scholarly journals Analysis of Staphylococcus aureus transcriptome in pediatric soft tissue abscesses and comparison to murine infections

2021 ◽  
Author(s):  
K Moffitt ◽  
E Cheung ◽  
T Yeung ◽  
C Stamoulis ◽  
R Malley
Keyword(s):  
Staphylococcus Aureus ◽  
Soft Tissue ◽  
Ex Vivo ◽  
Human Infection ◽  
Nucleic Acid Amplification ◽  
Clinical Strain ◽  
Nasal Colonization ◽  
Abscess Drainage ◽  
Mrna Transcripts

A comprehensive understanding of how Staphylococcus aureus adapts to cause infections in humans can inform development of diagnostic, therapeutic, and preventive approaches. Expression analysis of clinical strain libraries depicts in vitro conditions that differ from those in human infection, but low bacterial burden and the requirement for reverse transcription or nucleic acid amplification complicate such analyses of bacteria causing human infection. We developed methods to evaluate the mRNA transcript signature of S. aureus in pediatric skin and soft tissue (SSTI) infections directly ex vivo. Abscess drainage from 47 healthy pediatric patients undergoing drainage of a soft tissue infection was collected, and RNA was extracted from samples from patients with microbiologically confirmed S. aureus abscesses (42% due to methicillin-resistant S. aureus, MRSA). Using the Nanostring platform and primers targeting S. aureus mRNA transcripts encoding surface-expressed or secreted proteins, we measured direct counts of 188 S. aureus mRNA transcripts in abscess drainage. We further evaluated this mRNA signature in murine models of S. aureus SSTI and nasal colonization where the kinetics of the transcriptome could be determined. Heat maps of the S. aureus mRNA signatures from pediatric abscesses demonstrated consistent per target expression across patients. While there was significant overlap with the profiles from murine SSTI and nasal colonization, important differences were noted, which can inform efforts to develop therapeutic and vaccine approaches.

scholarly journals Characterization of the Retrocyclin Analogue RC-101 as a Preventative of Staphylococcus aureus Nasal Colonization

2011 ◽  
Vol 55 (11) ◽  
pp. 5338-5346 ◽  
Author(s):  
Ryan P. Lamers ◽  
Colleen R. Eade ◽  
Alan J. Waring ◽  
Amy L. Cole ◽  
Alexander M. Cole
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Treatment Options ◽  
Nasal Colonization ◽  
Proinflammatory Response ◽  
Content Type ◽  
Bactericidal Effects ◽  
Prevention Of Nosocomial Infection

ABSTRACTNasal colonization ofStaphylococcus aureusis a risk factor for pathogenic autoinfection, particularly in postoperative patients and the immunocompromised. As such, standardized preoperative nasal decolonization ofS. aureushas become a major consideration for the prevention of nosocomial infection. However, only a few treatment options for nasal decolonization are currently available, with resistance to these approaches already a concern. Here we have identified the macrocyclic θ-defensin analogue RC-101 as a promising anti-S. aureusagent for nasal decolonization. RC-101 exhibits bactericidal effects againstS. aureuswith the use ofin vitroepithelium-free systems, while also preventing the pathogen's proliferation and attachment in anex vivohuman nasal epithelial cell adhesion model and an organotypic model of human airway epithelia. Peptide concentrations as low as 2.5 μM elicited significant reductions inS. aureusgrowth in epithelium-free systems, with 10 μM concentrations being completely bactericidal for all strains tested, including USA300. Inex vivonasal colonization models, RC-101 significantly reduced adherence, survival, and proliferation ofS. aureuson human nasal epithelia. Reductions inS. aureusviability were evident in these assays, with as little as 1 μg of peptide per tissue, while 10 μg of RC-101 completely prevented adhesion of all strains tested. Furthermore, RC-101 did not exhibit cellular toxicity to human nasal epithelia at concentrations up to 200 μM, nor did it induce a proinflammatory response in these cells. Collectively, the findings of this study identify RC-101 as a potential preventative ofS. aureusnasal colonization.

