Experimental Bacterial Mastitis In The Mouse
TL;DR: Experimental mastitis in the mouse provides a useful model for certain fundamental studies and for experiments, such as those of a screening nature, prior to studies on cattle.
Abstract: Summary
A simple technique was developed for the intramammary inoculation of mice. Experimental mastitis was produced in lactating mice with strains of Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium pyogenes, Pseudomonas aeruginosa and Escherichia coli that had originally been isolated from cases of bovine mastitis. There was evidence that the spectrum of pathogenicity of the different bacterial strains in the bovine species was to some extent paralleled by differences in pathogenicity in the mouse. Mastitis could be produced in BSVS mice by the inoculation of comparatively small numbers of staphylococci. The appearance and histology of the affected mammary glands resembled mastitis produced in the bovine species by the bacterial species concerned. The size of the mouse mammary gland was very convenient for histological and other studies requiring examination of the whole gland. Experimental mastitis in the mouse provides a useful model for certain fundamental studies and for experiments, such as those of a screening nature, prior to studies on cattle.
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TL;DR: Critical developments in vaccine evaluation, including study of polysaccharide-protein conjugate vaccines, offer the potential for enhanced prevention in the relatively near future.
Abstract: Since its emergence 25 years ago, group B streptococcus has become recognized as a cause of serious illness in newborns, pregnant women, and adults with chronic medical conditions. Heavy colonization of the genital tract with group B streptococcus also increases the risk that a woman will deliver a preterm low-birthweight infant. Early-onset infections (occurring at
617 citations
TL;DR: It seems likely that protein A is not an important virulence determinant in mastitis of mice, and the reduced virulence of the protein A-negative mutant U320 compared with the wild-type SA113(83A) may be due to pleiotropic loss of some other unknown virulenceeterminants.
Abstract: Mutants of a genetically well-characterized strain of Staphylococcus aureus [SA113(83A)] were isolated after mutagenization. Alpha-hemolysin- (hla), coagulase- (coa), and protein A- (spa) negative mutants were characterized by more than 90 biochemical tests for production of extracellular proteins and biochemical profile to exclude pleiotropy. Protoplast fusion was then used to isolate double-defective (hla and coa) recombinants and recombinants with regained properties, i.e., production of alpha-hemolysin and coagulase. Studies of such mutants and recombinants in the mouse mastitis model showed that one alpha-hemolysin [SA113(83A) hla-5] and one coagulase-negative [SA113(83A) coa-147] mutant were lower in virulence compared with the wild-type strain SA113(83A). The double-negative mutant SA113(83A) hla-5 coa-147 showed a drastic decline in virulence and only induced very mild changes, as determined by microscopic examinations of infected mammary gland tissue. The recombinant with regained properties, however, was as virulent as the wild-type strain. This suggests that alpha-hemolysin and coagulase are virulence determinants of S. aureus. A high-level protein A-producing mutant (U300) showed the same virulence as the parent strain SA113(83A) in this model. One low virulence protein A-negative mutant (U320) did not markedly increase in virulence when a plasmid containing the cloned gene for protein A (pSPA15) was introduced into this mutant. By these and earlier observations, it seems likely that protein A is not an important virulence determinant in mastitis of mice. The reduced virulence of the protein A-negative mutant U320 compared with the wild-type SA113(83A) may be due to pleiotropic loss of some other unknown virulence determinant(s). Our data confirm earlier findings that pleiotropic changes are common in protein A-negative mutants.
158 citations
TL;DR: The generation of transgenic mice that secrete a potent anti-staphylococcal protein into milk is reported, demonstrating the potential of genetic engineering to combat the most prevalent disease of dairy cattle.
Abstract: Lysostaphin expression in mammary glands confers protection against staphylococcal infection in transgenic mice
145 citations
TL;DR: The animal model results demonstrate the potential of fusion peptidoglycan hydrolases as antimicrobials for the treatment of S. aureus-induced mastitis.
Abstract: Staphylococci cause bovine mastitis, with Staphylococcus aureus being responsible for the majority of the mastitis-based losses to the dairy industry (up to $2 billion/annum). Treatment is primarily with antibiotics, which are often ineffective and potentially contribute to resistance development. Bacteriophage endolysins (peptidoglycan hydrolases) present a promising source of alternative antimicrobials. Here we evaluated two fusion proteins consisting of the streptococcal λSA2 endolysin endopeptidase domain fused to staphylococcal cell wall binding domains from either lysostaphin (λSA2-E-Lyso-SH3b) or the staphylococcal phage K endolysin, LysK (λSA2-E-LysK-SH3b). We demonstrate killing of 16 different S. aureus mastitis isolates, including penicillin-resistant strains, by both constructs. At 100 μg/ml in processed cow milk, λSA2-E-Lyso-SH3b and λSA2-E-LysK-SH3b reduced the S. aureus bacterial load by 3 and 1 log units within 3 h, respectively, compared to a buffer control. In contrast to λSA2-E-Lyso-SH3b, however, λSA2-E-LysK-SH3b permitted regrowth of the pathogen after 1 h. In a mouse model of mastitis, infusion of 25 μg of λSA2-E-Lyso-SH3b or λSA2-E-LysK-SH3b into mammary glands reduced S. aureus CFU by 0.63 or 0.81 log units, compared to >2 log for lysostaphin. Both chimeras were synergistic with lysostaphin against S. aureus in plate lysis checkerboard assays. When tested in combination in mice, λSA2-E-LysK-SH3b and lysostaphin (12.5 μg each/gland) caused a 3.36-log decrease in CFU. Furthermore, most protein treatments reduced gland wet weights and intramammary tumor necrosis factor alpha (TNF-α) concentrations, which serve as indicators of inflammation. Overall, our animal model results demonstrate the potential of fusion peptidoglycan hydrolases as antimicrobials for the treatment of S. aureus-induced mastitis.
138 citations
Cites background from "Experimental Bacterial Mastitis In ..."
...The mouse model of bovine mastitis, developed in the early 1970s (11), is a suitable and relatively inexpensive analysis as a prelude to a cow study (reviewed in references 9 and 48)....
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TL;DR: It is demonstrated that S. aureus was able to cause an intracellular infection in the mouse model of mastitis and that the elimination of one adhesion protein delayed, but did not prevent, infection.
124 citations
Cites methods from "Experimental Bacterial Mastitis In ..."
...The infection model is based on the mouse mastitis model described by Chandler [37]....
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Book•
02 Oct 2013
TL;DR: The nervous system, the endocrine glands, the female genital system, and the male genital system are explained.
Abstract: VOLUME 1 Chapter 1 Bones and joints Chapter 2 Muscle and tendon Chapter 3 The nervous system Chapter 4 The eye and ear Chapter 5 The skin and appendages VOLUME 2 Chapter 1 Alimentary and peritoneum Chapter 2 The liver and biliary system Chapter 3 The pancreas Chapter 4 The urinary system Chapter 5 The respiratory system VOLUME 3 Chapter 1 The cardiovascular system Chapter 2 The hematopoietic system Chapter 3 The endocrine glands Chapter 4 The female genital system Chapter 5 The male genital system
2,460 citations