Characterization of CO<sub>2</sub>Dependent Microcolony Variants of<i>Staphylococcus aureus</i>

Slifkin, Malcolm; Merkow, Leonard P.; Kreuzberger, Sue A.; Engwall, Carol; Pardo, Matias

doi:10.1093/ajcp/56.5.584

Cited by 19 publications

(11 citation statements)

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“…Probably, any S. aureus strain belonging to any ST can develop SCV CO 2 auxotrophy, although we do not know what alterations in bacterial metabolism may cause this type of variant or the genetic mechanism for reversion to a rapidly growing form. In 1970 investigators who studied two strains of CO 2 -dependent microcolony variants of S. aureus by electron microscopy showed that the cell walls of the isolates when grown in air were thick and irregular (19). In contrast, in a CO 2 atmosphere, their ultrastructure appeared to be that of normal staphylococci.…”

Section: Discussionmentioning

confidence: 99%

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Clinical and Molecular Characteristics of Infections with CO ₂ -Dependent Small-Colony Variants of Staphylococcus aureus

et al. 2010

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Most Staphylococcus aureus small-colony variants (SCVs) are auxotrophs for menadione, hemin, or thymidine but rarely for CO 2 . We conducted a prospective investigation of all clinical cases of CO 2 -dependent S. aureus during a 3-year period. We found 14 CO 2 -dependent isolates of S. aureus from 14 patients that fulfilled all requirements to be considered SCVs, 9 of which were methicillin resistant. The clinical presentations included four cases of catheter-related bacteremia, one complicated by endocarditis; two deep infections (mediastinitis and spondylodiscitis); four wound infections; two respiratory infections; and two cases of nasal colonization. Pulsed-field gel electrophoresis typing showed that the 14 isolates were distributed into 4 types corresponding to sequence types ST125-agr group II (agrII), ST30-agrIII, ST34-agrIII, and ST45-agrI. An array hybridization technique performed on the 14 CO 2 -dependent isolates and 20 S. aureus isolates with normal phenotype and representing the same sequence types showed that all possessed the enterotoxin gene cluster egc, as well as the genes for ␣-hemolysin and ␦-hemolysin; biofilm genes icaA, icaC, and icaD; several microbial surface components recognizing adhesive matrix molecules (MSCRAMM) genes (clfA, clfB, ebh, eno, fib, ebpS, sdrC, and vw); and the isaB gene. Our study confirms the importance of CO 2 -dependent SCVs of S. aureus as significant pathogens. Clinical microbiologists should be aware of this kind of auxotrophy because recovery and identification are challenging and not routine. Further studies are necessary to determine the incidence of CO 2 auxotrophs of S. aureus, the factors that select these strains in the host, and the genetic basis of this type of auxotrophy.

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Section: Discussionmentioning

confidence: 99%

“…In general, the characteristics of SCVs facilitate persistence and recurrence of infections (7,13,14,24). Moreover, clinical cases of endocarditis, bacteremic pneumonia, and abscesses due to strains of CO 2 -dependent staphylococcus producing dwarf colonies have rarely been described in the medical literature (16,(19)(20)(21).…”

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confidence: 99%

Clinical and Molecular Characteristics of Infections with CO ₂ -Dependent Small-Colony Variants of Staphylococcus aureus

et al. 2010

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“…However, so far, there have been no attempts to characterize the metabolic changes or the underlying mechanism of CO 2 dependence in more detail. It is interesting that for this kind of SCVs, an irregular cell wall layer and tri-and tetraploid cells, along with many dividing forms, were also described (172).…”

Section: Co 2 -Dependent Scvsmentioning

confidence: 99%

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

2016

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SUMMARYSmall colony variants (SCVs) were first described more than 100 years ago forStaphylococcus aureusand various coagulase-negative staphylococci. Two decades ago, an association between chronic staphylococcal infections and the presence of SCVs was observed. Since then, many clinical studies and observations have been published which tie recurrent, persistent staphylococcal infections, including device-associated infections, bone and tissue infections, and airway infections of cystic fibrosis patients, to this special phenotype. By their intracellular lifestyle, SCVs exhibit so-called phenotypic (or functional) resistance beyond the classical resistance mechanisms, and they can often be retrieved from therapy-refractory courses of infection. In this review, the various clinical infections where SCVs can be expected and isolated, diagnostic procedures for optimized species confirmation, and the pathogenesis of SCVs, including defined underlying molecular mechanisms and the phenotype switch phenomenon, are presented. Moreover, relevant animal models and suggested treatment regimens, as well as the requirements for future research areas, are highlighted.

