Staphylococcus capitis: Characteristics and Implications

Table of Contents

• Introduction
• Classification
• Habitat
• Morphology
• Cultural Characteristics
• Biochemical Characteristics
• Virulence factors
• Pathogenesis
• Clinical Manifestations
• Lab Diagnosis
• Treatment
• Prevention

Introduction

• Staphylococcus capitis is a Gram-positive, coagulase-negative coccus, present as a part of the human normal flora mostly localized in areas around the scalp and face that have been lately associated with bacteria in neonates.
• Staphylococcus capitis is a coagulase-negative Staphylococci with documented potential for both human disease and nosocomial spread.
• It is non-motile, non-spore-forming facultatively anaerobic even though the best growth is observed under aerobic conditions.
• The species name ‘capitis’ is derived from the Latin name ‘caput’ meaning head, indicating the part of the human body where cutaneous populations of this species are usually the largest and most frequent.
• S. capitis is further divided into two subspecies on the basis of various characteristics; S. capitis subsp. capitis and S. capitis subsp. ureolyticus.
• It was first discovered or isolated by Kloos and Schleifer in 1975 from human skin; subspecies S. capitis subsp. capitis was also identified by Kloos and Schleifer in 1975 but subspecies S. capitis subsp. ureolyticus was discovered by Bannerman and Kloos in 1991.
• Staphylococcus capitis has been implicated in biofilm-related infections such as endocarditis, urinary tract infection, and catheter-related bacteremia. S. capitis is likely to be transmitted mostly via humans.
• S. capitis is particularly important in neonatal intensive care units where it causes up to 20% of cases of neonatal sepsis.
• Both S. capitis subsp. capitis and S. capitis subsp. ureolyticus are present on the human body as a part of the normal flora, mostly around the head.

Classification

• Staphylococcal species are classified based on criteria such as cell wall composition, G + C content of DNA, DNA–DNA hybridization, 16S rRNA sequence similarities, and genome sizes.
• Members of the same species typically exhibit DNA-binding values of 70 percent or higher, while organisms from distinct species display relative DNA-binding values below 70 percent.
• The subspecies classification of S. capitis involves assessing urease activity, the ability to produce acid from maltose in anaerobic conditions, fatty acid profile, colony size, and DNA sequence variations.

The taxonomical classification of S. capitis is determined by these factors.

Domain	Bacteria
Phylum	Firmicutes
Class	Bacilli
Order	Bacillales
Family	Staphylococcaceae
Genus	Staphylococcus
Species	S. capitis
Subspecies	S. capitis subsp. capitis
Subspecies	S. capitis subsp. ureolyticus

Habitat

• S. capitis subsp. capitis primarily thrives on the heads of humans, while S. capitis subsp. ureolyticus predominantly resides in the heads of primates.
• Although preadolescent children typically harbor other coagulase-negative Staphylococci on their scalps, S. capitis takes over after puberty.
• The surge in S. capitis populations on the scalp during puberty is linked to increased sebaceous gland activity.
• S. capitis subsp. capitis strongly favors the human head, while S. capitis subsp. ureolyticus moderately prefers it.
• Furthermore, S. capitis subsp. ureolyticus can be found in the external auditory meatus of adults, but it lacks urease activity due to minimal urea presence.
• Despite their affinity for the head, S. capitis is occasionally detected in other body areas such as arms and legs.

Morphology

• S. capitis subsp. capitis presents as non-motile, Gram-positive cocci, lacking spore-forming ability, and exhibiting an average diameter of 0.8–1.2 μm.
• Cell arrangements typically occur in pairs, forming tetrads in irregular grapelike clusters due to division in multiple planes.
• These cells are facultatively anaerobic, and encapsulation levels vary among S. capitis strains.
• The cell wall composition includes peptidoglycan and teichoic acid, constituting approximately 60–30 percent, respectively, of the dry weight.
• Peptidoglycan, the primary structural polymer in the wall, plays a crucial role in maintaining the cell's spherical shape.
• The cell membrane, a lipid-protein bilayer, consists of phospholipids, glycolipids, menaquinones, and carotenoids. Associated proteins include adenosine triphosphatase, polyprenolphosphokinase, various oxidases and dehydrogenases, and several penicillin-binding proteins.
• While some cell wall-associated proteins in S. capitis have been identified, such as SdrF, SdrG, and SdrH from the Sdr protein family, their characterization reveals roles in promoting adherence to extracellular matrix proteins and soluble plasma components, facilitating attachment to host surfaces.

