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Updated: Aug 23, 2026
Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Mouse mastitis model of infection for antimicrobial compound efficacy studies against intracellular and extracellular
Eric Brouillette1, Gilles Grondin, Céline Lefebvre
1Département de biologie, Faculté des sciences, Centre d'Etude et de Valorisation de la Diversité Microbienne, Université de Sherbrooke, 2500 Boul. Université, Canada J1K 2R1.
Abstract:
Despite the general in vitro susceptibility of Staphylococcus aureus isolates that cause infectious bovine mastitis, the pathogen remains difficult to eradicate with the available antibiotics. The capacity to survive intracellularly has been proposed as a factor contributing to the persistence of S. aureus in the bovine mammary gland. The costs associated with the use of cows or goats to assess the in vivo efficacy of new antibacterial compounds constitute a major drawback. Therefore, in the present study, a mouse model of intramammary infection has been characterized for in vivo testing of new experimental drugs. An inoculum of 100 CFU of S. aureus per gland caused an important level of infection with minimal tissue damage as observed at 24 h post-inoculation. By microscopy, polymorphonuclear neutrophil cell infiltration of the infected mammary glands was observed to increase over time. At 12-24 h of infection, the pathogen was primarily found alive and dividing in neutrophils and occasionally within mammary epithelial cells. Intramuscular or intravenous injections of cephapirin at t = 0 and 10 h reduced the number of CFU/g of gland in a dose-dependent manner. In conclusion, the mouse model of infectious mastitis proposed here is suitable for primary evaluation of experimental drugs after parenteral treatment of intramammary infection with a pathogen such as S. aureus that presents both intracellular and extracellular phases of growth.
Insights
A new mouse model for infectious bovine mastitis caused by Staphylococcus aureus (S. aureus) allows for effective in vivo drug testing. This model aids in evaluating new antibiotics against persistent S. aureus infections.
Area of Science:
- Veterinary Medicine
- Microbiology
- Pharmacology
Background:
- Staphylococcus aureus (S. aureus) causes infectious bovine mastitis but is difficult to eradicate despite in vitro susceptibility.
- Intracellular survival of S. aureus is a proposed mechanism for its persistence in the bovine mammary gland.
- In vivo efficacy testing of new antibacterial drugs using cows or goats is costly and impractical.
Purpose of the Study:
- To characterize a mouse model for intramammary infection to facilitate in vivo testing of experimental drugs.
- To evaluate the suitability of the mouse model for assessing parenteral treatments against S. aureus mastitis.
Main Methods:
- A mouse model of intramammary infection was established using 100 CFU of S. aureus per gland.
- Infected mammary glands were analyzed at 24 hours post-inoculation for infection levels and tissue damage.
- Microscopy was used to observe neutrophil infiltration and pathogen location (intracellular/extracellular) within mammary tissues.
- Cephapirin was administered intramuscularly or intravenously at 0 and 10 hours to assess treatment efficacy.
Main Results:
- The mouse model demonstrated significant infection with minimal tissue damage at 24 hours post-inoculation.
- Polymorphonuclear neutrophil infiltration increased over time in infected mammary glands.
- S. aureus was observed alive and dividing within neutrophils and mammary epithelial cells between 12-24 hours.
- Parenteral cephapirin treatment reduced bacterial load in a dose-dependent manner.
Conclusions:
- The developed mouse model is suitable for the primary in vivo evaluation of experimental drugs for infectious mastitis.
- This model is effective for testing treatments against S. aureus, which exhibits both intracellular and extracellular growth phases.
- The mouse model offers a cost-effective alternative to using large animals for drug efficacy studies.
