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

2010 ◽  
Vol 59 (5) ◽  
pp. 521-527 ◽  
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.

scholarly journals Enhanced Post-Stationary-Phase Survival of a Clinical Thymidine-Dependent Small-Colony Variant of Staphylococcus aureus Results from Lack of a Functional Tricarboxylic Acid Cycle

2007 ◽  
Vol 189 (7) ◽  
pp. 2936-2940 ◽  
Author(s):  
Indranil Chatterjee ◽  
Mathias Herrmann ◽  
Richard A. Proctor ◽  
Georg Peters ◽  
Barbara C. Kahl
Keyword(s):  
Staphylococcus Aureus ◽  
Acetic Acid ◽  
Acid Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Altered Expression ◽  
Acid Cycle ◽  
Small Colony Variant ◽  
Stationary Phase Survival ◽  
Small Colony

ABSTRACT The mechanisms underlying the persistence of the Staphylococcus aureus small-colony variant (SCV) are not fully elucidated. In this study, clinical thymidine-dependent SCVs displayed altered expression of citB, clpC, and arcA genes, reduced acetate catabolization, and enhanced survival. These results implicate the importance of changes in tricarboxylic acid cycle and acetic acid metabolism in SCV survival and persistence.

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

Rheumatology ◽  
2019 ◽  
Vol 59 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Boun Kim Tan ◽  
Yoann Crabol ◽  
Jason Tasse ◽  
Frédéric Laurent ◽  
Narimane Nekkab ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Nasal Swab ◽  
Microscopic Polyangiitis ◽  
Nasal Carriage ◽  
Small Colony Variant ◽  
Anca Associated Vasculitis ◽  
Small Colony ◽  
Relapse Rates

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.

scholarly journals Influence of the Protein Kinase C Activator Phorbol Myristate Acetate on the Intracellular Activity of Antibiotics against Hemin- and Menadione-Auxotrophic Small-Colony Variant Mutants of Staphylococcus aureus and Their Wild-Type Parental Strain in Human THP-1 Cells

2012 ◽  
Vol 56 (12) ◽  
pp. 6166-6174 ◽  
Author(s):  
Laetitia G. Garcia ◽  
Sandrine Lemaire ◽  
Barbara C. Kahl ◽  
Karsten Becker ◽  
Richard A. Proctor ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Parental Strain ◽  
Wild Type ◽  
Content Type ◽  
Small Colony Variant ◽  
Intracellular Activity ◽  
Kinase C ◽  
Pharmacodynamic Profile ◽  
Small Colony ◽  
Intracellular Fate

ABSTRACTIn a previous study (L. G. Garcia et al., Antimicrob. Agents Chemother. 56:3700–3711, 2012), we evaluated the intracellular fate ofmenDandhemBmutants (corresponding to menadione- and hemin-dependent small-colony variants, respectively) of the parental COL methicillin-resistantStaphylococcus aureusstrain and the pharmacodynamic profile of the intracellular activity of a series of antibiotics in human THP-1 monocytes. We have now examined the phagocytosis and intracellular persistence of the same strains in THP-1 cells activated by phorbol 12-myristate 13-acetate (PMA) and measured the intracellular activity of gentamicin, moxifloxacin, and oritavancin in these cells. Postphagocytosis intracellular counts and intracellular survival were lower in PMA-activated cells, probably due to their higher killing capacities. Gentamicin and moxifloxacin showed a 5- to 7-fold higher potency (lower static concentrations) against the parental strain, itshemBmutant, and the genetically complemented strain in PMA-activated cells and against themenDstrain in both activated and nonactivated cells. This effect was inhibited when cells were incubated withN-acetylcysteine (a scavenger of oxidant species). In parallel, we observed that the MICs of these drugs were markedly reduced if bacteria had been preexposed to H2O2. In contrast, the intracellular potency of oritavancin was not different in activated and nonactivated cells and was not decreased by the addition ofN-acetylcysteine, regardless of the phenotype of the strains. The oritavancin MIC was also unaffected by preincubation of the bacteria with H2O2. Thus, activation of THP-1 cells by PMA may increase the intracellular potency of certain antibiotics (probably due to synergy with reactive oxygen species), but this effect cannot be generalized to all antibiotics.

scholarly journals Phenotypic Stability of Staphylococcus aureus Small Colony Variants (SCV) Isolates from Cystic Fibrosis (CF) Patients

