Identification of In Vivo–Expressed Antigens of<i>Staphylococcus aureus</i>and Their Use in Vaccinations for Protection against Nasal Carriage

Clarke, Simon; K, Brummell; Horsburgh, Malcolm J.; McDowell, Philip W.; Mohamad, Sharifah Aminah Syed; Stapleton, Melanie R.; Arroyo-Acevedo, Jorge Luis; Read, Robert C.; Day, Nicholas P. J.; Peacock, Sharon J.; Mond, James J.; Kokai‐Kun, John F.; Foster, Simon J.

doi:10.1086/501471

Cited by 185 publications

(200 citation statements)

References 44 publications

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“…Adherence is proposed to occur either through nonspecific hydrophobic interactions or via specific interactions between components of host cell membranes and surface proteins of S. aureus (28). S. aureus surface components, such as IsdA, ClfB, and wall teichoic acids, have roles in adherence to nasal epithelial cells and nasal colonization (10,41,57). Interestingly, both AhpC and KatA were required for nasal colonization by S. aureus in a cotton rat model of infection.…”

Section: Discussionmentioning

confidence: 99%

“…The cotton rat (Sigmodon hispidus) has been used to study human respiratory pathogens, due to its susceptibility to human diseases and similarity in disease progression and its epithelial tissue, which is comparable to that of humans (29). Nasal colonization by ahpC and katA mutants and the wild type was tested as described previously (10). The numbers of bacteria recovered from KC041 (ahpC) (P Ͻ 0.001), KS100 (katA) (P Ͻ 0.001), and KC043 (ahpC katA) (P Ͻ 0.001) were significantly reduced compared to the wild type (Fig.…”

Section: Vol 189 2007 Peroxide Stress Resistance Proteins Of S Aurmentioning

confidence: 99%

“…Thus, under high Fe(II) conditions, the increase in catalase reduces the level of H 2 O 2 and prevents the formation of toxic hydroxyl radicals. In many bacteria, including S. aureus, the role of Fur is primarily in iron homeostasis (10,17,58). Fur binds to a consensus sequence, designated the Fur box, and represses the transcription of genes involved in iron uptake.…”

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confidence: 99%

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Catalase (KatA) and Alkyl Hydroperoxide Reductase (AhpC) Have Compensatory Roles in Peroxide Stress Resistance and Are Required for Survival, Persistence, and Nasal Colonization inStaphylococcus aureus

et al. 2007

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Oxidative-stress resistance in Staphylococcus aureus is linked to metal ion homeostasis via several interacting regulators. In particular, PerR controls the expression of a regulon of genes, many of which encode antioxidants. Two PerR regulon members, ahpC (alkylhydroperoxide reductase) and katA (catalase), show compensatory regulation, with independent and linked functions. An ahpC mutation leads to increased H 2 O 2 resistance due to greater katA expression via relief of PerR repression. Moreover, AhpC provides residual catalase activity present in a katA mutant. Mutation of both katA and ahpC leads to a severe growth defect under aerobic conditions in defined media (attributable to lack of catalase activity). This results in the inability to scavenge exogenous or endogenously produced H 2 O 2 , resulting in accumulation of H 2 O 2 in the medium. This leads to DNA damage, the likely cause of the growth defect. Surprisingly, the katA ahpC mutant is not attenuated in two independent models of infection, which implies reduced oxygen availability during infection. In contrast, both AhpC and KatA are required for environmental persistence (desiccation) and nasal colonization. Thus, oxidative-stress resistance is an important factor in the ability of S. aureus to persist in the hospital environment and so contribute to the spread of human disease.

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Section: Discussionmentioning

confidence: 99%

Section: Vol 189 2007 Peroxide Stress Resistance Proteins Of S Aurmentioning

confidence: 99%

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confidence: 99%

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Catalase (KatA) and Alkyl Hydroperoxide Reductase (AhpC) Have Compensatory Roles in Peroxide Stress Resistance and Are Required for Survival, Persistence, and Nasal Colonization inStaphylococcus aureus

et al. 2007

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“…B. subtilis peptidoglycan was purified as described (4) and digested overnight with the recombinant amidase domain of Atl (see SI Text) (37). Glycan was purified from the resulting soluble material by using a MonoS ion exchange chromatography column, as described (see SI Text) (6), concentrated three times by using SpeedVac, and applied to a TSKgelSW4000 size exclusion HPLC column (Tosoh).…”

