Staphylococcus simulans

by Marianne Lessard Mastine & Kimberly Zajac

Introduction

Staphylococcus simulans is an opportunistic animal pathogen often associated with domestic and farm animals such as cows, horses, goats, chickens, dogs, hedgehogs, birds, turkeys, etc. S. simulans is very rarely found on human skin but reports of infections with individuals working in close contact with animals, such as veterinarians and butchers, have been recorded.

Disease

As an opportunistic pathogen, S. simulans generally only cause disease when the infected host’s immune system is compromised. Therefore a weakened host already battling another infection could prompt S. simulans to infect and cause damage to the individual. In addition, S. simulans is a coagulase-negative staphylococci (CoNS) and a gram positive bacterium with a thick cell wall made of a peptidoglycan layer. A coagulase-negative staphylococci is an organism that can often be detected on the surface of human skin as part of its normal microbiome. S. simulans produce large quantities of slime, a factor that greatly enhances the bacteria’s ability to infect its host. Moreover, slime production helps S. simulans protect itself from the immune system of the host by creating an envelope of biofilm that surrounds the bacteria and is difficult to degrade by immune cells.. After the bacteria has colonized the host, S. simulans secrete proteases, a destructive substance, that damages host tissues. In animals and humans, an S. simulans infection can cause bacteraemia (i.e. bacterial infection in the bloodstream), endocarditis, post-surgical and vertebral osteomyelitis, and prosthetic joint infection. Specifically in animals, S. simulans can cause lameness in broiler chickens, ear infections in dogs, pyoderma (i.e. bacterial skin infection common in dogs), and is predominantly associated with bovine mastitis. In humans, S. simulans infection is associated with nausea, dysuria and skin and soft tissue infection. In rare cases, infections caused by S. simulans in humans can result in urinary tract infection (UTI), corneal infection, pleural empyema, and pneumonia.

Figure 1. S. simulans skin infection of the big toe (Source: Shields et al., 2016)

Epidemiology

Reports of S. simulans infections in humans are uncommon and generally appear in individuals who are in frequent contact with animals such as farmers, animal facility workers, veterinarians, etc.. In some cases, animals are not the source of infection and the mode of bacterial contamination by S. simulans is unclear. In general, infections are more common in elders and immunosuppressed individuals whose immune system is weakened. Unfortunately, new evidence suggests that S. simulans is “emerging as an important cause of virulent infections with high mortality in humans” because of an increase in antimicrobial resistance. In animals, infection by S. simulans has shown to cause mortality in birds, mice, goats, etc..

Virulence factors

Staphylococcus simulans can occur in humans that may have had successive repeated interactions with an animal that is infected. Because of its rareness, there are not many cases that have been studied explaining the pathogenic pathway and how it may infect the host. A 2017 study examining an S. simulans infection transmitted to a human by broiler chickens tested four independent isolates of the pathogen to identify virulence factors. Of these four, they were all determined to be “positive for protease, and slime production”. Protease is a degradative component secreted by the pathogen to infect, lyse and damage host cells. As mentioned, slime production (biofilm), particularly for CoNS pathogens, is extremely important because it protects the organism from the defense mechanisms enacted by the host. It is with the slime production that the pathogen is able to colonize smooth surfaces, such as prosthetic devices, catheters, and shunts and survive in the host. The slime layer produced by S. simulans has an antiphagocytic effect and mediates protection by preventing immune cells from phagocytosing the pathogen and destroying it with degradative enzymes. Furthermore, S. simulans appear to share virulence factors with Staphylococcus aureus, another CoNS pathogen. For example, both bacteria share the following virulence factors: staphylococcal enterotoxins, tissue necrosis cytotoxin Panton–Valentine leukocidin, and the methicillin-resistance gene, mecA. An increase in pathogenicity has been noticed in human infections of S. simulans and the methicillin-resistance gene virulence factor may be at fault. Indeed, as the pathogen becomes more resistant to antibiotic treatment, the more virulent and potentially harmful it becomes. 

Figure 2. S. simulans bacteria producing biofilm (shown as a clear halo around pathogen) to protect itself from the host’s immune system (Source: Anderson and Wilson, 1981

Treatment

In general, an S. simulans infection can be effectively treated with ceftriaxone, clindamycin, ciprofloxacin, and sulfamethoxazole-trimethoprim, all of which are antibiotics. Diverse treatments have been tested in different studies, showing S. simulans were resistant to some therapies and susceptible to others. For instance, in addition the the aforementioned antibiotics, the pathogen is susceptible to erythromycin, florfenicol, gentamicin, neomycin, penicillin, streptomycin, tetracycline, vancomycin and amikacin; again, all antibiotics. For now, most antibiotic treatments are successful at eliminating infection, but host susceptibility to the medication must be taken into consideration (allergies, underlying disease, etc.). 

References

Anderson, J. C., & Wilson, C. D. (1981). Encapsulated, coagulase-negative strain of Staphylococcus simulans. Infection and Immunity, 33(1), 304–308. PubMed. https://doi.org/10.1128/iai.33.1.304-308.1981

da Silva, E. R., Siqueira, A. P., Martins, J. C. D., Ferreira, W. P. B., & da Silva, N. (2004). Identification and in vitro antimicrobial susceptibility of Staphylococcus species isolated from goat mastitis in the Northeast of Brazil. Small Ruminant Research, 55(1), 45–49. https://doi.org/10.1016/j.smallrumres.2004.01.001

de, M. do C., Bastos, F., Coutinho, B. G., & Coelho, M. L. V. (2010). Lysostaphin: A Staphylococcal Bacteriolysin with Potential Clinical Applications. Pharmaceuticals, 3(4), 1139–1161. Research Library. https://doi.org/10.3390/ph3041139

Drobeniuc, A., Traenkner, J., Rebolledo, P. A., Ghazaryan, V., & Rouphael, N. (2021). Staphylococcus simulans: A rare uropathogen. IDCases, 25, e01202–e01202. PubMed. https://doi.org/10.1016/j.idcr.2021.e01202

Lal, A., Akhtar, J., Ullah, A., & Abraham, G. M. (2018). First Case of Pleural Empyema Caused by Staphylococcus simulans: Review of the Literature. Case Reports in Infectious Diseases, 2018, e7831284. https://doi.org/10.1155/2018/7831284

Males, B. M., Bartholomew, W. R., & Amsterdam, D. (1985). Staphylococcus simulans septicemia in a patient with chronic osteomyelitis and pyarthrosis. Journal of Clinical Microbiology, 21(2), 255–257. PubMed. https://doi.org/10.1128/jcm.21.2.255-257.1985

Penna, B., Varges, R., Medeiros, L., Martins, G. M., Martins, R. R., & Lilenbaum, W. (2009). In vitro antimicrobial susceptibility of staphylococci isolated from canine pyoderma in Rio de Janeiro, Brazil. Brazilian Journal of Microbiology, 40, 490–494. https://doi.org/10.1590/S1517-83822009000300011

Shields, B. E., Tschetter, A. J., & Wanat, K. A. (2016). Staphylococcus simulans: An emerging cutaneous pathogen. JAAD Case Reports, 2(6), 428–429. PubMed. https://doi.org/10.1016/j.jdcr.2016.08.015

Smith, D. A., & Nehring, S. M. (2021). Bacteremia. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK441979/

Stępień-Pyśniak, D., Wilczyński, J., Marek, A., Śmiech, A., Kosikowska, U., & Hauschild, T. (2017). Staphylococcus simulans associated with endocarditis in broiler chickens. Avian Pathology, 46(1), 44–51. https://doi.org/10.1080/03079457.2016.1203392

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