A full genomic characterization of the development of a stable Small Colony Variant cell-type by a clinical Staphylococcus aureus strain

Bui, Long M.G.; Kidd, Stephen P.

doi:10.1016/j.meegid.2015.10.011

Cited by 35 publications

(28 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinically, the phenotypes of SCVs are associated with persistent and recurrent infections in S. aureus and P. aeruginosa due to their increased ability to persist in mammalian cells and increased antimicrobial resistance [ 2 ]. In S. aureus, Long et al have demonstrated that the minimum bacteriocidal concentration was two- to fourfold higher than the parental strain, which may correlate to the bacterial persister cells, however, there was very little change in MIC for SCVs [ 30 ]. Consistently, a slightly increase in MIC of IMI and GEN was observed in S. Typhimurium SCV mutants.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and genetic changes in the life cycle of small colony variants of Salmonella enterica serotype Typhimurium induced by streptomycin

et al. 2016

Ann Clin Microbiol Antimicrob

View full text Add to dashboard Cite

BackgroundSmall colony variants (SCVs), constituting a slow-growing subpopulation of bacteria that facilitates persistence in lethal environmental conditions, are able to revert to the phenotype of rapid growth for further proliferation and transmission. Salmonella enterica serotype Typhimurium is one of the most important foodborne pathogens. This study investigated the genetic mechanisms how SCVs induced by streptomycin reverted to the fast-growing phenotype and the phenotypic changes of SCVs among their complete life cycle in S.Typhimurium.MethodsSalmonella Typhimurium SCVs were obtained by streptomycin treatment and their revertants were collected in the absence of antibiotics. The fitness, antimicrobial susceptibility, biofilm formation, and the biofilm-related genes expression were analyzed in comparison to their wild type strain, and the whole genome sequencing was performed to identify the genetic changes in the life cycle of S. Typhimurium SCVs.ResultsSmall colony variants were characterized by an increased antimicrobial resistance to streptomycin (64-fold), imipenem (twofold), and gentamicin (fourfold). A significant increase in biofilm production with higher expression of csgB was observed in SCVs (P < 0.01). The genetic alterations of all SCVs occurred in ubiE gene (coenzyme Q8 and menaquinone synthesis) with frameshift mutations. However, all fast-growing revertants again lost the trait of increased biofilm production (P > 0.05), in which two modes of the genetic changes for reversing to the rapidly growing form were observed: four revertants harbored a secondary mutation in ubiE, which reinstated most of the amino acid sequence of the ubiE, and other four revertants harbored a mutation in prfB.ConclusionsSalmonella Typhimurium could switch to the phenotype of SCVs under the treatment of streptomycin by a mutation in ubiE, partially combined with increased production of biofilm, and these SCVs could escape from growth restriction by a compensatory mutation in prfB or a new mutation in ubiE. These findings may contribute to establishing phenotype-directed treatments against SCVs of S.Typhimurium.Electronic supplementary materialThe online version of this article (doi:10.1186/s12941-016-0151-3) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Phenotypic and genetic changes in the life cycle of small colony variants of Salmonella enterica serotype Typhimurium induced by streptomycin

et al. 2016

Ann Clin Microbiol Antimicrob

View full text Add to dashboard Cite

show abstract

“…However, by using whole-genome sequencing, Gao et al identified and confirmed a further mechanism for SCVs due to mutations in relA, with a permanent activation of the stringent stress response (148,149). Just recently, Bui et al studied a stable SCV induced by host-generated chemical stresses by full genomic characterization (150,151). These studies revealed a new type of stable SCVs, which are characterized by mutations in mgrA and rsbU (150).…”

Section: Pathogenesis Defined Underlying Mechanisms and Mutationsmentioning

confidence: 99%

“…Just recently, Bui et al studied a stable SCV induced by host-generated chemical stresses by full genomic characterization (150,151). These studies revealed a new type of stable SCVs, which are characterized by mutations in mgrA and rsbU (150).…”

Section: Pathogenesis Defined Underlying Mechanisms and Mutationsmentioning

confidence: 99%

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

2016

View full text Add to dashboard Cite

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.

show abstract

“…When exposed to stressful conditions, Bcc populations can undergo phenotypical and genetic adaptations that confer selective advantage. One example of such versatility is the formation of small colony variants (SCVs), which typically exhibit one-tenth the size of the colonies associated with the parent strain, and are characterized by a slow specific growth rate (Häussler et al, 1999 ; Proctor et al, 2006 ; Kahl, 2014 ; Bui and Kidd, 2015 ). Besides being considered a pathogenesis factor, formation of SCVs is also thought to contribute for the establishment of recurrent infections, leading to lung function deterioration and development of fatal systemic infections (Häussler et al, 2003 ; Proctor et al, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

Adaptation and Survival of Burkholderia cepacia and B. contaminans During Long-Term Incubation in Saline Solutions Containing Benzalkonium Chloride

Tavares

Kozak

Balola

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

The Burkholderia cepacia complex (Bcc) is a group of opportunistic pathogenic bacteria with a remarkable metabolic capacity and broad genotypic/phenotypic plasticity, allowing their adaptation to hostile conditions, including nutrient depleted solutions containing antimicrobial agents. Bcc bacteria are feared contaminants in pharmaceutical industries and cause nosocomial outbreaks, posing health threats to immunocompromised individuals and cystic fibrosis (CF) patients. In this study, the adaptation and survival of B. cepacia and B. contaminans isolates was investigated after long-term incubation in nutrient depleted saline solutions supplemented with increasing concentrations of the biocidal preservative benzalkonium chloride (BZK), recreating the storage conditions of pharmaceutical products. These epidemiologically related isolates were recovered from intrinsically contaminated saline solutions for nasal application and from two CF patients. Long-term incubation in saline solutions containing BZK led to the development of bacterial sub-populations that survived for at least 16 months, despite an initial 2–3 log decrease in viability, displaying a progressive dose-dependent decrease of colony and cell size, including the appearance of small colony variants (SCVs). Bacterial colonies lost pigmentation, changed the morphotype from rough to smooth and produced more spherical cells during extended incubation with BZK. The development of macroscopically visible cellular aggregates, rich in polysaccharide and harboring viable cells in their interior was triggered by BZK. The existence of a metabolic pathway for BZK degradation was confirmed through genome analysis. This study reveals mechanisms underlying the prevalence of Bcc bacteria as contaminants of pharmaceutical products containing BZK, which often lead to false-negative results during quality control and routine testing.

show abstract

A full genomic characterization of the development of a stable Small Colony Variant cell-type by a clinical Staphylococcus aureus strain

Cited by 35 publications

References 88 publications

Phenotypic and genetic changes in the life cycle of small colony variants of Salmonella enterica serotype Typhimurium induced by streptomycin

Phenotypic and genetic changes in the life cycle of small colony variants of Salmonella enterica serotype Typhimurium induced by streptomycin

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

Adaptation and Survival of Burkholderia cepacia and B. contaminans During Long-Term Incubation in Saline Solutions Containing Benzalkonium Chloride

Contact Info

Product

Resources

About