Section: Methodsmentioning

confidence: 99%

Cell wall peptidoglycan architecture in Bacillus subtilis

Hayhurst

Kailas

Hobbs

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

217

227

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The bacterial cell wall is essential for viability and shape determination. Cell wall structural dynamics allowing growth and division, while maintaining integrity is a basic problem governing the life of bacteria. The polymer peptidoglycan is the main structural component for most bacteria and is made up of glycan strands that are cross-linked by peptide side chains. Despite study and speculation over many years, peptidoglycan architecture has remained largely elusive. Here, we show that the model rod-shaped bacterium Bacillus subtilis has glycan strands up to 5 m, longer than the cell itself and 50 times longer than previously proposed. Atomic force microscopy revealed the glycan strands to be part of a peptidoglycan architecture allowing cell growth and division. The inner surface of the cell wall has a regular macrostructure with Ϸ50 nm-wide peptidoglycan cables [average 53 ؎ 12 nm (n ‫؍‬ 91)] running basically across the short axis of the cell. Cross striations with an average periodicity of 25 ؎ 9 nm (n ‫؍‬ 96) along each cable are also present. The fundamental cabling architecture is also maintained during septal development as part of cell division. We propose a coiled-coil model for peptidoglycan architecture encompassing our data and recent evidence concerning the biosynthetic machinery for this essential polymer.

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“…A Spa mutant often is used in vitro, especially whenever secondary antibody-detection methods are used. It has been assumed that the effect(s) of antibody in vivo would be negated similarly by Spa, but antibody-mediated protection has been demonstrated against nasal colonization with Spa-sufficient strains (31,36). Passive i.p.…”

Section: Discussionmentioning

confidence: 99%

Protection from the acquisition of Staphylococcus aureus nasal carriage by cross-reactive antibody to a pneumococcal dehydrogenase

Lijek

Luque

Liu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Nasal colonization by Staphylococcus aureus is the major risk factor for disease and transmission. Epidemiological studies have reported a reduced risk of S. aureus carriage in immunocompetent but not in immunocompromised children colonized by Streptococcus pneumoniae. We investigate the hypothesis that the immune response to pneumococcal colonization affects S. aureus colonization. We demonstrate that pneumococcal colonization in mice inhibits subsequent S. aureus acquisition in an antibody-dependent manner and elicits antibody that cross-reacts with S. aureus. We identify the staphylococcal target of cross-reactive antibody as 1-pyrroline-5-carboxylate dehydrogenase (P5CDH), and the homologous immunogen in S. pneumoniae as SP_1119, both of which are conserved dehydrogenases. These antigens are necessary and sufficient to inhibit the acquisition of S. aureus colonization in a mouse model. Our findings demonstrate that immune-mediated cross-reactivity between S. pneumoniae and S. aureus protects against S. aureus nasal acquisition and thus reveal a paradigm for identifying protective antigens against S. aureus.pneumococcus | methicillin-resistant S. aureus | vaccine T he Gram-positive bacterial pathogen Staphylococcus aureus is responsible for significant morbidity, mortality, and excess healthcare costs worldwide. The management of S. aureus disease has become increasingly difficult because of the rising prevalence of methicillin-resistant S. aureus (MRSA), which can account for 60% of S. aureus infections in hospital and community settings (1, 2). Given the limited treatment options for MRSA infection, novel preventative approaches are needed to protect against S. aureus infection and transmission.A predominant risk factor for S. aureus infection and transmission is asymptomatic colonization of the anterior nares (3). Eighty percent of S. aureus invasive infections in humans are caused by the host's colonizing strain (4). However, the specific host and bacterial determinants of S. aureus nasal carriage are not well understood (5). In children, significantly reduced S. aureus colonization rates have been associated with carriage of another member of the upper respiratory tract flora, Streptococcus pneumoniae (6-14). These large and geographically diverse cohorts have demonstrated reproducibly that colonization with S. pneumoniae reduces the risk of S. aureus carriage by approximately half. This interference phenomenon has been reported for both vaccine and nonvaccine serotypes of S. pneumoniae (13). Moreover, pneumococcal vaccination, which reduces S. pneumoniae carriage, has been associated with an increased incidence of S. aureusinduced otitis media in children (15).The etiology of this interference phenomenon between S. pneumoniae and S. aureus colonization is unknown. Although in vitro studies have demonstrated that hydrogen peroxide secreted by S. pneumoniae is bactericidal to S. aureus in coculture (16-18), neither hydrogen peroxide secretion by S. pneumoniae nor hydrogen peroxide sensitivity of S. aureus...

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Identification of In Vivo–Expressed Antigens ofStaphylococcus aureusand Their Use in Vaccinations for Protection against Nasal Carriage

Cited by 185 publications

References 44 publications

Catalase (KatA) and Alkyl Hydroperoxide Reductase (AhpC) Have Compensatory Roles in Peroxide Stress Resistance and Are Required for Survival, Persistence, and Nasal Colonization inStaphylococcus aureus

Catalase (KatA) and Alkyl Hydroperoxide Reductase (AhpC) Have Compensatory Roles in Peroxide Stress Resistance and Are Required for Survival, Persistence, and Nasal Colonization inStaphylococcus aureus

Cell wall peptidoglycan architecture in Bacillus subtilis

Protection from the acquisition of Staphylococcus aureus nasal carriage by cross-reactive antibody to a pneumococcal dehydrogenase

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