Small Colony Variants of Staphylococcus aureus in Persistent Infections

Small colony variants (SCVs) of Staphylococcus aureus are phenotypic subpopulations characterised by slow growth, reduced colony size on agar and profound metabolic alterations. These variants display diminished expression of key virulence factors yet exhibit enhanced capacity for intracellular survival, biofilm formation and tolerance to antibiotics. SCVs arise through diverse mechanisms, including defects in electron transport or thymidylate synthesis, activation of the stringent response and reversible chromosomal rearrangements. Global regulators such as the alternative sigma factor SigB and the Agr quorum-sensing system govern the transition between wild-type and SCV phenotypes, balancing acute virulence and long-term persistence. Clinically, SCVs are implicated in chronic and relapsing infections ranging from cystic fibrosis airways to prosthetic-device and implantable electronic device infections, often evading immune clearance and standard antibiotic regimens. Understanding SCV biology has driven the development of diagnostic strategies to detect metabolically altered cells and inspired therapeutic approaches targeting persistence pathways, such as inhibition of SigB activity or modulation of the Agr system, in order to overcome recalcitrant staphylococcal infections and reduce relapse.

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Small Colony Variants of Staphylococcus aureus in Persistent Infections publication trend

The graph below shows the total number of articles in small colony variants of staphylococcus aureus in persistent infections across all publications each year (not limited to Nature Index journals).

Technical terms

Small colony variant (SCV): A slow-growing form of S. aureus with small colonies on solid media, altered metabolism and enhanced intracellular persistence, linked to chronic infections.

Auxotrophism: A genetic requirement for external metabolic substrates (such as haem, menadione or thymidine) due to mutations impairing biosynthetic pathways.

Biofilm: A structured community of bacteria encased in an extracellular matrix adherent to surfaces, which increases resistance to antibiotics and immune clearance.

Quorum sensing: A bacterial cell-to-cell communication system, exemplified by the Agr circuit in S. aureus, that uses autoinducer peptides to synchronise gene expression including virulence determinants.

Stringent response: A global stress adaptation mediated by accumulation of guanosine pentaphosphate/tetraphosphate (ppGpp), leading to downregulation of growth and promotion of persistence phenotypes.

Sigma factor SigB: An alternative transcriptional regulator in S. aureus that activates stress response genes and facilitates the switch to the SCV phenotype during chronic infection.

References

1. Reduced Glycolysis and Cytotoxicity in Staphylococcus aureus Isolates from Chronic Rhinosinusitis as Strategies for Host Adaptation. International Journal of Molecular Sciences (2024).
2. Unravelling staphylococcal small-colony variants in cardiac implantable electronic device infections: clinical characteristics, management, and genomic insights. Frontiers in Cellular and Infection Microbiology (2024).
3. Persistence of Staphylococcus aureus: Multiple Metabolic Pathways Impact the Expression of Virulence Factors in Small-Colony Variants (SCVs). Frontiers in Microbiology (2020).
4. Biofilm and Small Colony Variants—An Update on Staphylococcus aureus Strategies toward Drug Resistance. International Journal of Molecular Sciences (2022).
5. Staphylococcus aureus Small Colony Variants (SCVs): a road map for the metabolic pathways involved in persistent infections. Frontiers in Cellular and Infection Microbiology (2014).
6. Sigma Factor SigB Is Crucial to Mediate Staphylococcus aureus Adaptation during Chronic Infections. PLOS Pathogens (2015).
7. Two Novel Point Mutations in Clinical Staphylococcus aureus Reduce Linezolid Susceptibility and Switch on the Stringent Response to Promote Persistent Infection. PLOS Pathogens (2010).
8. Unstable chromosome rearrangements in Staphylococcus aureus cause phenotype switching associated with persistent infections. Proceedings of the National Academy of Sciences of the United States of America (2019).