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1.
Biochim Biophys Acta Mol Basis Dis ; 1865(10): 2657-2670, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31299217

ABSTRACT

Staphylococcus aureus is the most prominent cause of skin and soft tissue infections (SSTI) worldwide. Mortality associated with invasive SSTI is a major threat to public health considering the incidence of antibiotic resistant isolates in particular methicillin resistant S. aureus both in the hospital (HA-MRSA) and in the community (CA-MRSA). To overcome the increasing difficulties in the clinical management of SSTI due to MRSA, new prophylactic and therapeutic approaches are urgently needed and a preventive vaccine would be welcome. The rational design of an anti-S. aureus vaccine requires a deep knowledge of the role that the different bacterial virulence factors play according to the type of infection. In the present study, using a set of isogenic deficient mutants and their complemented strains we determined that the staphylococcal surface proteins SpA and Sbi play an important role in the induction of inflammatory cytokines and chemokines in the skin during SSTI. SpA and Sbi initiate signaling cascades that lead to the early recruitment of neutrophils, modulate their lifespan in the skin milieu and contribute to proper abscess formation and bacterial eradication. Moreover, the expression of SpA and Sbi appear critical for skin repair and wound healing. Thus, these results indicate that SpA and Sbi can promote immune responses in the skin that are beneficial for the host and therefore, should not be neutralized with vaccine formulations designed to prevent SSTI.


Subject(s)
Abscess/immunology , Antigens, Bacterial/metabolism , Bacterial Proteins/metabolism , Carrier Proteins/metabolism , Skin/immunology , Soft Tissue Infections/metabolism , Staphylococcal Infections/metabolism , Staphylococcus aureus/metabolism , Wound Healing/physiology , Abscess/metabolism , Abscess/microbiology , Animals , Chemokines/metabolism , Cytokines/metabolism , Disease Models, Animal , Humans , Keratinocytes , Methicillin-Resistant Staphylococcus aureus/metabolism , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Skin/microbiology , Skin/pathology , Soft Tissue Infections/immunology , Soft Tissue Infections/microbiology , Soft Tissue Infections/pathology , Staphylococcal Infections/immunology , Staphylococcus aureus/pathogenicity
2.
PLoS One ; 8(10): e76108, 2013.
Article in English | MEDLINE | ID: mdl-24143178

ABSTRACT

Analysis of the metaproteome of microbial communities is important to provide an insight of community physiology and pathogenicity. This study evaluated the metaproteome of endodontic infections associated with acute apical abscesses and asymptomatic apical periodontitis lesions. Proteins persisting or expressed after root canal treatment were also evaluated. Finally, human proteins associated with these infections were identified. Samples were taken from root canals of teeth with asymptomatic apical periodontitis before and after chemomechanical treatment using either NaOCl or chlorhexidine as the irrigant. Samples from abscesses were taken by aspiration of the purulent exudate. Clinical samples were processed for analysis of the exoproteome by using two complementary mass spectrometry platforms: nanoflow liquid chromatography coupled with linear ion trap quadrupole Velos Orbitrap and liquid chromatography-quadrupole time-of-flight. A total of 308 proteins of microbial origin were identified. The number of proteins in abscesses was higher than in asymptomatic cases. In canals irrigated with chlorhexidine, the number of identified proteins decreased substantially, while in the NaOCl group the number of proteins increased. The large majority of microbial proteins found in endodontic samples were related to metabolic and housekeeping processes, including protein synthesis, energy metabolism and DNA processes. Moreover, several other proteins related to pathogenicity and resistance/survival were found, including proteins involved with adhesion, biofilm formation and antibiotic resistance, stress proteins, exotoxins, invasins, proteases and endopeptidases (mostly in abscesses), and an archaeal protein linked to methane production. The majority of human proteins detected were related to cellular processes and metabolism, as well as immune defense. Interrogation of the metaproteome of endodontic microbial communities provides information on the physiology and pathogenicity of the community at the time of sampling. There is a growing need for expanded and more curated protein databases that permit more accurate identifications of proteins in metaproteomic studies.


Subject(s)
Abscess/metabolism , Endodontics , Periapical Periodontitis/metabolism , Proteomics , Abscess/microbiology , Adult , Asymptomatic Diseases , Humans , Periapical Periodontitis/microbiology , Young Adult
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