Cultural Characteristics 

Staphylococcus species can be cultivated on various agar and liquid media, facilitating identification and selective growth. They thrive in diverse culture media such as nutrient agar, Mannitol Salt Agar, P agar, and thioglycollate medium. Species-level identification can be achieved based on distinctive cultural characteristics, including growth patterns and colony morphology.

Colony morphology of S. capitis on different media:

1. Nutrient Agar (NA):

Circular colonies of S. capitis, ranging from cream-colored to white, with a diameter of around 1 mm and an entire margin. The colonies exhibit raised elevation, a dense center, and transparent borders.

2. Mannitol Salt Agar (MSA):

Yellow colonies, approximately 1-3 mm in size, surrounded by yellow zones indicative of acid release from mannitol utilization.

3. P Agar:

S. capitis subsp. capitis: White or greyish colonies, 1-3 mm in diameter, appear smooth, slightly convex, glistening, and opaque on P agar. Color may change to yellow or yellow-orange after storage at 1-4°C.

S. capitis subsp. ureolyticus: Raised, opaque, glistening colonies with potential yellow pigmentation after late incubation. Colonies may be smooth or rough, featuring slightly irregular or entire edges, with a diameter of about 4.3–7.1 mm.

4. Blood Agar (BA):

Wrinkled, medium-sized (1-4 mm) β-hemolytic colonies with an opaque, rough white appearance are observed. Colony pleiomorphism is common on blood agar, and prominent hemolysis is visible after 48 hours of incubation.

S. capitis subsp. ureolyticus: No hemolysis is observed.

Biochemical Characteristics

The biochemical characteristics of S. capitis can be tabulated as follows:

S.N	Biochemical Characteristics	Staphylococcus capitis
1.	Capsule	No capsule
2.	Shape	Cocci
3.	Catalase	Positive (+)
4.	Oxidase	Negative (-)
5.	Citrate	Negative (-)
6.	Methyl Red (MR)	Negative (-)
7.	Voges Proskauer (VP)	Negative (-)
8.	Urease	Negative (-)
9.	Coagulase	Negative (-)
10.	DNase	Positive (+)
11.	Clumping factor	Negative (-)
12.	Gas	Positive (+)
11.	H2S	Positive (+)
12.	Hemolysis	Positive (+) for S. capitis subsp. capitis and Negative (-) for S. capitis subsp. ureolyticus.
13.	Motility	Negative (-)
14.	Nitrate Reduction	Positive (+) for S. capitis subsp. capitis, variable for S. capitis subsp. ureolyticus.
15.	Gelatin Hydrolysis	Negative (-)
16.	Pigment Production	Variable
17.	Novobiocin resistance	Susceptible
18.	Lysozyme resistance	Resistant
19.	Bile esculin test	Negative (-)
20.	Growth on 1.5% NaCl	Variable

Fermentation

S.N	Substrate	Staphylococcus capitis
1.	Mannitol	Positive (+)
2.	Glucose	Positive (+) May produce only d-lactate or both l- and d-lactate from glucose anaerobically.
3.	Fructose	Positive (+)
4.	Galactose	Negative (-)
5.	Lactose	Variable
6.	Maltose	Negative (-) for S capitis subsp. capitis and Positive (+) for S. capitis subsp. ureolyticus.
7.	Mannose	Positive (+)
8.	Raffinose	Negative (-)
9.	Ribose	Negative (-)
10.	Sucrose	Positive (+)
11.	Starch	Negative (-)
12.	Trehalose	Negative (-)
13.	Xylose	Negative (-)
14.	Salicin	Negative (-)
15.	Glycerol	Positive (+)
16.	Dulcitol	Negative (-)
17.	Cellobiose	Negative (-)
18.	Rhamnose	Negative (-)
19.	Arabinose	Negative (-)
20.	Inulin	Negative (-)
21.	Sorbitol	Negative (-)
22.	Pyruvate	Negative (-)

Enzymatic Reactions

S.N	Enzymes	Staphylococcus capitis
1.	Hyaluronidase	Variable
2.	Acetoin	Variable
3.	Alkaline Phosphatase	Variable
4.	Ornithine Decarboxylase	Negative (-)
5.	Pyrrolidonyl aminopeptidase	Positive (+)
6.	β-galactosidase	Negative (-)

Distinguishing S. capitis subsp. ureolyticus from S. capitis subsp. capitis involves assessing urease production, the capability to generate acid from maltose, and variations in fatty acid composition.