scholarly journals In Vitro and Ex Vivo Efficacy of Novel Trp-Arg Rich Analogue of α-MSH against Staphylococcus aureus

ACS Omega ◽  
2020 ◽  
Vol 5 (7) ◽  
pp. 3258-3270
Author(s):  
Jyotsna Singh ◽  
Sana Mumtaz ◽  
Seema Joshi ◽  
Kasturi Mukhopadhyay
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo

scholarly journals Antimicrobial and Antibiofilm Activity against Staphylococcus aureus of Opuntia ficus-indica (L.) Mill. Cladode Polyphenolic Extracts

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 117 ◽  
Author(s):  
Federica Blando ◽  
Rossella Russo ◽  
Carmine Negro ◽  
Luigi De Bellis ◽  
Stefania Frassinetti
Keyword(s):  
Staphylococcus Aureus ◽  
Antioxidant Activity ◽  
Antioxidant Capacity ◽  
Biofilm Formation ◽  
Ex Vivo ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Total Phenolic ◽  
Antibiofilm Activity ◽  
Opuntia Ficus Indica

Plant extracts are a rich source of natural compounds with antimicrobial properties, which are able to prevent, at some extent, the growth of foodborne pathogens. The aim of this study was to investigate the potential of polyphenolic extracts from cladodes of Opuntia ficus-indica (L.) Mill. to inhibit the growth of some enterobacteria and the biofilm formation by Staphylococcus aureus. Opuntia ficus-indica cladodes at two stages of development were analysed for total phenolic content and antioxidant activity by Oxygen Radical Absorbance Capacity (ORAC) and Trolox equivalent antioxidant capacity (TEAC) (in vitro assays) and by cellular antioxidant activity in red blood cells (CAA-RBC) (ex vivo assay). The Liquid Chromatography Time-of-Flight Mass Spectrometry (LC/MS–TOF) analysis of the polyphenolic extracts revealed high levels of piscidic acid, eucomic acid, isorhamnetin derivatives and rutin, particularly in the immature cladode extracts. Opuntia cladodes extracts showed a remarkable antioxidant activity (in vitro and ex vivo), a selective inhibition of the growth of Gram-positive bacteria, and an inhibition of Staphylococcus aureus biofilm formation. Our results suggest and confirm that Opuntia ficus-indica cladode extracts could be employed as functional food, due to the high polyphenolic content and antioxidant capacity, and used as natural additive for food process control and food safety.

scholarly journals Hydrogen Peroxide-Mediated Interference Competition by Streptococcus pneumoniae Has No Significant Effect on Staphylococcus aureus Nasal Colonization of Neonatal Rats

2008 ◽  
Vol 191 (2) ◽  
pp. 571-575 ◽  
Author(s):  
Elisa Margolis
Keyword(s):  
Hydrogen Peroxide ◽  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Interference Competition ◽  
Inhibitory Effect ◽  
Nasal Colonization ◽  
Neonatal Rats ◽  
Mixed Inoculum ◽  
Relative Scarcity

ABSTRACT It has been proposed that the relative scarcity of Staphylococcus aureus and Streptococcus pneumoniae cocolonization in the nasopharynxes of humans can be attributed to hydrogen peroxide-mediated interference competition. Previously it has been shown in vitro that H2O2 produced by S. pneumoniae is bactericidal to S. aureus. To ascertain whether H2O2 has this inhibitory effect in the nasal passages of neonatal rats, colonization experiments were performed with S. aureus and S. pneumoniae. The results of these experiments with neonatal rats are inconsistent with the hypothesis that hydrogen peroxide-mediated killing of S. aureus by S. pneumoniae is responsible for the relative scarcity of cocolonization by these bacteria. In mixed-inoculum colonization experiments and experiments where S. aureus invaded the nasopharynxes of rats with established S. pneumoniae populations, the density of S. aureus did not differ whether the S. pneumoniae strain was H2O2 secreting or non-H2O2 secreting (SpxB). Moreover, the advantage of catalase production by S. aureus in competition with a non-catalase-producing strain (KatA) during nasal colonization was no greater in the presence of H2O2-producing S. pneumoniae than in the presence of non-H2O2-producing S. pneumoniae.

