Targeting of Alpha‐Hemolysin by Active or Passive Immunization Decreases Severity of USA300 Skin Infection in a Mouse Model
Open accessAbstract
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are predominantly those affecting skin and soft tissues. Although progress has been made, our knowledge of the molecules that contribute to the pathogenesis of CA-MRSA skin infections is incomplete. We tested the hypothesis that alpha-hemolysin (Hla) contributes to the severity of USA300 skin infections in mice and determined whether vaccination against Hla reduces disease severity. Isogenic hla-negative (Deltahla) strains caused skin lesions in a mouse infection model that were significantly smaller than those caused by wild-type USA300 and Newman strains. Moreover, infection due to wild-type strains produced dermonecrotic skin lesions, whereas there was little or no dermonecrosis in mice infected with Deltahla strains. Passive immunization with Hla-specific antisera or active immunization with a nontoxigenic form of Hla significantly reduced the size of skin lesions caused by USA300 and prevented dermonecrosis. We conclude that Hla is a potential target for therapeutics or vaccines designed to moderate severe S. aureus skin infections.
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Skin lesions can be attributed to Hla activity.
“Consistent with this, we observed in vivo in the murine skin that the perR::Tn strain induced smaller dermonecrotic lesions, and it is known that skin lesions can be attributed to Hla activity (36).”
From The oxidative stress regulator, PerR, is required for staphyloferrin B-mediated iron acquisition in <i>Staphylococcus aureus</i> (2026) · cites this paper as [36]
Passive immunization with anti-Hla antibodies or active immunization with nontoxigenic Hla is protective in animal models of staphylococcal infection.
“Moreover, passive immunization with anti-Hla antibodies or active immunization with nontoxigenic Hla is protective in animal models of staphylococcal infection [108, 115].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [108]
The ability of staphylococci to acquire heme and hemoproteins in vivo is facilitated by lysis of host erythrocytes by pore-forming toxins such as alpha-hemolysin.
“The ability of staphylococci to acquire heme and hemoproteins in vivo is facilitated by lysis of host erythrocytes by pore-forming toxins such as alpha-hemolysin (encoded by hla) (Fig. 1).”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [108]
Inactivation of alpha-hemolysin limits S. aureus virulence.
“Inactivation of alpha-hemolysin limits the virulence of S. aureus [108–114].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [108]
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References 38 · Cited by 335
Research works printed but not linked: 1
- [22]Bunce C Wheeler L Reed G Musser J Barg N Murine model of cutaneous infection with gram-positive cocci Infect Immun 1992 60 2636 40 1612733 PMC257214
- Authors
- Kennedy, A. D., Wardenburg, J. B., Gardner, D. J., Long, D., Whitney, A. R., Braughton, K. R., Schneewind, O., & DeLeo, F. R.
- Affiliations
- National Institutes of Health (US)
- University of Chicago (US)
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10
- Volume
- 202
- Issue
- 7
- Pages
- 1050-1058
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC2945289
- OpenAlex
- W2163107191
- Cited by
- 335
- References
- 38
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 13 · 2023: 14 · 2022: 13 · 2021: 19 · 2020: 17 · 2019: 24 · 2018: 20 · 2017: 12 · 2016: 24 · 2015: 38 · 2014: 23 · 2013: 37 · 2012: 33
- FWCI
- 20.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (U54AI057153, ZIAAI001079)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
- Health Sciences › Medicine › Infectious Diseases › Dermatological diseases and infestations
- Keywords
- alpha-hemolysin, HLA, community-associated methicillin-resistant Staphylococcus aureus, USA300, skin infections, dermonecrosis, passive immunization, active immunization, vaccination, skin lesions
- MeSH terms
- Animals, Bacterial Toxins, Disease Models, Animal, Female, Hemolysin Proteins, Humans, Immunization, Immunization, Passive, Mice, Inbred BALB C, Skin, Staphylococcal Skin Infections, Staphylococcus aureus, Gene Deletion, Mice
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