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Introduction to Pathogens
Staphylococcus aureus
Staphylococcus aureus, belonging to the genus Staphylococcus, is a classic example of a Gram-positive coccus. The bacterial cells typically appear in grape-like clusters, though they can also be found singly, in pairs, or in short chains. They lack flagella, spores, and a capsule, yet exhibit salt tolerance, thriving in media containing more than 10% sodium chloride. When grown on blood agar, S. aureus produces a distinct zone of clear hemolysis (beta-hemolysis), while on SP agar, it develops a characteristic golden-yellow coloration. As illustrated below:
Staphylococcus aureus is an important zoonotic pathogen. This bacterium commonly colonizes the skin, nasal passages, throat, gastrointestinal tract, boils, and suppurating wounds of both humans and animals, and it can also be found everywhere—in the air, wastewater, and other environmental settings.
Staphylococcus aureus can produce a variety of toxins and enzymes, and the bacterium's pathogenicity and virulence are closely linked to these factors. Staphylococcus aureus infections constitute a group of common bacterial diseases, including skin and soft-tissue infections, sepsis, endocarditis, pneumonia, enteritis, meningitis, osteomyelitis, and toxic shock syndrome, among others. Moreover, S. aureus infections can lead to suppurative orchitis in male mice and endometritis in female mice, and they can even be vertically transmitted through the placenta to offspring, severely impacting rodent breeding programs and the progress of animal experiments.
Clinical symptoms and lesions
Healthy, immunocompetent animals typically show no symptoms when infected with Staphylococcus aureus in their skin, intestines, or nasopharynx. Most of the cases identified fall into this category. In healthy animals, S. aureus can be isolated from abscesses or lesion sites. However, the strains isolated from these animals often represent secondary infections at wounds rather than being the primary cause of disease.
The cause of skin infections caused by Staphylococcus aureus is closely tied to rearing conditions, primarily depending on the overall hygiene environment—rather than the presence of S. aureus strains that are typically non-pathogenic. For instance, gerbils kept in suboptimal conditions are highly susceptible to acute, widespread, and purulent dermatitis when infected with S. aureus. Young gerbils (gerbils) are particularly vulnerable, often developing eczematous dermatitis on their faces, noses, feet, legs, and chest/abdominal areas. In contrast, Mongolian gerbils may exhibit mixed infections involving S. aureus alongside other bacterial species within abscesses. Meanwhile, in rabbits, S. aureus can trigger acute septicemia in young offspring. Additionally, S. aureus can be isolated from infected sites such as abscesses, mastitis, hoof dermatitis, and lesions in the reproductive tract.
Susceptible animals, such as mice or other immunodeficient models, can develop purulent infections in the eyes, skin, and genital tract. A classic example is C57BL/6 background mice infected with Staphylococcus aureus, which can lead to balanitis-associated abscesses. Staphylococcus aureus is a well-known opportunistic pathogen that typically triggers infections through broken skin or entry points. It can also cause infections in exposed wounds or damaged skin areas. However, in most cases, Staphylococcus aureus (from the skin) and other Gram-negative bacteria (from fecal sources) are commonly isolated from infected wounds.
Pathogenicity of Staphylococcus aureus in mice
Clinical symptoms
In the early stages, most sick rats exhibit lethargy, reduced appetite, and decreased water intake; their fur stands on end, with fecal matter visibly stuck around the anal area, and some rats curl up in a corner. As the condition worsens, affected rats begin to show labored breathing, develop a bluish discoloration on their facial features, and the subcutaneous injection sites on their abdomens turn bluish-purple. In later stages, the rats become severely debilitated, with their eyes completely sealed by caseous material, and the entire head and face swell dramatically, turning a deep bluish-purple hue. Meanwhile, the subcutaneous injection sites on the abdomen start to form purulent lesions, sometimes even leading to epidermal shedding. Eventually, the rats huddle closely together, showing little to no interest in movement, while the area around their anus becomes red and swollen. Male rats may also develop hard, pus-filled nodules at the base of their penises. In severe cases, the affected rats succumb to exhaustion and ultimately die.
Visible lesions
Widespread lesions were observed in various tissues and organs of the diseased rats. The lungs showed congestion and edema; the liver exhibited congestion and enlargement, with small abscess nodules of varying sizes on its surface. Occasional hemorrhages were noted in the thymus, while the spleen was markedly enlarged and necrotic, revealing multiple necrotic foci of different sizes both on its surface and cut surfaces. The kidneys were swollen and pale in color, and the gastric mucosa was edematous and thickened, with purulent ulcerative lesions appearing either beneath or on the surface. Meanwhile, the mesenteric and serosal small blood vessels were dilated and congested, and the intestinal mucosa displayed small areas of bleeding or pinpoint hemorrhages. The brain and cerebellum were characterized by congestion and edema, while multiple abscess nodules were found in the testes and ovaries. The uterus, meanwhile, showed signs of congestion and edema.
Pathological histological changes
● Lungs: Stasis of blood, perivascular edema and hemorrhage in the pulmonary interstitium, along with plasma cell and lymphocyte infiltration;
● Liver: Stasis of blood, scattered necrosis of the liver parenchyma, and granular degeneration of hepatocytes;
● The spleen: Congestion, reduction and atrophy of splenic corpuscles, along with smooth muscle degeneration and necrosis in the splenic trabeculae;
● Kidneys: Proximal tubule epithelial cells show edema, interstitial blood vessels are dilated, and there is infiltration of plasma cells and lymphocytes.