scholarly journals Clumping Factor B Promotes Adherence of Staphylococcus aureus to Corneocytes in Atopic Dermatitis

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Orla M. Fleury ◽  
Maeve A. McAleer ◽  
Cécile Feuillie ◽  
Cécile Formosa-Dague ◽  
Emily Sansevere ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Clonal Complex ◽  
Ex Vivo ◽  
Nasal Carriage ◽  
Binding Activity ◽  
Clinical Strain ◽  
Healthy Children ◽  
Content Type ◽  
Force Microscopy

ABSTRACT Staphylococcus aureus skin infection is a frequent and recurrent problem in children with the common inflammatory skin disease atopic dermatitis (AD). S. aureus colonizes the skin of the majority of children with AD and exacerbates the disease. The first step during colonization and infection is bacterial adhesion to the cornified envelope of corneocytes in the outer layer, the stratum corneum. Corneocytes from AD skin are structurally different from corneocytes from normal healthy skin. The objective of this study was to identify bacterial proteins that promote the adherence of S. aureus to AD corneocytes. S. aureus strains from clonal complexes 1 and 8 were more frequently isolated from infected AD skin than from the nasal cavity of healthy children. AD strains had increased ClfB ligand binding activity compared to normal nasal carriage strains. Adherence of single S. aureus bacteria to corneocytes from AD patients ex vivo was studied using atomic force microscopy. Bacteria expressing ClfB recognized ligands distributed over the entire corneocyte surface. The ability of an isogenic ClfB-deficient mutant to adhere to AD corneocytes compared to that of its parent clonal complex 1 clinical strain was greatly reduced. ClfB from clonal complex 1 strains had a slightly higher binding affinity for its ligand than ClfB from strains from other clonal complexes. Our results provide new insights into the first step in the establishment of S. aureus colonization in AD patients. ClfB is a key adhesion molecule for the interaction of S. aureus with AD corneocytes and represents a target for intervention.

scholarly journals Emerging multidrug resistance in community-associated Staphylococcus aureus involved in skin and soft tissue infections and nasal colonization

2017 ◽  
Vol 72 (9) ◽  
pp. 2461-2468 ◽  
Author(s):  
Grace C. Lee ◽  
Steven D. Dallas ◽  
Yufeng Wang ◽  
Randall J. Olsen ◽  
Kenneth A. Lawson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Soft Tissue ◽  
Nasal Colonization ◽  
Soft Tissue Infections

scholarly journals A case of infection caused by the basidiomycete Phellinus undulatus

2011 ◽  
Vol 60 (2) ◽  
pp. 256-258 ◽  
Author(s):  
Deborah Williamson ◽  
Sushil Pandey ◽  
Susan Taylor ◽  
Karen Rogers ◽  
Louanne Storey ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Molecular Analysis ◽  
Soft Tissue Infection ◽  
Human Infection ◽  
Morphological Features ◽  
Tissue Infection

We present a case of soft tissue infection caused by the basidiomycete Phellinus undulatus. To our knowledge, this is the first reported case of human infection caused by this fungus. Definitive identification was only possible through molecular analysis as the isolate failed to produce any distinct morphological features in vitro.

scholarly journals Effect of Hochuekkito (Buzhongyiqitang) on Nasal Cavity Colonization of Methicillin-Resistant Staphylococcus aureus in Murine Model

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 83 ◽  
Author(s):  
Masaaki Minami ◽  
Toru Konishi ◽  
Toshiaki Makino
Keyword(s):  
Staphylococcus Aureus ◽  
Nasal Cavity ◽  
Murine Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Thymidine Uptake ◽  
Nasal Colonization ◽  
Immune Functions ◽  
Murine Splenocytes ◽  
Methicillin Resistant

