Experimental staphylococcal infections in newborn mice: inhibition of weight gain as an index of virulence

Abstract

MANY ATTEMPTS have been made to set up experimental models to study staphylococcal infections. Often the route of challenge determines the disease produced. Mastitis results from inoculation into the mammary glands of mice and rabbits (Chandler, 1970;Adlam et al., 1976), osteomyelitis from injection into the bone marrow of rabbits (Norden, 1970), and endocarditis from intravenous injection in rabbits and rats (Nickerson et al,. 1969;Santoro and Levison, 1978). In respect of subcutaneous infection, except for a few important studies of experimental infection in man (Elek and Conen, 1957;Maibach, 1965; Marples and Kligman, 1976), most work has been performed on mice. As in most other experimental models of staphylococcal infection, large challenge doses are needed to produce subcutaneous lesions in adult mice, though these can be avoided if the organisms are injected with plugs of cotton dust (Noble, 1965). To assess the virulence of strains of staphylococci in terms of mortality, LD50 measurements have been made after intraperitoneal injections in mice (Chesbro, Wamola and Bartley, 1969), intracerebral injections in newborn mice (Namavar et al., 1976 and and intra-allantoic injections in chick embryos (McCabe, 1964).Recently, McKay and Arbuthnott (1979) showed that newborn mice are more susceptible than adult mice to subcutaneous challenge with staphylococci and compared the virulence of strains by assessing mortality and lesion formation. We have now made a more detailed investigation of this mouse model in an attempt to devise criteria other than mortality for assessing the virulence of staphylococci. MATERIALS AND METHODSBacterial strains. We studied 13 isolates of staphylococci (table I). These included six clinical isolates of Staphylococcus aureus from various infections, four multiple-antibiotic-resistant isolates of S. aureus from a study of hospital cross infection, two isolates of S. epidermidis and the reference "mouse-virulent" strain of S. aureus no. PS80 (NCTC9789).Mouse strain. The Sha Sha strain of mouse was used; this is homozygous from the gene "shaven". The mice never grow a first coat of hair and the adults have only a few short hairs. This "hairless" strain was chosen to study subcutaneous infection because it eliminated the necessity

A Neonatal Model of Intravenous Staphylococcus epidermidis Infection in Mice <24 h Old Enables Characterization of Early Innate Immune Responses

“…Dose range was selected based on experiments demonstrating systemic cytokine responses (e.g., IL-6) at those doses. This range was also consistent with bacterial inocula reported in other murine models [30], [44]. Injections utilized a two-person technique adapted from Kienstra et al (Table 1, Video S1) [45].…”

“…Several newborn mouse models of staphylococcal infection have been described. However, these have largely focused on mice 2 to 7 days of age and employed either intra-peritoneal or subcutaneous routes of infection [29], [30], [31], [32], [33], [34], [35]. Additionally, while lymphoid organ development and immunity in mice at 7 days is comparable to term human neonates, there is little information regarding the ontogeny of the mouse immune system early enough to compare to human preterms [3], [36].…”

“…Using this novel model, we demonstrate that in response to SE bacteremia, newborn mice rapidly and selectively up-regulate transcription of TLR2 and MyD88, and mount a systemic cytokine response. Although these early innate immune responses are associated with clearance of SE infection, this host-pathogen interaction results in impairment of weight gain, an important marker of neonatal well-being [30], [39], [40].…”

Acute haematogenous osteomyelitis: An experimental model

“…Although animal weights were monitored by Norden, detailed analysis of his results in order to predict the presence of osteomyelitic foci in individual experimental animals was not undertaken. Inhibition of normal weight gain has been used to compare the virulence of different strains of staphylococci in newborn mice (Kinsman and Arbuthnott, 1980). In a similar manner, the correlation between chicken growth rate and the presence of osteomyelitis can be applied to evaluate the effectiveness of antibiotics used as therapeutic agents.…”

Sequential release of antigens from chloroform‐treated Staphylococcus epidermidis: application towards a possible vaccine

“…Protection studies were not satisfactory and indeed there is evidence of difficulties even with Staph. aureus using mortality as a reproducible index of infection in adult mice (McKay & Arbuthnott 1979;Kinsman & Arbuthnott 1980). Our findings have been similar with Staph.…”