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Year : 2016  |  Volume : 9  |  Issue : 2  |  Page : 137-139
Small colony variants and their clinical significance

Department of Microbiology, Prathima Institute of Medical Sciences, Karimnagar, Telangana, India

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Date of Web Publication24-Feb-2016


Among the many factors that contribute to bacterial colonization, persistence and development of infection, the ability of microorganisms to form small colony variants (SCVs) assumes great significance. Although bacteria require intrinsic virulence factors to cause pathogenesis, some of them regularly evolve mechanisms to evade immune mechanisms, become resistant to antibiotics, and sustain in the human/animal cells to cause chronic infections. This mini review highlights the recent advances in the study of SCVs.

Keywords: Antibiotic resistance, bacterial virulence/virulence, small colony variants (SCVs)

How to cite this article:
Venkataramana V. Small colony variants and their clinical significance. Ann Trop Med Public Health 2016;9:137-9

How to cite this URL:
Venkataramana V. Small colony variants and their clinical significance. Ann Trop Med Public Health [serial online] 2016 [cited 2021 Jan 24];9:137-9. Available from:

   Introduction Top

Bacterial subpopulation resulting from genetic mutations that develop additional physiologic characteristics that allow them to survive in the host tissue and evade defence mechanism and the antibiotic exposure are termed as small colony variants (SCVs). [1] The exact mechanism of genetic change has not been well-explained but mutation at thymidylate synthase gene (thyA) was found associated with the evolution of SCVs. SCVs show growth deficiency and form small colonies in laboratory isolations. It has been noted that chronic antibiotic exposure, starvation, and the effect of host cationic antimicrobial peptides (lactoferrin) could result in the emergence of SCVs. Colony morphology of such bacteria is unique showing minute/pinpoint colonies that measure not more than 1 mm in diameter and show no pigmentation [Figure 1]. In contrast to the wild strain, the SCVs not only differ in the colony characters but also show increased generation time and react to biochemical reactions differently (usually inert). The most common conditions that could predispose a person to infection with SCVs include organ functional abnormalities (autoimmune skin diseases, cystic fibrosis), infections related to foreign body implants, and osteomyelitis. [2] SCVs attributed to their slow growth rates and hindered adenosine triphosphate (ATP) generation develop a mechanism that decreases the influx of the drug and contributes to antibiotic resistance. The antibiotics found ineffective against SCVs include sulfonamides, trimethoprim, gentamicin, and other aminoglycosides. [3]
Figure 1: Small colony variant of Pseudomonas aeruginosa showing very small and nonpigmented colonies

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   Recent Advances Top

A recent research report has confirmed that there are three characteristic attributes of SCVs including downregulation of metabolism, virulence determinants, and delayed growth and upregulation of genes (sigB) responsible for biofilm formation. [4] Previous research studies have also noted that bacteria intrinsically have the ability to undergo phenotypic twitching where in a quarter of bacterial clones among the initial colony has the ability to form SCVs which was also experimentally proved in animals. [5],[6]

Other recent studies have noted that bacteria have the ability to form SCVs in cases where the infection is not completely eliminated and the bacterial species persist inside the cells even after the completion of therapy resulting in chronic and recurrent infections. [7],[8]

Abnormalities in ribonucleic acid (RNA) metabolism and processing including altered mRNA levels have been associated with the formation of SCVs. [9]

   Discussion Top

Most of the studies on SCVs happened among Staphylococcus aureus and only scanty literature is available on SCVs of other bacteria including Pseudomonas aeruginosa.[3],[10] Epidemiology of SCVs has been sparsely reported in literature which is mostly presented as cases or isolated observations. [11],[12],[13] It is not clear whether all bacteria are capable of forming SCVs or this character is found exclusively in some bacteria as evidenced by the research studies reported thus far. There are some studies on SCVs of Staphylococcus aureus and hardly any in case of other microorganisms. [14] Long-term exposure to gentamicin-induced formation of SCVs among strains of  Escherichia More Details coli (E. coli), Pseudomonas aeruginosa and Staphylococcus epidermidis (S. epidermidis), chloramphenicol and ciprofloxacin-induced SCV formations in E. coli, and tetracycline-stimulated SCV formation among S. epidermidis was also reported in literature. [15] SCVs from these bacterial species were found to share common characters related to SCV phenotype that included abnormal growth and biochemical characteristics, auxotrophy for compounds involved in electron transport, reduction in the expression of virulence factors, and reduced antimicrobial susceptibility. Additionally, all SCVs showed an increased capacity to form biofilms.