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections are largely preceded by colonization with MRSA. Hochuekkito is the formula composing 10 herbal medicines in traditional Kampo medicine to treat infirmity and to stimulate immune functions. We evaluated the efficacy of hochuekkito extract (HET) against MRSA colonization using a nasal infection murine model. Methods: We evaluated the effects of HET as follows: (1) the growth inhibition by measuring turbidity of bacterial culture in vitro, (2) the nasal colonization of MRSA by measuring bacterial counts, and (3) the splenocyte proliferation in mice orally treated with HET by the 3H-thymidine uptake assay. Results: HET significant inhibited the growth of MRSA. The colony forming unit (CFU) in the nasal fluid of HET-treated mice was significantly lower than that of HET-untreated mice. When each single crude drug—Astragali radix, Bupleuri radix, Zingiberis rhizoma, and Cimicifugae rhizome—was removed from hochuekkito formula, the effect of the formula significantly weakened. The uptake of 3H-thymidine into murine splenocytes treated with HET was significantly higher than that from untreated mice. The effects of the modified formula described above were also significantly weaker than those of the original formula. Conclusions: Hochuekkito is effective for the treatment of MRSA nasal colonization in the murine model. We suggest HET as the therapeutic candidate for effective therapy on nasal cavity colonization of MRSA in humans.

scholarly journals A Putative Bacterial ABC Transporter Circumvents the Essentiality of Signal Peptidase

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
J. Hiroshi Morisaki ◽  
Peter A. Smith ◽  
Shailesh V. Date ◽  
Kimberly K. Kajihara ◽  
Chau Linda Truong ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Abc Transporter ◽  
Signal Peptide ◽  
Transcriptional Repressor ◽  
Signal Peptidase ◽  
Clinical Strain ◽  
Type I ◽  
Atpase Gene ◽  
Associated Proteins

ABSTRACT The type I signal peptidase of Staphylococcus aureus , SpsB, is an attractive antibacterial target because it is essential for viability and extracellularly accessible. We synthesized compound 103, a novel arylomycin-derived inhibitor of SpsB with significant potency against various clinical S. aureus strains (MIC of ~1 µg/ml). The predominant clinical strain USA300 developed spontaneous resistance to compound 103 with high frequency, resulting from single point mutations inside or immediately upstream of cro / cI , a homolog of the lambda phage transcriptional repressor cro . These cro / cI mutations led to marked (>50-fold) overexpression of three genes encoding a putative ABC transporter. Overexpression of this ABC transporter was both necessary and sufficient for resistance and, notably, circumvented the essentiality of SpsB during in vitro culture. Mutation of its predicted ATPase gene abolished resistance, suggesting a possible role for active transport; in these bacteria, resistance to compound 103 occurred with low frequency and through mutations in spsB . Bacteria overexpressing the ABC transporter and lacking SpsB were capable of secreting a subset of proteins that are normally cleaved by SpsB and instead were cleaved at a site distinct from the canonical signal peptide. These bacteria secreted reduced levels of virulence-associated proteins and were unable to establish infection in mice. This study reveals the mechanism of resistance to a novel arylomycin derivative and demonstrates that the nominal essentiality of the S. aureus signal peptidase can be circumvented by the upregulation of a putative ABC transporter in vitro but not in vivo . IMPORTANCE The type I signal peptidase of Staphylococcus aureus (SpsB) enables the secretion of numerous proteins by cleavage of the signal peptide. We synthesized an SpsB inhibitor with potent activity against various clinical S. aureus strains. The predominant S. aureus strain USA300 develops resistance to this inhibitor by mutations in a novel transcriptional repressor ( cro / cI ), causing overexpression of a putative ABC transporter. This mechanism promotes the cleavage and secretion of various proteins independently of SpsB and compensates for the requirement of SpsB for viability in vitro . However, bacteria overexpressing the ABC transporter and lacking SpsB secrete reduced levels of virulence-associated proteins and are unable to infect mice. This study describes a bacterial resistance mechanism that provides novel insights into the biology of bacterial secretion.

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