● Brain: Small blood vessels in the brain tissue dilate, while nerve cells and microglial cells undergo degeneration.
● Testicles: Congestion, edema, and infiltration of macrophages and lymphocytes in the ductal mucosa and interstitial tissue of the seminal vesicles;
● Ovaries: Stasis of blood, edema, red blood cell degeneration, abundant connective tissue, and follicular necrosis;
● Uterus: Congestion, edema, mucosal shedding, abundant glands in the lamina propria, glandular epithelial degeneration, and infiltration of macrophages and lymphocytes.
Golden Staphylococcus Antibiotic Resistance
Drug-resistant Staphylococcus aureus typically refers to methicillin-resistant Staphylococcus aureus (MRSA), a strain of Staphylococcus aureus that is resistant to most beta-lactam antibiotics, antistaphylococcal penicillins (such as methicillin and oxacillin), and cephalosporins. Methicillin resistance is defined as an oxacillin minimum inhibitory concentration equal to or greater than 4 mg/mL.
Detection rates of SA and MRSA in hospitals:
The data comes from the 2020 October to 2021 September monitoring results of the National Bacterial Resistance Surveillance Network in 2021, with a total of 1,434 hospitals reporting the data.
The report revealed that the bacterium with the highest isolation rate among Gram-positive pathogens was Staphylococcus aureus, accounting for 344,515 strains (31.8% of all Gram-positive bacteria). Among these, the national average detection rate of methicillin-resistant Staphylococcus aureus (MRSA) remained steady at 29.4%, unchanged from the previous year.
VRL's detection rates of SA and MRSA over the past 5 years:
In 2018, 3,731 samples were tested, with 58 positive cases; in 2019, 5,284 samples were tested, yielding 70 positive results; in 2020, 6,392 samples were examined, revealing 22 positive cases; in 2021, 7,748 samples were tested, resulting in 21 positive findings; and in 2022, 8,228 samples were analyzed, with 23 positive cases. Over the past five years, infections caused by Staphylococcus aureus in laboratory animals have shown a declining trend.
Some customers requested additional antimicrobial susceptibility testing for animals infected with Staphylococcus aureus. Among the seven S. aureus isolates tested, two were methicillin-resistant S. aureus, with susceptibility results showing that the minimum inhibitory concentration of oxacillin was ≥4 mg/mL. The resistance rate was 28.6%.
Prevention and Control Measures
To prevent the spread of Staphylococcus aureus, animals must be raised in a strictly controlled, exclusion environment—especially immunocompromised mice. This is also one of the main reasons why many immunodeficient mice need to be housed in isolators or micro-isolation units.
Staphylococcus aureus in rodents typically originates from humans, so handlers must carefully cover their skin and wear high-efficiency particulate air (HEPA) masks or N95 respirators. Bacteriophage typing studies have shown that movement of handlers between different facilities is the primary cause of infection among laboratory animals. Routine preventive measures can effectively prevent cross-contamination of Staphylococcus aureus between animals and their caretakers.
Staphylococcus aureus is sensitive to most disinfectants, making any chemical or physical disinfection method highly effective. However, it exhibits remarkable resistance in dry environments, able to survive for weeks on dried skin or skin secretions. While antibiotic treatment can eliminate bacteria in environments like bedding and cages, it fails to eradicate the bacteria harbored within carrier animals. Therefore, antibiotic therapy is not recommended for this purpose.
Animals infected with Staphylococcus aureus should be controlled through embryo transplantation or hysterectomy.
When administering antibiotic treatment for Staphylococcus aureus to large animals such as experimental monkeys, pigs, and dogs, it is essential to prioritize performing susceptibility testing first, to determine the bacteria's resistance profile. This allows veterinarians to select the most appropriate antibiotic for treatment, thereby minimizing the emergence of resistant strains and helping to curb their spread. In clinical veterinary practice, rational use of antimicrobial agents must be carefully considered, as reducing antimicrobial resistance is directly linked to our own health and well-being.
References
Zhang K Y, Tambalo D, Yuan K. *Caenorhabditis elegans* as a Host Model for Studying the Pathogenicity and Virulence of *Staphylococcus aureus* [M]. 2012.
Wullenweber M, Lenz W & Werhan K (1990) Staphylococcus aureus phage types in barrier-maintained colonies of SPF mice and rats. Z Versuchstierkd, 33, 57-61.
Choi CS, Yin CS, Bakar A, et al. (2006) Nasal carriage of Staphylococcus aureus among healthy adults. J Microbiol Immunol Infect, 39, 458-64.
Fox JG, Anderson LC, Lowe FM, and Quimby FW, editors. Laboratory Animal Medicine. 2nd ed. San Diego: Academic Press; 2002. 1325 pp.
Yang Yuqin, Ding Yiyuan, Peng XiuHua, et al. Advances in Research on Animal Models of Staphylococcus aureus Infection [J]. Laboratory Animals and Comparative Medicine, 2011, 31(6):5. DOI: 10.3969/j.issn.1674-5817.2011.06.018.
Gao Zhengqin, Xing Hua, Sun Huai-chang, et al. Experimental Study on the Pathogenicity of Staphylococcus aureus in Mice [J]. Chinese Journal of Comparative Medicine, 2003, 13(2):3. DOI: 10.3969/j.issn.1671-7856.2003.02.007.
National Antimicrobial Resistance Surveillance Network's "2021 National Report on Antimicrobial Resistance"
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