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“…However, for clinically derived SCVs, only mutations of the hemG, menB, menC, menE, menF , and thyA genes were identified. Besides these intensively studied mechanisms of SCV formation, less is known on SCVs dependent on unsaturated fatty acids or other compounds ( Sherris, 1952 ; Slifkin et al, 1971 ; Kaplan and Dye, 1976 ; Gómez-González et al, 2010 ; Lin et al, 2016 ). Hitherto, the fatty acid metabolism-linked genes accC, accD, fabF, fabI (eventually combined with fabD ), and plsX have been associated with the phenotype switch of fatty acid-auxotrophic SCVs, with fabF mutation being the only one found in a clinical isolate ( Parsons et al, 2011 , 2013 , 2014 ; Lin et al, 2016 ; Bazaid et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

The Energy-Coupling Factor Transporter Module EcfAA’T, a Novel Candidate for the Genetic Basis of Fatty Acid-Auxotrophic Small-Colony Variants of Staphylococcus aureus

et al. 2018

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Staphylococcal small-colony variants (SCVs) are invasive and persistent due to their ability to thrive intracellularly and to evade the host immune response. Thus, the course of infections due to this phenotype is often chronic, relapsing, and therapy-refractory. In order to improve treatment of patients suffering from SCV-associated infections, it is of major interest to understand triggers for the development of this phenotype, in particular for strains naturally occurring in clinical settings. Within this study, we comprehensively characterized two different Staphylococcus aureus triplets each consisting of isogenic strains comprising (i) clinically derived SCV phenotypes with auxotrophy for unsaturated fatty acids, (ii) the corresponding wild-types (WTs), and (iii) spontaneous in vitro revertants displaying the normal phenotype (REVs). Comparison of whole genomes revealed that clinical SCV isolates were closely related to their corresponding WTs and REVs showing only seven to eight alterations per genome triplet. However, both SCVs carried a mutation within the energy-coupling factor (ECF) transporter-encoding ecf module (EcfAA’T) resulting in truncated genes. In both cases, these mutations were shown to be naturally restored in the respective REVs. Since ECF transporters are supposed to be essential for optimal bacterial growth, their dysfunction might constitute another mechanism for the formation of naturally occurring SCVs. Another three triplets analyzed revealed neither mutations in the EcfAA’T nor in other FASII-related genes underlining the high diversity of mechanisms leading to the fatty acid-dependent phenotype. This is the first report on the ECF transporter as genetic basis of fatty acid–auxotrophic staphylococcal SCVs.

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Characterization of CO₂Dependent Microcolony Variants ofStaphylococcus aureus

Cited by 19 publications

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Clinical and Molecular Characteristics of Infections with CO ₂ -Dependent Small-Colony Variants of Staphylococcus aureus

Clinical and Molecular Characteristics of Infections with CO ₂ -Dependent Small-Colony Variants of Staphylococcus aureus

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

The Energy-Coupling Factor Transporter Module EcfAA’T, a Novel Candidate for the Genetic Basis of Fatty Acid-Auxotrophic Small-Colony Variants of Staphylococcus aureus

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Characterization of CO2Dependent Microcolony Variants ofStaphylococcus aureus

Cited by 19 publications

References 0 publications

Clinical and Molecular Characteristics of Infections with CO 2 -Dependent Small-Colony Variants of Staphylococcus aureus

Clinical and Molecular Characteristics of Infections with CO 2 -Dependent Small-Colony Variants of Staphylococcus aureus

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

The Energy-Coupling Factor Transporter Module EcfAA’T, a Novel Candidate for the Genetic Basis of Fatty Acid-Auxotrophic Small-Colony Variants of Staphylococcus aureus

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Characterization of CO₂Dependent Microcolony Variants ofStaphylococcus aureus

Clinical and Molecular Characteristics of Infections with CO ₂ -Dependent Small-Colony Variants of Staphylococcus aureus

Clinical and Molecular Characteristics of Infections with CO ₂ -Dependent Small-Colony Variants of Staphylococcus aureus