Virulence factors

While coagulase-negative Staphylococci generally exhibit lower virulence compared to more potent species like Staphylococcus aureus, Staphylococcus capitis does possess several encoded factors crucial for biofilm production, persistence, and evading the immune system. Additionally, S. capitis is associated with an endopeptidase acting as a bacteriocin. These virulence factors primarily function in shielding the organism against host immune responses and building resistance to various antimicrobial agents.

1. Biofilm Formation:

• Biofilm, a complex structure of bacterial cells and extracellular matrix, acts as a barrier against immune cells.
• The process is regulated by specific genes encoding proteins facilitating bacterial binding to surfaces and each other.
• S. capitis employs poly-N-acetylglucosamine (PNAG) production, dependent on the ica locus identified in its genome, for intercellular adhesion.
• The plasmin-sensitive protein Pls promotes cell-cell interaction, resembling the accumulation-associated protein (Aap) in S. epidermidis.
• Various components like proteins, carbohydrates, teichoic acids, and DNA contribute to staphylococcal biofilms.
• Biofilm formation enhances resistance to antibiotics and host immune defenses, aiding the organism in evading clearance.

2. Poly-γ-glutamic Acid (PGA):

• The cap operon gene in S. capitis directs the synthesis of PGA, a second exopolysaccharide crucial for disease pathogenesis.
• PGA plays a significant role in resisting host antimicrobial peptides and reducing susceptibility to phagocytosis.

3. Endopeptidase ALE-1:

• A 25-kDa zinc-containing metallopeptidase, endopeptidase ALE-1, is encoded by a plasmid, along with the life gene responsible for immunity.
• Synthesized as a preproenzyme, endopeptidase ALE-1 becomes fully active after the removal of the N-terminal leader sequence and release of propeptides.
• This Class IIIa staphylococcin exhibits antimicrobial properties by hydrolyzing glycine-glycine bonds in peptidoglycan.

4. Phenol-soluble Modulins and Exoproteins:

• Phenol-soluble modulins (PSM), secreted amphipathic peptides, play multiple roles in S. capitis pathogenicity.
• PSMs are pro-inflammatory, possess cytolytic properties contributing to biofilm development, and exhibit antimicrobial activity.
• S. capitis also encodes various exoproteins, including proteases like ClpP and SepA, as well as hemolysins, lipases, and esterases.
• These proteins likely aid in immune evasion, host colonization, and persistent infections.

Pathogenesis

While S. capitis is primarily a commensal organism, its involvement in hospital-acquired infections becomes significant in individuals with compromised immune systems. The pathogenesis is driven by a collaboration of various proteins, surface-associated adhesins, and extracellular proteins acting as virulence factors. Although the precise infection mechanism remains not fully elucidated, similarities with other coagulase-negative Staphylococcal species, such as S. epidermidis and S. lugdunensis, are assumed. The pathogenesis of S. capitis infections unfolds as follows:

Attachment/ Adhesin/ Colonization:

• The initial step in S. capitis pathogenesis involves attachment to the host cell surface.
• Cell-surface adhesins like SdrF, SdrG, and SdrH act as fibrinogen-binding molecules, facilitating attachment to host cell fibrinogen.
• In surgical wounds, these adhesion mechanisms enable the bacterium to adhere to deeper tissues and implanted devices.
• Medical devices, such as valve implants and catheters, get coated with host-derived plasma proteins, extracellular matrix proteins, and coagulation products after S. capitis adhesion.
• Wall teichoic acid enhances initial adhesion to medical devices by binding to adsorbed fibronectin.
• Autolysin encoded by the atlL gene contributes to cell separation and stress-induced autolysis, contributing to biofilm formation.
• Poly-γ-glutamic acid, an exopolysaccharide produced by the organism, decreases susceptibility to immune cells and phagocytosis by binding to phagocytic cells.

