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Phenotypic and Genotypic Characteristics of Small Colony Variants and Their Role in Chronic Infection.

Johns BE, Purdy KJ, Tucker NP, Maddocks SE - Microbiol Insights (2015)

Bottom Line: They display unique phenotypic characteristics conferred in part by heritable genetic changes.Characteristically slow growing, SCVs comprise a minor proportion of the population from which they arise but persist by virtue of their inherent resilience and host adaptability.This review discusses some of the phenotypic and genotypic changes that enable SCVs to successfully proliferate within the host environment as potential pathogens and strategies that could ameliorate the resolution of infection where SCVs are present.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Science, Cardiff School of Health Sciences, Cardiff Metropolitan University, Cardiff, UK.

ABSTRACT
Small colony variant (SCV) bacteria arise spontaneously within apparently homogeneous microbial populations, largely in response to environmental stresses, such as antimicrobial treatment. They display unique phenotypic characteristics conferred in part by heritable genetic changes. Characteristically slow growing, SCVs comprise a minor proportion of the population from which they arise but persist by virtue of their inherent resilience and host adaptability. Consequently, SCVs are problematic in chronic infection, where antimicrobial treatment is administered during the acute phase of infection but fails to eradicate SCVs, which remain within the host causing recurrent or chronic infection. This review discusses some of the phenotypic and genotypic changes that enable SCVs to successfully proliferate within the host environment as potential pathogens and strategies that could ameliorate the resolution of infection where SCVs are present.

No MeSH data available.


Related in: MedlinePlus

Pure populations of bacteria often comprise WT (major population; blue) and SCV (minor population; orange), which arise spontaneously; under environmental stress, such as antibiotic treatment, the WT population is diminished and SCVs survive; under sustained stress, such as a course of antibiotics to treat an infection, the SCVs become the dominant members of the population. When the selective pressure is removed, WT organisms proliferate and become the dominant members of the population compared to slow-growing SCVs; significantly a proportion of SCVs revert to either the WT phenotype or a WT-like phenotype (green), which regains characteristics that enable faster growth.
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f2-mbi-8-2015-015: Pure populations of bacteria often comprise WT (major population; blue) and SCV (minor population; orange), which arise spontaneously; under environmental stress, such as antibiotic treatment, the WT population is diminished and SCVs survive; under sustained stress, such as a course of antibiotics to treat an infection, the SCVs become the dominant members of the population. When the selective pressure is removed, WT organisms proliferate and become the dominant members of the population compared to slow-growing SCVs; significantly a proportion of SCVs revert to either the WT phenotype or a WT-like phenotype (green), which regains characteristics that enable faster growth.

Mentions: Variants occur at random within microbial populations; most are transitory with only those changes that allow bacteria to remain viable and confer an advantage becoming fixed within a population. Microbial adaptation to a particular environment and competition between the members of a heterogeneous population, comprising a parent (wild type) and progeny (including mutants), are dictated by growth parameters and stresses.69 Numerous laboratory studies have demonstrated that successful microorganisms, namely, those that succeed within a given environment, do so because they exhibit the highest growth rate under prevailing conditions.70 Despite this, SCVs persist within microbial communities, albeit as a minor constituent that is never entirely outcompeted by the parental strain. Given the tenacity of SCVs to survive under stress, it might be expected that they should eventually predominate. Certainly with regard to antimicrobial interventions,71 this is the case, as the more susceptible parent strain is eradicated leaving behind a population of SCVs that can undergo reversion, which results in a recurrence of infection (Fig. 2).72 SCVs that arise during human infection appear better adapted for survival and persistence within the host73 despite their impaired rate of growth and increased host dependency. Selection because of loss or redundancy of metabolic activity is not unusual and under certain growth conditions,74 such as the host environment, might confer a fitness advantage, if not in terms of growth, in terms of survival.75 Many host-adapted and therefore invariably host-dependent pathogens undergo reductive evolution;76 driven by the host habitat and their ability to utilize host metabolites, such organisms become slow growing and nutritionally fastidious, often adopting an intracellular lifestyle.77 This process is ordinarily mediated by the loss of large fragments of genomic DNA. SCVs appear similar to host-adapted pathogens, and the loss of metabolic function renders them reliant on the host to meet their nutritional needs;78 indeed, many SCVs survive intracellularly. Where reductive evolution occurs in pathogens, it is correlated with increased virulence79 that is not observed for SCVs, which conversely seem to exhibit attenuated virulence.80 Significantly, pathogens that undergo reductive evolution do not regain “lost” genetic function81 unlike SCVs that are able to revert to WT or WT like once selective pressures, such as antimicrobial treatment, are removed (Figs. 1 and 2). Therefore, for SCVs, there is apparently a trade-off between virulence and persistence that exploits the ability to revert to a WT or WT-like variant, which is less host dependent and regains virulence. The specific adaptations that the minority SCV population depends on to ensure survival among their faster growing counterparts include the increased expression of surface adhesins as previously described. If two microorganisms are competing for the same human receptor, then those with a binding advantage (ie, more surface adhesins) are more likely to adhere.82,83 Combined with enhanced biofilm formation, such colonizers are less likely to be removed from the host by detachment.84 Intracellular survival provides more than simple protection from immunity, with the cell cytoplasm providing a nutritionally rich habitat for auxotrophic SCVs that is not afforded to the parental strain, but at the same time reduces competition for space at the tissue surface.85 It is proposed that in this way, both SCV and progenitor can coexist.


