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, and others. 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 coagulase-negative staphylococcus (CoNS) and a Gram-positive bacterium with a thick cell wall made of a peptidoglycan layer. A coagulase-negative staphylococcus is an organism that can often be detected on the surface of human skin as part of its normal microbiome. In animals and humans, a S. simulans infection can cause bacteremia (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. Figure 1 illustrates a skin infection on a patient’s large toe. In rare cases, infections caused by S. simulans in humans can result in urinary tract infection (UTI), corneal infection, pleural empyema, and pneumonia.

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, butchers, and more. 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 of high mortality in humans” because of an increase in antimicrobial resistance. The new virulent strains can no longer be adequately treated with infections resisting the antibiotics generally used for S. simulans. In animals, infection by S. simulans has been shown to cause mortality in birds, mice, goats, and other animals.

Virulence factors

S. simulans can occur in humans that may have had successively 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. In 2017, a study examining an S. simulans infection transmitted to a human by broiler chickens tested four independent isolates of the pathogen to identify virulence factors. All four were positive for protease and slime production. Protease is a degradative component secreted by the pathogen to infect, lyse and damage host cells. 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. Slime production (biofilm), particularly for CoNS pathogens, is extremely important. It is with the slime production that the pathogen can 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, and tissue necrosis cytotoxin Panton-Valentine leukocidin, and the methicillin-resistance gene, mecA. Although mecA does not contribute to the bacterium’s virulence, an increase in pathogenicity has been noticed in human infections of S. simulans and the methicillin-resistance gene may be at fault. Although antibiotic resistance is not a virulence factor, as the pathogen becomes more resistant to antibiotic treatment, the harder it becomes to treat the infection, and the longer S. simulans may remain in the host and cause tissue damage. Figure 2 illustrates biofilm produced by the S. aureus bacteria, a close cousin to S. simulans, and although not the same pathogen, their biofilm production is very similar and works for the same purpose: protecting the microorganism from the immune system.

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 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 the susceptibility of the host to the medication such as allergies and underlying diseases must be taken into consideration.

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