed. The results suggested that the CitB family did not affect the growth or the metabolic capacities tested, while different TCSs exerted various effects on biofilm formation and antimicrobial resistance against multiple drug classes. Furthermore, the CitB family negatively impacted the tolerance of environmental stress, contributing to compromised virulence in chicken embryos and in vivo survival of S. Gallinarum. Collectively, this research provided new knowledge of how the CitB family is involved in the pathogenicity of S. Gallinarum.
Topics: Chick Embryo; Animals; Salmonella enterica; Serogroup; Salmonella; Virulence; Salmonella Infections, Animal; Chickens; Poultry Diseases
PubMed: 36645991
DOI: 10.1016/j.vetmic.2023.109659 -
Frontiers in Veterinary Science 2022In order to prevent pullorum disease and fowl typhoid in breeders, the use of oregano essential oil (OEO) was tested for the prevention and treatment of infections of...
In order to prevent pullorum disease and fowl typhoid in breeders, the use of oregano essential oil (OEO) was tested for the prevention and treatment of infections of multidrug-resistant (SP) and (SG) in commercial Yellow-chicken breeders. In the challenge-protection experiment, commercial Hongguang-Black 1-day-old breeder chicks were randomly divided into four groups, including A (challenged, preventive dose), B (challenged, treatment dose), C (challenged, untreated), and D (unchallenged, untreated). Group A was supplemented with 200 μL/L OEO in the drinking water during the whole trial (1-35 days of age) and group B was supplemented with 400 μL/L OEO during 8-12 days of age, while groups C and D were kept as untreated controls. At 7 days of age, birds of groups A, B, and C were divided into two subgroups with equal number of birds (A-A, B-B, and C-C), and then subgroups A, B, and C were challenged with SP, while subgroups A, B, and C were challenged with SG. Clinical symptoms and death were observed and recorded daily. Every week during the experiment, serum antibodies against SP and SG of all the groups were detected by the plate agglutinate test (PAT). At the age of 35 days, all birds were weighed and necropsied, lesions were recorded and the challenging pathogens were isolated. The results showed that the positive rates of SP and SG isolation in groups A, A and B, B were significantly lower ( < 0.05) than those of groups C and C, respectively, while groups A and A were slightly lower ( > 0.05) than those of groups B and B. The average body weight (BW) of groups A and A were significantly higher ( < 0.05) than those of groups B, B and C, C, respectively, but there was no significant difference ( > 0.05) with that of group D. The -value between PAT positive and the recovery rates of was 0.99, which means they are highly positively correlated. The results of this study demonstrated that the prevention dose (200μL/L) and the treatment dose (400 μL/L) of OEO supplemented in the drinking water could all effectively decrease infections of SP and SG and that the effect of the prevention was greater than that of the treatment and finally that the prevention could also significantly reduce the BW decline of birds challenged with SP and SG.
PubMed: 36619954
DOI: 10.3389/fvets.2022.1058844