Repeat Staph Infections: Public Health Threat, Immunologic Puzzle

CDC/S. aureus/Public Domain
Staphylococcus aureus is a species of bacteria that is the number one cause of skin and soft tissue infections globally.[1]  Estimates show that about $25 billion[2] is spent yearly on treatment of chronic wounds, including recurrent skin and soft tissue infections. The financial and public health costs of infection with this persistent pathogen are a growing problem, especially in the context of increasing antibiotic resistance to normal courses of treatment. The importance of gaining a deeper understanding of the body’s immune response against these infections is underscored in its recurrent nature: repeat infections occur in more than 50% of patients initially diagnosed with this pathogen.[3]

A number of environmental and epidemiologic risk factors are associated with recurrent S. aureus infection. Individuals who experience frequent exposure to healthcare settings are likely to present with recurrent infection, as well as individuals with diabetes, kidney failure, or an immunocompromising condition such as HIV infection. However, the vast majority of recurrent infections develop in individuals who do not have these risk factors, making S. aureus an intriguing pathogen of public health significance.[4] The host-pathogen (or human-bacterium) interactions offer a window into how and why S. aureus is a serious threat to public health across populations.

The skin serves the dual function of both a physical and immunological barrier. Contained in layers of the skin are a variety of immune cells. Dendritic cells in the epidermis and epithelial cells called keratinocytes express Toll-like receptors (TLRs), which recognize pathogen-associated antigens. This recognition pathway stimulates the expression of inflammatory factors such as cytokines and antimicrobial peptides essential to host (in this case, human) immune responses. Despite the multitude of immune cells that exist in the layers of the skin[5], recurrent infection with S. aureus is common, meaning that immunity against this pathogen is often difficult to develop.

S. aureus employs a number of mechanisms to avoid host defenses, promoting infection of skin and soft tissue.[6] For example, research has shown that most of the antibodies produced against S. aureus only weakly stimulate long-term immune responses, leaving the host vulnerable to frequent infection.[7] The immediate immune response to Staph infection reveals significant over-expression of human host genes involved in short-term immune response and under-expression of genes related to long-term immune response.[8] The public health burden of Staph infections is in part the result of interactions between host skin physiology and the opportunistic nature of the pathogen. This interplay between host immune defenses and S. aureus’s programming to avoid these defenses is currently under further research.



1. Sen, C. K., Gordillo, G. M., Roy, S., Kirsner, R., Lambert, L., Hunt, T. K., Gottrup, F., Gurtner, G. C. and Longaker, M. T. (2009), Human skin wounds: A major and snowballing threat to public health and the economy. Wound Repair and Regeneration, 17: 763–771. doi:10.1111/j.1524-475X.2009.00543.x

2.  Ibid.

3. Miller LG, Eells SJ, David MZ, Ortiz N, Taylor AR, Kumar N, Cruz D, Boyle-Vavra S, Daum RS. Staphylococcus aureus Skin Infection Recurrences Among Household Members: An Examination of Host, Behavioral, and Pathogen-Level Predictors. Clin Infect Dis. 2014


5. Nestle FO, Di MP, Qin JZ, Nickoloff BJ. Skin immune sentinels in health and disease. Nat.Rev.Immunol. 2009;9:679–691.

6. Krishna, S., & Miller, L. S. (2012). Host–pathogen interactions between the skin and Staphylococcus aureus. Current opinion in microbiology, 15(1), 28-35.

7. Pauli NT, Kim HK, Falugi F, Huang M, Dulac J, Dunand CH, Zheng NY, Kaur K, Andrews SF, Huang Y, et al. Staphylococcus aureus infection induces protein A-mediated immune evasion in humans. J Exp Med. 2014

8. Ardura, Monica I., et al. “Enhanced monocyte response and decreased central memory T cells in children with invasive Staphylococcus aureus infections.” PloS one 4.5 (2009): e5446.

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