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Robert S. Daum - One of the best experts on this subject based on the ideXlab platform.
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staphylococcus aureus Skin Infection recurrences among household members an examination of host behavioral and pathogen level predictors
Clinical Infectious Diseases, 2015Co-Authors: Loren G Miller, Michael Z. David, Samantha J Eells, Nancy Ortiz, Alexis Taylor, Neha Kumar, Denise Cruz, Susan Boylevavra, Robert S. DaumAbstract:Staphylococcus aureus is a common cause of Infections in community-dwelling persons, especially among those who have contact with the healthcare system and hospitalized patients [1, 2]. Recurrent Infections are commonly reported after initial S. aureus Skin Infection [3–5]. In the United States, the predominant community-associated methicillin-resistant S. aureus (MRSA) clone, USA300 MRSA, has been associated with an upswing in community-associated Skin Infections and recurrent Infections [1, 6]. Recurrence rates have exceeded 50% in some populations [3, 7]. Additionally, community-associated MRSA Infections have high attack rates among household contacts of affected persons [8–10]. The reasons for recurrent Infection are poorly understood. Nasal S. aureus colonization has been associated with subsequent Infections in some populations, especially hospitalized patients [2, 11]. However, the relationship in community-dwelling patients is not strong. Many patients with community-associated S. aureus Infection lack antecedent colonization, suggesting that transmission from other persons may predate Infection [6]. Acquisition of S. aureus from household fomites is another plausible mechanism that can explain recurrent Infections, as it is known that S. aureus contamination of fomites can be found in many households [12–14] and that S. aureus can persist on fomites for months under experimental conditions [15]. In outbreak situations, poor hygienic practices such as sharing towels or inadequate bathing have been associated with a higher risk of S. aureus Infection [16, 17]. However, the role of hygiene in recurrent Infections is poorly understood. Finally, there are data suggesting that the arginine catabolic mobile element (ACME), which is usually carried by USA300 MRSA, is important in spread and virulence [18]. Transcription and translation of genes located on this element could facilitate recurrent Infection. Because data on predictors of recurrent S. aureus Infections are limited to certain populations such as those with human immunodeficiency virus (HIV) Infection [5], we examined predictors of recurrent S. aureus Infection among patients with Skin Infections and their household members in 2 large US cities.
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Host factors that contribute to recurrent staphylococcal Skin Infection.
Current opinion in infectious diseases, 2015Co-Authors: Christopher P. Montgomery, Michael Z. David, Robert S. DaumAbstract:Purpose of reviewStaphylococcus aureus is the most common cause of Skin and soft tissue Infections (SSTI) in the United States and elsewhere. Recurrent Infections occur frequently in patients with S. aureus SSTI, underscoring the need to better understand the nature of protective immunity against th
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protective immunity against recurrent staphylococcus aureus Skin Infection requires antibody and interleukin 17a
Infection and Immunity, 2014Co-Authors: Christopher P. Montgomery, Melvin D. Daniels, Fan Zhao, Anita S. Chong, Marialuisa Alegre, Robert S. DaumAbstract:Although many microbial Infections elicit an adaptive immune response that can protect against reInfection, it is generally thought that Staphylococcus aureus Infections fail to generate protective immunity despite detectable T and B cell responses. No vaccine is yet proven to prevent S. aureus Infections in humans, and efforts to develop one have been hampered by a lack of animal models in which protective immunity occurs. Our results describe a novel mouse model of protective immunity against recurrent Infection, in which S. aureus Skin and soft tissue Infection (SSTI) strongly protected against secondary SSTI in BALB/c mice but much less so in C57BL/6 mice. This protection was dependent on antibody, because adoptive transfer of immune BALB/c serum or purified antibody into either BALB/c or C57BL/6 mice resulted in smaller Skin lesions. We also identified an antibody-independent mechanism, because B cell-deficient mice were partially protected against secondary S. aureus SSTI and adoptive transfer of T cells from immune BALB/c mice resulted in smaller lesions upon primary Infection. Furthermore, neutralization of interleukin-17A (IL-17A) abolished T cell-mediated protection in BALB/c mice, whereas neutralization of gamma interferon (IFN-γ) enhanced protection in C57BL/6 mice. Therefore, protective immunity against recurrent S. aureus SSTI was advanced by antibody and the Th17/IL-17A pathway and prevented by the Th1/IFN-γ pathway, suggesting that targeting both cell-mediated and humoral immunity might optimally protect against secondary S. aureus SSTI. These findings also highlight the importance of the mouse genetic background in the development of protective immunity against S. aureus SSTI.
