No evident association of nasal carriage of Staphylococcus aureus or its small-colony variants with cotrimoxazole use or ANCA-associated vasculitis relapses

AbstractObjectiveTo identify the role of Staphylococcus aureus (SA) or its intracellular small-colony variant phenotype (SCV) with co-trimoxazole (CTX) or ANCA-associated vasculitis (AAV) activity.MethodsAll consecutive AAV patients with granulomatosis with polyangiitis (GPA), eosinophilic GPA or microscopic polyangiitis, followed at the French National Vasculitis Referral Center (09/2012–05/2013), and hospitalized non-AAV controls, exclusively for SA/SCV carriage comparisons, were enrolled. All had bilateral anterior nasal swab cultures. Nasal SA or SCV carriage was determined and associations with relapse(s), BVAS, ANCA-positivity, anti-staphylococcal and immunosuppressant use, were analysed ⩾4 years post-inclusion.ResultsNasal SA carriage rates did not differ among AAVs (P = 0.53): GPA (24/80; 30%), EGPA (7/28; 25%) and microscopic polyangiitis (3/11; 27.3%); and the rate was less frequent in controls than in GPA patients not taking CTX (P = 0.04). AAV patients taking CTX prophylaxis had less nasal SA carriage (8.7% vs 36.2%; P = 0.02). Nasal SA carriage or CTX use did not modify relapse rates, BVAS or ANCA-positivity at inclusion or during follow-up. Nasal SCV carriage, found in 15/207 (7.2%) patients, was similar for GPA (10/24; 41.7%), microscopic polyangiitis (2/7; 28.6%) and eosinophilic GPA (2/3; 66.7%), but higher (P = 0.02) than controls (1/14; 7.1%). SCV carriage by AAV groups did not modify relapse rates or ANCA positivity at inclusion or during follow-up; a trend towards higher BVAS was observed only for anti-PR3 ANCA patients.ConclusionNasal SA or SCV carriage was comparable among AAVs but more frequent than in controls. Nasal SA or SCV carriage and CTX use did not modify AAV relapse rates.

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Enhanced production of exopolysaccharide matrix and biofilm by a menadione-auxotrophic Staphylococcus aureus small-colony variant

Journal of Medical Microbiology ◽

10.1099/jmm.0.017046-0 ◽

2010 ◽

Vol 59 (5) ◽

pp. 521-527 ◽

Cited By ~ 36

Author(s):

Rachna Singh ◽

Pallab Ray ◽

Anindita Das ◽

Meera Sharma

Keyword(s):

Staphylococcus Aureus ◽

Tricarboxylic Acid Cycle ◽

Surface Hydrophobicity ◽

Tricarboxylic Acid ◽

Polysaccharide Intercellular Adhesin ◽

Wild Type ◽

Small Colony Variant ◽

Enhanced Production ◽

Small Colony

The role of Staphylococcus aureus small-colony variants (SCVs) in the pathogenesis of biofilm-associated infections remains unclear. This study investigated the mechanism behind increased biofilm-forming potential of a menadione-auxotrophic Staphylococcus aureus SCV compared with the wild-type parental strain, as recently reported by our laboratory. SCVs displayed an autoaggregative phenotype, with a greater amount of polysaccharide intercellular adhesin (PIA), significantly reduced tricarboxylic acid cycle activity and a decreased susceptibility to aminoglycosides and cell-wall inhibitors compared with wild-type. The biofilms formed by the SCV were highly structured, consisting of large microcolonies separated by channels, and contained more biomass as well as significantly more PIA than wild-type biofilms. The surface hydrophobicity of the two phenotypes was similar. Thus, the autoaggregation and increased biofilm-forming capacity of menadione-auxotrophic Staphylococcus aureus SCVs in this study was related to the enhanced production of PIA in these variants.

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Evolution of Staphylococcus aureus under Vancomycin Selective Pressure: the Role of the Small-Colony Variant Phenotype

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04508-14 ◽

2014 ◽

Vol 59 (2) ◽

pp. 1347-1351 ◽

Cited By ~ 14

Author(s):

Justin R. Lenhard ◽

Christof von Eiff ◽

Irene S. Hong ◽

Patricia N. Holden ◽

Michael D. Bear ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Therapy ◽

Selective Pressure ◽

Type Model ◽

Methicillin Resistant ◽

Small Colony Variants ◽

Content Type ◽

Small Colony Variant ◽

Small Colony

ABSTRACTStaphylococcus aureussmall-colony variants (SCVs) often persist despite antibiotic therapy. Against a 108-CFU/ml methicillin-resistantS. aureus(MRSA) (strain COL) population of which 0%, 1%, 10%, 50%, or 100% was an isogenichemBknockout (Ia48) subpopulation displaying the SCV phenotype, vancomycin achieved maximal reductions of 4.99, 5.39, 4.50, 3.28, and 1.66 log10CFU/ml over 48 h. Vancomycin at ≥16 mg/liter shifted a population from 50% SCV cells at 0 h to 100% SCV cells at 48 h, which was well characterized by a Hill-type model (R2> 0.90).