2019 ◽  
Vol 16 (11) ◽  
pp. 1940 ◽  
Author(s):  
Clemens Kittinger ◽  
Daniela Toplitsch ◽  
Bettina Folli ◽  
Lilian Masoud Landgraf ◽  
Gernot Zarfel
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Point Mutations ◽  
High Variability ◽  
Wild Type ◽  
Phenotypic Stability ◽  
Small Colony Variant ◽  
Gene Coding ◽  
Wild Type Phenotype ◽  
Small Colony

One of the most interesting features of Staphylococcus aureus is its ability to switch to a small colony variant (SCV). This switch allows the pathogen to survive periods of antibiotic treatment or pressure from the immune system of the host and further enables it to start the infection once again after the environmental stress declines. However, so far only little is known about this reversion back to the more virulent wild type phenotype. Therefore, this study aimed to analyze the frequency of reversion to the wild type phenotype of thymidine auxotroph S. aureus SCV isolates (TD-SCVs) obtained from patients with cystic fibrosis (CF). With the use of single cell starting cultures, the occurrence of the thymidine prototroph revertants was monitored. The underlying mutational cause of the SCVs and subsequent revertants were analyzed by sequencing the gene coding for thymidylate synthase (ThyA), whose mutations are known to produce thymidine auxotroph S. aureus SCV. In our study, the underlying mutational cause for the switch to the TD-SCV phenotype was primarily point mutations. Out of twelve isolates, seven isolates showed an occurrence of revertants with a frequency ranging from 90.06% to 0.16%. This high variability in the frequency of reversion to the wild type was not expected. However, this variability in the frequency of reversion may also be the key to successful re-infection of the host. Sometimes quick reversion to the wild type proves necessary for survival, whereas other times, staying hidden for a bit longer leads to success in re-colonization of the host.

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

2014 ◽  
Vol 59 (2) ◽  
pp. 1347-1351 ◽  
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).

scholarly journals The Endospore-Forming Pathogen Bacillus cereus Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Elrike Frenzel ◽  
Markus Kranzler ◽  
Timo D. Stark ◽  
Thomas Hofmann ◽  
Monika Ehling-Schulz
Keyword(s):  
Antibiotic Resistance ◽  
Bacillus Cereus ◽  
Differential Diagnostics ◽  
Wild Type ◽  
Content Type ◽  
Small Colony Variant ◽  
Enhanced Production ◽  
Small Colony ◽  
First Time ◽  
Slow Growing

ABSTRACTBacillus cereusis among the microorganisms most often isolated from cases of food spoilage and causes gastrointestinal diseases as well as nongastrointestinal infections elicited by the emetic toxin cereulide, enterotoxins, and a panel of tissue-destructive virulence factors. This opportunistic pathogen is increasingly associated with rapidly fatal clinical infections especially linked to neonates and immunocompromised individuals. Fatality results from either the misdiagnosis ofB. cereusas a contaminant of the clinical specimen or from failure of antibiotic therapy. Here we report for the first time that exposure to aminoglycoside antibiotics induces a phenotype switching of emeticB. cereussubpopulations to a slow-growing small colony variant (SCV) state. Along with altered antibiotic resistance, SCVs showed distinct phenotypic and metabolic properties, bearing the risk of antibiotic treatment failure and of clinical misdiagnosis by standard identification tests used in routine diagnostic. The SCV subpopulation is characterized by enhanced production of the toxin cereulide, but it does not secrete tissue-destructive and immune system-affecting enzymes such as sphingomyelinase and phospholipase. SCVs showed significantly prolonged persistence and decreased virulence in theGalleria mellonellamodel for bacterial infections, indicating diversification concerning their ecological lifestyle. Importantly, diversification into coexisting wild-type and SCV subpopulations also emerged during amikacin pressure duringin vivoinfection experiments.IMPORTANCEThis study shows for the first time that pathogenic spore-formingB. cereusstrains are able to switch to a so far unreported slow-growing lifestyle, which differs substantially in terms of developmental, phenotypic, metabolic, and virulence traits from the wild-type populations. This underpins the necessity of molecular-based differential diagnostics and a well-chosen therapeutic treatment strategy in clinical environments to combatB. cereusin a tailored manner. The reported induction of SCV in an endospore-forming human pathogen requires further research to broaden our understanding of a yet unexplored antibiotic resistance mechanism in sporulating bacteria. Our work also raises a general question about the ecological meaning of SCV subpopulation emergence and importance of SCV in sporeformer populations as an alternative route, next to sporulation, to cope with stresses encountered in natural niches, such as soil or host interfaces.

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

Microbiology ◽  
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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