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Local Inflammation Exacerbates the Severity of Staphylococcus aureus Skin Infection
PloS one, 2013Co-Authors: Christopher P. Montgomery, Melvin D. Daniels, Fan Zhao, Brad Spellberg, Anita S. Chong, Robert S. DaumAbstract:Staphylococcus aureus is the leading cause of Skin Infections. In a mouse model of S. aureus Skin Infection, we found that lesion size did not correlate with bacterial burden. Athymic nude mice had smaller Skin lesions that contained lower levels of myeloperoxidase, IL-17A, and CXCL1, compared with wild type mice, although there was no difference in bacterial burden. T cell deficiency did not explain the difference in lesion size, because TCR βδ (-/-) mice did not have smaller lesions, and adoptive transfer of congenic T cells into athymic nude mice prior to Infection did not alter lesion size. The differences observed were specific to the Skin, because mortality in a pneumonia model was not different between wild type and athymic nude mice. Thus, the clinical severity of S. aureus Skin Infection is driven by the inflammatory response to the bacteria, rather than bacterial burden, in a T cell independent manner.
Christopher P. Montgomery - One of the best experts on this subject based on the ideXlab platform.
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Host factors that contribute to recurrent staphylococcal Skin Infection.
Current opinion in infectious diseases, 2015Co-Authors: Christopher P. Montgomery, Michael Z. David, Robert S. DaumAbstract:Purpose of reviewStaphylococcus aureus is the most common cause of Skin and soft tissue Infections (SSTI) in the United States and elsewhere. Recurrent Infections occur frequently in patients with S. aureus SSTI, underscoring the need to better understand the nature of protective immunity against th
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protective immunity against recurrent staphylococcus aureus Skin Infection requires antibody and interleukin 17a
Infection and Immunity, 2014Co-Authors: Christopher P. Montgomery, Melvin D. Daniels, Fan Zhao, Anita S. Chong, Marialuisa Alegre, Robert S. DaumAbstract:Although many microbial Infections elicit an adaptive immune response that can protect against reInfection, it is generally thought that Staphylococcus aureus Infections fail to generate protective immunity despite detectable T and B cell responses. No vaccine is yet proven to prevent S. aureus Infections in humans, and efforts to develop one have been hampered by a lack of animal models in which protective immunity occurs. Our results describe a novel mouse model of protective immunity against recurrent Infection, in which S. aureus Skin and soft tissue Infection (SSTI) strongly protected against secondary SSTI in BALB/c mice but much less so in C57BL/6 mice. This protection was dependent on antibody, because adoptive transfer of immune BALB/c serum or purified antibody into either BALB/c or C57BL/6 mice resulted in smaller Skin lesions. We also identified an antibody-independent mechanism, because B cell-deficient mice were partially protected against secondary S. aureus SSTI and adoptive transfer of T cells from immune BALB/c mice resulted in smaller lesions upon primary Infection. Furthermore, neutralization of interleukin-17A (IL-17A) abolished T cell-mediated protection in BALB/c mice, whereas neutralization of gamma interferon (IFN-γ) enhanced protection in C57BL/6 mice. Therefore, protective immunity against recurrent S. aureus SSTI was advanced by antibody and the Th17/IL-17A pathway and prevented by the Th1/IFN-γ pathway, suggesting that targeting both cell-mediated and humoral immunity might optimally protect against secondary S. aureus SSTI. These findings also highlight the importance of the mouse genetic background in the development of protective immunity against S. aureus SSTI.
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Local Inflammation Exacerbates the Severity of Staphylococcus aureus Skin Infection
PloS one, 2013Co-Authors: Christopher P. Montgomery, Melvin D. Daniels, Fan Zhao, Brad Spellberg, Anita S. Chong, Robert S. DaumAbstract:Staphylococcus aureus is the leading cause of Skin Infections. In a mouse model of S. aureus Skin Infection, we found that lesion size did not correlate with bacterial burden. Athymic nude mice had smaller Skin lesions that contained lower levels of myeloperoxidase, IL-17A, and CXCL1, compared with wild type mice, although there was no difference in bacterial burden. T cell deficiency did not explain the difference in lesion size, because TCR βδ (-/-) mice did not have smaller lesions, and adoptive transfer of congenic T cells into athymic nude mice prior to Infection did not alter lesion size. The differences observed were specific to the Skin, because mortality in a pneumonia model was not different between wild type and athymic nude mice. Thus, the clinical severity of S. aureus Skin Infection is driven by the inflammatory response to the bacteria, rather than bacterial burden, in a T cell independent manner.