Phenotypic and Genotypic Characteristics of Small Colony Variants and Their Role in Chronic Infection.

Johns BE, Purdy KJ, Tucker NP, Maddocks SE - Microbiol Insights (2015)

Pure populations of bacteria often comprise WT (major population; blue) and SCV (minor population; orange), which arise spontaneously; under environmental stress, such as antibiotic treatment, the WT population is diminished and SCVs survive; under sustained stress, such as a course of antibiotics to treat an infection, the SCVs become the dominant members of the population. When the selective pressure is removed, WT organisms proliferate and become the dominant members of the population compared to slow-growing SCVs; significantly a proportion of SCVs revert to either the WT phenotype or a WT-like phenotype (green), which regains characteristics that enable faster growth.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4581789&req=5

f2-mbi-8-2015-015: Pure populations of bacteria often comprise WT (major population; blue) and SCV (minor population; orange), which arise spontaneously; under environmental stress, such as antibiotic treatment, the WT population is diminished and SCVs survive; under sustained stress, such as a course of antibiotics to treat an infection, the SCVs become the dominant members of the population. When the selective pressure is removed, WT organisms proliferate and become the dominant members of the population compared to slow-growing SCVs; significantly a proportion of SCVs revert to either the WT phenotype or a WT-like phenotype (green), which regains characteristics that enable faster growth.
Mentions: Variants occur at random within microbial populations; most are transitory with only those changes that allow bacteria to remain viable and confer an advantage becoming fixed within a population. Microbial adaptation to a particular environment and competition between the members of a heterogeneous population, comprising a parent (wild type) and progeny (including mutants), are dictated by growth parameters and stresses.69 Numerous laboratory studies have demonstrated that successful microorganisms, namely, those that succeed within a given environment, do so because they exhibit the highest growth rate under prevailing conditions.70 Despite this, SCVs persist within microbial communities, albeit as a minor constituent that is never entirely outcompeted by the parental strain. Given the tenacity of SCVs to survive under stress, it might be expected that they should eventually predominate. Certainly with regard to antimicrobial interventions,71 this is the case, as the more susceptible parent strain is eradicated leaving behind a population of SCVs that can undergo reversion, which results in a recurrence of infection (Fig. 2).72 SCVs that arise during human infection appear better adapted for survival and persistence within the host73 despite their impaired rate of growth and increased host dependency. Selection because of loss or redundancy of metabolic activity is not unusual and under certain growth conditions,74 such as the host environment, might confer a fitness advantage, if not in terms of growth, in terms of survival.75 Many host-adapted and therefore invariably host-dependent pathogens undergo reductive evolution;76 driven by the host habitat and their ability to utilize host metabolites, such organisms become slow growing and nutritionally fastidious, often adopting an intracellular lifestyle.77 This process is ordinarily mediated by the loss of large fragments of genomic DNA. SCVs appear similar to host-adapted pathogens, and the loss of metabolic function renders them reliant on the host to meet their nutritional needs;78 indeed, many SCVs survive intracellularly. Where reductive evolution occurs in pathogens, it is correlated with increased virulence79 that is not observed for SCVs, which conversely seem to exhibit attenuated virulence.80 Significantly, pathogens that undergo reductive evolution do not regain “lost” genetic function81 unlike SCVs that are able to revert to WT or WT like once selective pressures, such as antimicrobial treatment, are removed (Figs. 1 and 2). Therefore, for SCVs, there is apparently a trade-off between virulence and persistence that exploits the ability to revert to a WT or WT-like variant, which is less host dependent and regains virulence. The specific adaptations that the minority SCV population depends on to ensure survival among their faster growing counterparts include the increased expression of surface adhesins as previously described. If two microorganisms are competing for the same human receptor, then those with a binding advantage (ie, more surface adhesins) are more likely to adhere.82,83 Combined with enhanced biofilm formation, such colonizers are less likely to be removed from the host by detachment.84 Intracellular survival provides more than simple protection from immunity, with the cell cytoplasm providing a nutritionally rich habitat for auxotrophic SCVs that is not afforded to the parental strain, but at the same time reduces competition for space at the tissue surface.85 It is proposed that in this way, both SCV and progenitor can coexist.

Bottom Line: They display unique phenotypic characteristics conferred in part by heritable genetic changes.Characteristically slow growing, SCVs comprise a minor proportion of the population from which they arise but persist by virtue of their inherent resilience and host adaptability.This review discusses some of the phenotypic and genotypic changes that enable SCVs to successfully proliferate within the host environment as potential pathogens and strategies that could ameliorate the resolution of infection where SCVs are present.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Science, Cardiff School of Health Sciences, Cardiff Metropolitan University, Cardiff, UK.

ABSTRACT
Small colony variant (SCV) bacteria arise spontaneously within apparently homogeneous microbial populations, largely in response to environmental stresses, such as antimicrobial treatment. They display unique phenotypic characteristics conferred in part by heritable genetic changes. Characteristically slow growing, SCVs comprise a minor proportion of the population from which they arise but persist by virtue of their inherent resilience and host adaptability. Consequently, SCVs are problematic in chronic infection, where antimicrobial treatment is administered during the acute phase of infection but fails to eradicate SCVs, which remain within the host causing recurrent or chronic infection. This review discusses some of the phenotypic and genotypic changes that enable SCVs to successfully proliferate within the host environment as potential pathogens and strategies that could ameliorate the resolution of infection where SCVs are present.

No MeSH data available.


Related in: MedlinePlus