Biofilm Formation:

• Biofilm formation is a crucial aspect of S. capitis pathogenesis.
• Following attachment, biofilm accumulation occurs through the production of a poly-N-acetylglucosamine (PNAG) homopolymer, promoting intercellular adhesion.
• PNAG production relies on the ica locus identified in the genome of S. capitis.
• The plasmin-sensitive protein Pls of S. capitis enhances cell-cell interaction, facilitating biofilm formation.
• Phenol-soluble modulins and exoproteins contribute to cytolytic activities and increase extracellular matrix.
• The biofilm serves as a protective barrier against immune cells and other microorganisms.
• It aids the organism in adapting to changing environmental conditions, including pH and temperature.

Clinical Manifestations

• While Staphylococcus capitis has not traditionally been considered a pathogenic organism, recent associations with nosocomial infections suggest its potential as an opportunistic pathogen.
• Nosocomial infections linked to medical implant devices such as artificial valves, catheters, and prosthetic joints have been reported.
• Although generally mild, untreated infections may progress to bacteremia and septic shock, posing a potential risk.
• Neonates are particularly susceptible, experiencing common and severe cases of bacteremia and sepsis caused by S. capitis.
• Additional infections, including endocarditis, myocarditis, and pericardial effusions, are also observed.
• Patients with these infections may exhibit symptoms such as prostration, high fever, hypotension, and shock, stemming from both the septic state and cardiac failure.
• Peripheral organ complications are often a result of embolic lesions, leading to skin abscesses, retinal emboli, as well as abscesses in the brain and spleen.

Lab Diagnosis

The laboratory diagnosis of infections attributed to S. capitis initiates with the collection of samples, including scabs, joint aspirates, and pus from deep sites. Microscopic examination of these samples serves as the initial observation. The focus of diagnosis primarily revolves around identifying the organism, leading to the following diagnostic approaches:

1. Cultural and Biochemical Characteristics:

• Culturing the organism on selective media, coupled with observing colony morphology, forms the basis of identification.
• Isolation on selective media, such as blood agar supplemented with 5 percent sheep blood, followed by incubation, typically 18–24 hours at 35–37°C.
• Biochemical tests on isolated colonies aid in species determination based on microscopic observation, colony morphology, and biochemical characteristics.

2. Rapid Identification Kits:

• Clinical laboratories often employ commercial identification kits or automated instruments for swift bacterial species determination.
• Microbial cellular fatty acid compositions, utilized in identification, are commonly employed.
• Automated systems like MicroScan Conventional Pos ID, Rapid Pos ID, and BBL Crystal Gram-Pos ID are prevalent for Staphylococcal species identification.

3. Molecular Diagnosis:

• Molecular methods involve tests targeting bacterial identification at the molecular level, utilizing unique nucleic acid sequences.
• Polymerase Chain Reaction (PCR) is a crucial molecular method, enabling the amplification and detection of bacterial DNA.
• DNA sequencing determines the bacterial DNA sequence for accurate identification.
• Ribotyping, employing rRNA restriction fragment polymorphism methods, is another molecular technique for detailed identification.

Treatment

• S. capitis is generally considered responsive to nafcillin, cephalosporins, and vancomycin, with or without rifampin.
• For endocarditis caused by S. capitis, cefalotin is the primary treatment choice; however, daptomycin may be used in cases of acute necrosis.
• Treatment is generally straightforward due to the typically mild nature of infections, and most S. capitis strains are susceptible to a broad range of antibiotics.
• However, the formation of biofilms can increase the organism's resistance to these drugs.
• Ongoing efforts are exploring new approaches to develop antimicrobials targeting different molecular pathways.

Prevention

The organism's biofilm-forming capability and its potential to cause sepsis in neonates highlight the importance of adopting preventive measures against S. capitis. The following strategies can be implemented to avoid infections by S. capitis:

• Applying biomaterial coatings on medical devices can prevent the organism from attaching to these devices.
• Regular wound cleaning and consistent dressing practices should be implemented to prevent infections in affected areas.
• Maintaining a clean hospital environment is crucial to prevent nosocomial infections.