Mohamed N. Seleem - One of the best experts on this subject based on the ideXlab platform.
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Antibacterial activity and therapeutic efficacy of Fl-P(R)P(R)P(L)-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal Skin Infection.
Drug design development and therapy, 2015Co-Authors: Shankar Thangamani, Manish Nepal, Jean Chmielewski, Mohamed N. SeleemAbstract:The antibacterial activities and therapeutic efficacy of the cationic, unnatural proline-rich peptide Fl-P(R)P(R)P(L)-5 were evaluated against multidrug-resistant Staphylococcus aureus in a mouse model of Skin Infection. Fl-P(R)P(R)P(L)-5 showed potent activity against all clinical isolates of S. aureus tested, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA, respectively). Fl-P(R)P(R)P(L)-5 was also superior in clearing established in vitro biofilms of S. aureus and Staphylococcus epidermidis, compared with the established antimicrobials mupirocin and vancomycin. Additionally, topical treatment of an MRSA-infected wound with Fl-P(R)P(R)P(L)-5 enhanced wound closure and significantly reduced bacterial load. Finally, 0.5% Fl-P(R)P(R)P(L)-5 significantly reduced the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in wounds induced by MRSA Skin Infection. In conclusion, the results of this study suggest the potential application of Fl-P(R)P(R)P(L)-5 in the treatment of staphylococcal Skin Infections.
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Efficacy of short novel antimicrobial and anti-inflammatory peptides in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) Skin Infection
Drug design development and therapy, 2014Co-Authors: Mohamed F. Mohamed, Mohamed N. SeleemAbstract:The therapeutic efficacy of two novel short antimicrobial and anti-inflammatory peptides (RR and RRIKA) was evaluated in a mouse model of staphylococcal Skin Infection. RR (2%) and RRIKA (2%) significantly reduced the bacterial counts and the levels of proinflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, in methicillin-resistant Staphylococcus aureus USA 300-0114 Skin lesions. Furthermore, the combined therapy of RRIKA (1%) and lysostaphin (0.5%) had significantly higher antistaphylococcal and anti-inflammatory activity compared to monotherapy. This study supports the potential use of these peptides for topical treatment of methicillin-resistant Staphylococcus aureus Skin Infections.
Zhiqing Pang - One of the best experts on this subject based on the ideXlab platform.
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nanoparticle based antivirulence vaccine for the management of methicillin resistant staphylococcus aureus Skin Infection
Advanced Functional Materials, 2016Co-Authors: Fei Wang, Ronnie H Fang, Brian T Luk, Soracha Thamphiwatana, Diana Dehaini, Pavimol Angsantikul, Ashley V Kroll, Zhiqing PangAbstract:With the rising threat of antibiotic-resistant bacteria, vaccination is becoming an increasingly important strategy to prevent and manage bacterial Infections. Made from deactivated bacterial toxins, toxoid vaccines are widely used in the clinic as they help to combat the virulence mechanisms employed by different pathogens. Herein, the efficacy of a biomimetic nanoparticle-based anti-virulence vaccine is examined in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) Skin Infection. Vaccination with nanoparticle-detained staphylococcal α-hemolysin (Hla) effectively triggers the formation of germinal centers and induces high anti-Hla titers. Compared to mice vaccinated with control samples, those vaccinated with the nanoparticle toxoid show superior protective immunity against MRSA Skin Infection. The vaccination not only inhibits lesion formation at the site of bacterial challenge, but also reduces the invasiveness of MRSA, preventing dissemination into other organs. Overall, this biomimetic nanoparticle-based toxin detainment strategy is a promising method for the design of potent anti-virulence vaccines for managing bacterial Infections.
Philip R Cohen - One of the best experts on this subject based on the ideXlab platform.
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community acquired methicillin resistant staphylococcus aureus Skin Infection an emerging clinical problem
Journal of The American Academy of Dermatology, 2004Co-Authors: Philip R Cohen, Razelle KurzrockAbstract:Community-acquired methicillin-resistant Staphylococcus aureus Skin Infections at an outpatient university health center were evaluated. In all, 41 cultures were performed in 36 of 853 patients. Of the 19 patients with S aureus Infection, methicillin resistance occurred in 10 (53%) and generally manifested as abscesses or cellulitis. Therefore, methicillin resistance should be considered, even in the community setting, and appropriate cultures performed.
