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  Table of Contents  
Year : 2015  |  Volume : 33  |  Issue : 2  |  Page : 296-297

Small colony variants of Staphylococcus aureus: A clinical and laboratory challenge

Department of Microbiology and Parasitology, Faculty of Veterinary Medicine, University of Tripoli, Tripoli, Libya

Date of Submission05-Dec-2014
Date of Acceptance31-Dec-2014
Date of Web Publication10-Apr-2015

Correspondence Address:
M O Ahmed
Department of Microbiology and Parasitology, Faculty of Veterinary Medicine, University of Tripoli, Tripoli
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.154886

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How to cite this article:
Ahmed M O. Small colony variants of Staphylococcus aureus: A clinical and laboratory challenge. Indian J Med Microbiol 2015;33:296-7

How to cite this URL:
Ahmed M O. Small colony variants of Staphylococcus aureus: A clinical and laboratory challenge. Indian J Med Microbiol [serial online] 2015 [cited 2019 Dec 6];33:296-7. Available from:

Dear Editor,

Staphylococcus aureus is a widespread bacterial pathogen, responsible for clinical complications ranging from skin infections to life-threatening illnesses. Certain strains of bacterial organisms, particularly S. aureus, are capable of producing slow growing sub-populations, designated as small colony variants (SCVs), which are frequently isolated in hospital settings. [1],[2] These can persistently colonize humans and are associated with antibiotic exposure. [2] Laboratory studies have revealed phenotypic and biochemical characteristics of SCVs distinctive from the wild-type strains, including altered colony morphology, biochemical reactivity and expression of virulence factors, as well as decreased antibiotic susceptibility. [3] Yet these insights have not translated to an effective clinical method to reduce S. aureus SCV infections.

Persistence and Intracellularity of S. aureus SCVs

Persistence of SCV infections, regardless of species and despite species-targeted therapy, represents a serious clinical complication. [3],[4] Staphylococcal persisters have been largely reported, yet the underlying mechanisms of this pathogenic state remain to be fully elucidated. Compared to S. aureus, the derivative SCVs can survive intracellularly for a longer period of time without manifesting a recognizable symptomology. This asymptomatic persistence has been partially attributed to a weaker immune-stimulating effect related to the lower expression and activation of virulence genes. [3]

A key regulator of the formation and persistence of S. aureus SCVs is the accessory virulence regulatory gene (agr), and the intracellular effector of the quorum-sensing system (RNAIII). [2] decreased agr and RNAIII expression contributes to the lower virulence of S. aureus SCVs, consequently facilitating chronic infection. Another SCV-related mechanism involves the S. aureus sigma factor B (SigB) that regulates expression of virulence genes and stress-response proteins. [2]

S. aureus nosocomial infections frequently present as coinfections with other nosocomial bacteria. The observation of Pseudomonas aeruginosa being commonly isolated with S. aureus SCVs from clinical specimens [5] led to studies of synergistic interactions between the two species.[5] However, the in vivo nosocomial condition is not so straight-forward, as S. aureus SCVs can revert to normal type, [2],[4] possibly due to other inter-species interactions involving the quorum-sensing mechanism and biofilm formation.

A Challenge for Laboratories and Bacteriologists

The atypical phenotypic and biochemical characteristics of S. aureus SCVs hinder their detection and analysis in the laboratories. [1],[3],[5] The colonial appearance of S. aureus SCVs can be misinterpreted as corynebacteria or non-haemolytic streptococci for instance. Despite having a remarkably slower growth rate (1/10 of typical growing colony), culturing for extended and inattentive periods of time or on selective medium can lead to misidentification as normal S. aureus. [2],[5] The slow growing feature of S. aureus SCVs also complicates analysis by antimicrobial susceptibility tests, which require accurate calibration and standardization. These complications arise from the sub-optimal reliability of common protocols for antimicrobial susceptibility testing, including disc diffusion, E-test and automated systems; however, application of a reference guideline can improve the accuracy of detection, [5] suggesting a possible reliable approach for antimicrobial testing of S. aureus SCVs.

The need for accurate detection methods extends beyond laboratory investigations, and is critical for clinical diagnosis. In this regard, molecular techniques, such as gene screening, are the most promising. Sequencing-based methods can also help to identify various gentoypes and phenotypes of S. aureus SCVs; for example, the 16S ribosomal deoxyribonucleic acid (rDNA) sequencing can identify coagulase-negative staphylococcal SCVs, and the mec and nuc gene sequences can identify SCVs derived from MRSAs.

The overall strategies to curb the impending obsolesce of our limited array of antimicrobial drugs must include SVCs, creating new techniques to effectively detect and manipulate these agents in the laboratory setting and to control their infection rate in the hospital setting.

 ~ References Top

Bhattacharyya S, Kumar D. Small colony variants of Staphylococcus aureus: Enemies with hidden weapons. Indian J Med Microbiol 2014;32:460-1.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
Proctor RA, von EC, Kahl BC, Becker K, McNamara P, Herrmann M, et al. Small colony variants: A pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 2006;4:295-305.  Back to cited text no. 2
Sendi P, Proctor RA. Staphylococcus aureus as an intracellular pathogen: The role of small colony variants. Trends Microbiol 2009;17:54-8.  Back to cited text no. 3
Tuchscherr L, Heitmann V, Hussain M, Viemann D, Roth J, von EC, et al. Staphylococcus aureus small-colony variants are adapted phenotypes for intracellular persistence. J Infect Dis 2010 1;202:1031-40.  Back to cited text no. 4
Yagci S, Hascelik G, Dogru D, Ozcelik U, Sener B. Prevalence and genetic diversity of Staphylococcus aureus small-colony variants in cystic fibrosis patients. Clin Microbiol Infect 2013;19:77-84.  Back to cited text no. 5


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