In the era of antimicrobial resistance, patient care and management assumes significance and is complex. Isolation of bacteria from clinical specimens and identification of physiological, biochemical, and molecular mechanisms engineered by microorganisms to evade immunological defence (biofilm formation) and antimicrobial resistance could be instrumental in better patient care. Clinical microbiology laboratories should device and implement diagnostic strategies to identify the microorganisms showing morphological, physiological, biochemical, and genetic variations.

   Conclusion Top

SCVs are the microbial clones evolved by selection to counter unfavourable growth environments to sustain immunological defence, antibiotic effect, and to continue colonization and result in infection which is usually chronic, persistent, and antibiotic resistant. Microorganisms causing infections among debilitated individuals (cystic fibrosis), bacteria responsible for chronic and persistent infections, and microorganisms showing significant resistance towards antimicrobial agents could be armed with special abilities which need further extensive research.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Proctor RA, von Eiff C, 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 Microb Rev 2006;4:295-305.  Back to cited text no. 1
Carzino R, King L, Hart E, Ranganathan S. WS19.3 Prevalence of small colony variants of Staphylococcus aureus from lower respiratory tract specimens. J Cyst Fibros 2015;14:S35.  Back to cited text no. 2
Melter O, Radojeviè B. Small colony variants of Staphylococcus aureus - Review. Folia Microbiol (Praha) 2010;55:548-58.   Back to cited text no. 3
Kahl BC. Small colony variants (SCVs) of Staphylococcus aureus - A bacterial survival strategy. Infect Genet Evol 2014;21:515-22.   Back to cited text no. 4
Tuchscherr L, Medina E, Hussain M, Völker W, Heitmann V, Niemann S, et al. Staphylococcus aureus phenotype switching: An effective bacterial strategy to escape host immune response and establish a chronic infection. EMBO Mol Med 2011;3:129-41.   Back to cited text no. 5
Horst SA, Hoerr V, Beineke A, Kreis C, Tuchscherr L, Kalinka J, et al. A novel mouse model of Staphylococcus aureus chronic osteomyelitis that closely mimics the human infection: An integrated view of disease pathogenesis. Am J Pathol 2012;181:1206-14.   Back to cited text no. 6
Garcia LG, Lemaire S, Kahl BC, Becker K, Proctor RA, Denis O, et al. Antibiotic activity against small-colony variants of Staphylococcus aureus: Review of in vitro, animal and clinical data. J Antimicrob Chemother 2013;68:1455-65.  Back to cited text no. 7
Amato SM, Fazen CH, Henry TC, Mok WW, Orman MA, Sandvik EL, et al. The role of metabolism in bacterial persistence. Front Microbiol 2014;5:70.   Back to cited text no. 8
Proctor RA, Kriegeskorte A, Kahl BC, Becker K, Löffler B, Peters G. Staphylococcus aureus Small Colony Variants (SCVs): A road map for the metabolic pathways involved in persistent infections. Front Cell Infect Microbiol 2014;4:99.   Back to cited text no. 9
Sousa AM, Pereira MO. Pseudomonas aeruginosa diversification during infection development in cystic fibrosis lungs-A review. Pathogens 2014;3:680-703.   Back to cited text no. 10
Seifert H, von Eiff C, Fätkenheuer G. Fatal case due to methicillin-resistant Staphylococcus aureus small colony variants in an AIDS patient. Emerg Infect Dis 1999;5:450-3.  Back to cited text no. 11
Ahmed MO, Aghila ESh, Elramalli AK, Agdih MS. Staphylococcal small colony variants from a Libyan hospital. J Lab Physicians 2015;7:68-9.   Back to cited text no. 12
[PUBMED]  Medknow Journal  
Gitomer SA, Ramakrishnan VR, Malcolm KC, Kofonow JM, Ir D, Frank DN. Initial investigation of small colony variants of Staphylococcus aureus in chronic rhinosinusitis. Am J Rhinol Allergy 2015;29:29-34.  Back to cited text no. 13
Cervantes-García E, García-Gonzalez R, Reyes-Torres A, Resendiz-Albor AA, Salazar-Schettino PM. Staphylococcus aureus small colony variants in diabetic foot infections. Diabet Foot Ankle 2015;6:26431.  Back to cited text no. 14
Norville PJ. Small colony variants in Staphylococcus aureus and other species: Antibiotic selection, antimicrobial susceptibility, and biofilm formation. 2011. Available from: [Last accessed on 2015 Aug 27].  Back to cited text no. 15

Correspondence Address:
Venkataramana Venkataramana
Department of Microbiology, Prathima Institute of Medical Sciences, Karimnagar - 505 417, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.177406

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