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The MpsB protein contributes to both the toxicity and immune evasion capacity of Staphylococcus aureus

Microbiology ◽

10.1099/mic.0.001096 ◽

2021 ◽

Vol 167 (10) ◽

Author(s):

Edward J. A. Douglas ◽

Seána Duggan ◽

Tarcisio Brignoli ◽

Ruth C. Massey

Keyword(s):

Staphylococcus Aureus ◽

Immune Evasion ◽

Type Species ◽

Severe Disease ◽

Toxin Production ◽

Content Type ◽

Small Colony Variant ◽

Link Type ◽

Small Colony

Understanding the role specific bacterial factors play in the development of severe disease in humans is critical if new approaches to tackle such infections are to be developed. In this study we focus on genes we have found to be associated with patient outcome following bacteraemia caused by the major human pathogen Staphylococcus aureus . By examining the contribution these genes make to the ability of the bacteria to survive exposure to the antibacterial factors found in serum, we identify three novel serum resistance-associated genes, mdeA, mpsB and yycH. Detailed analysis of an MpsB mutant supports its previous association with the slow growing small colony variant (SCV) phenotype of S. aureus , and we demonstrate that the effect this mutation has on membrane potential prevents the activation of the Agr quorum sensing system, and as a consequence the mutant bacteria do not produce cytolytic toxins. Given the importance of both toxin production and immune evasion for the ability of S. aureus to cause disease, we believe that these findings explain the role of the mpsB gene as a mortality-associated locus during human disease.

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In Vitro Activity of the Bacteriophage Endolysin HY-133 against Staphylococcus aureus Small-Colony Variants and Their Corresponding Wild Types

International Journal of Molecular Sciences ◽

10.3390/ijms20030716 ◽

2019 ◽

Vol 20 (3) ◽

pp. 716 ◽

Cited By ~ 3

Author(s):

Nina Schleimer ◽

Ursula Kaspar ◽

Dennis Knaack ◽

Christof von Eiff ◽

Sonja Molinaro ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Treatment Options ◽

Nasal Carriage ◽

Resistance Mechanisms ◽

Resistance Pattern ◽

Small Colony Variant ◽

Small Colony ◽

Time Kill ◽

Bacteriophage Endolysin

Nasal carriage of methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) represents both a source and a risk factor for subsequent infections. However, existing MRSA decolonization strategies and antibiotic treatment options are hampered by the duration of administration and particularly by the emergence of resistance. Moreover, beyond classical resistance mechanisms, functional resistance as the formation of the small-colony variant (SCV) phenotype may also impair the course and treatment of S. aureus infections. For the recombinant bacteriophage endolysin HY-133, rapid bactericidal and highly selective in vitro activities against MSSA and MRSA has been shown. In order to assess the in vitro efficacy of HY-133 against the SCV phenotype, minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) were evaluated on clinical SCVs, their isogenic wild types, as well as on genetically derived and gentamicin-selected SCVs. For all strains and growth phases, HY-133 MIC and MBC ranged between 0.12 and 1 mg/L. Time-kill studies revealed a fast-acting bactericidal activity of HY-133 resulting in a ≥3 − log10 decrease in CFU/mL within 1 h compared to oxacillin, which required 4–24 h. Since the mode of action of HY-133 was independent of growth phase, resistance pattern, and phenotype, it is a promising candidate for future S. aureus decolonization strategies comprising rapid activity against phenotypic variants exhibiting functional resistance.

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Staphylococcus aureus Carriage in Hidradenitis Suppurativa: Impact on Response to Adalimumab

Dermatology ◽

10.1159/000512617 ◽

2021 ◽

pp. 1-6

Author(s):

Dimitra Stergianou ◽

Vassiliki Tzanetakou ◽

Maria Argyropoulou ◽

Theodora Kanni ◽

Pantelis G. Bagos ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Clinical Response ◽

Odds Ratio ◽

Hidradenitis Suppurativa ◽

Positive Culture ◽

Nasal Carriage ◽

Loss Of Response ◽

Response Score ◽

Stimulation Of

Background: Several patients with hidradenitis suppurativa (HS) present flare-ups during treatment with adalimumab (ADA), the cause of which is not clear. ADA is the only FDA-approved biologic for the therapy of moderate-to-severe HS. A previous study of our group has shown that Staphylococcus aureus stimulation of whole blood affects the production of human β-defensin 2 and modulates HS severity. It is, therefore, hypothesized, that carriage of S. aureus may drive HS flare-ups. Objective: To explore the association between carriage of S. aureus and loss of response to ADA. Patients and Methods: Among patients with moderate-to-severe HS without carriage of S. aureus at start of treatment with ADA, we investigated for carriage of S. aureus from the nares when flare-ups occurred. Flare-ups were pre-defined as at least 25% increase of inflammatory lesions (sum of inflammatory nodules and abscesses) from baseline. Samplings were also done after completion of 12 weeks of ADA treatment from all patients who did not present flare-ups. Clinical response to ADA was assessed by the HS Clinical Response score (HiSCR). Results: Thirty-nine patients were studied; 24 with Hurley II stage HS and 15 with Hurley III stage HS. Twenty-nine patients achieved HiSCR after 12 weeks of treatment without any flare-ups; 10 patients had flare-ups and failed HiSCR. Three (10.3%) and 5 (50%) patients, respectively, had nasal carriage of S. aureus (odds ratio 8.67; 95% CI 1.54–48.49; p = 0.014). Among 32 patients reaching follow-up week 48, 20 patients achieved HiSCR and 12 had flare-ups leading to ADA failure; 2 (10%) and 5 (41.7%) patients, respectively, had positive culture for S. aureus (odds ratio 6.42; 95% CI 1.00–41.20; p = 0.05). Conclusion: Nasal carriage of S. aureus may be associated with loss of response to ADA. Findings need confirmation in larger series of patients.

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A Narrative Review of Early Oral Stepdown Therapy for the Treatment of Uncomplicated Staphylococcus aureus Bacteremia: Yay or Nay?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa151 ◽

2020 ◽

Vol 7 (6) ◽

Author(s):

Michael Dagher ◽

Vance G Fowler ◽

Patty W Wright ◽

Milner B Staub

Keyword(s):

Staphylococcus Aureus ◽

Hospital Readmission ◽

Potential Role ◽

Review Article ◽

Narrative Review ◽

Oral Antibiotics ◽

Staphylococcus Aureus Bacteremia ◽

Complete Treatment

Abstract Historically, intravenous (IV) antibiotics have been the cornerstone of treatment for uncomplicated Staphylococcus aureus bacteremia (SAB). However, IV antibiotics are expensive, increase the rates of hospital readmission, and can be associated with catheter-related complications. As a result, the potential role of oral antibiotics in the treatment of uncomplicated SAB has become a subject of interest. This narrative review article aims to summarize key arguments for and against the use of oral antibiotics to complete treatment of uncomplicated SAB and evaluates the available evidence for specific oral regimens. We conclude that evidence suggests that oral step-down therapy can be an alternative for select patients who meet the criteria for uncomplicated SAB and will comply with medical treatment and outpatient follow-up. Of the currently studied regimens discussed in this article, linezolid has the most support, followed by fluoroquinolone plus rifampin.

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Increased Expression of Clumping Factor and Fibronectin-Binding Proteins by hemB Mutants of Staphylococcus aureus Expressing Small Colony Variant Phenotypes

Infection and Immunity ◽

10.1128/iai.70.10.5428-5437.2002 ◽

2002 ◽

Vol 70 (10) ◽

pp. 5428-5437 ◽

Cited By ~ 120

Author(s):

Pierre Vaudaux ◽

Patrice Francois ◽

Carmelo Bisognano ◽

William L. Kelley ◽

Daniel P. Lew ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Surface Display ◽

Human Embryonic Kidney Cells ◽

Small Colony Variant ◽

Reverse Transcription Pcr ◽

Bacterial Adhesins ◽

Transport Chain ◽

Complete Restoration ◽

Small Colony ◽

Slow Growing

ABSTRACT Small colony variants (SCVs) of Staphylococcus aureus are slow-growing subpopulations that cause persistent and relapsing infections. The altered phenotype of SCV can arise from defects in menadione or hemin biosynthesis, which disrupt the electron transport chain and decrease ATP concentrations. With SCVs, virulence is altered by a decrease in exotoxin production and susceptibility to various antibiotics, allowing their intracellular survival. The expression of bacterial adhesins by SCVs is poorly documented. We tested fibrinogen- and fibronectin-mediated adhesion of a hemB mutant of S. aureus 8325-4 that is defective for hemin biosynthesis and exhibits a complete SCV phenotype. In this strain, adhesion to fibrinogen and fibronectin was significantly higher than that of its isogenic, normally growing parent and correlated with the increased surface display of these adhesins as assessed by flow cytometry. Real-time quantitative reverse transcription-PCR demonstrated increased expression of clfA and fnb genes by the hemB mutant compared to its isogenic parent. The influence of the hemB mutation on altered adhesin expression was confirmed by showing complete restoration of the wild-type adhesive phenotype in the hemB mutant, either by complementing with intact hemB or by supplementing the growth medium with hemin. Increased surface display of fibrinogen and fibronectin adhesins by the hemB mutation occurred independently from agr, a major regulatory locus of virulence factors in S. aureus. Both agr-positive and agr-lacking hemB mutants were also more efficiently internalized by human embryonic kidney cells than were their isogenic controls, presumably because of increased surface display of their fibronectin adhesins.

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