Staphylococcus capitis- An Overview

Staphylococcus capitis is a bacterium that belongs to the genus Staphylococcus, which comprises Gram-positive, spherical cells that usually form clusters resembling grapes. Staphylococcus capitis is one of the coagulase-negative staphylococci (CoNS), meaning it does not produce the enzyme coagulase that can clot plasma. Coagulase-negative staphylococci are generally less virulent than coagulase-positive species, such as Staphylococcus aureus. However, they can still cause human infections, especially in immunocompromised patients or those with implanted medical devices.

Staphylococcus capitis was first isolated from human skin in 1975 by Kloos and Schleifer, who named it after the Latin word for head, "caput," because it was found to be more prevalent on the scalp and face than other body sites. Later, it was divided into two subspecies based on their urease activity, acid production from maltose, fatty acid profile, colony size, and DNA sequence: S. capitis subsp. capitis and S. capitis subsp. ureolyticus. The former is more common on human skin, while the latter is more frequently isolated from primates and the external auditory meatus of adults.

Staphylococcus capital is part of the normal flora of the skin and mucous membranes of humans and other warm-blooded animals, where it usually does not cause any harm. However, it can also be an opportunistic pathogen that can cause infections in various sites, such as the bloodstream, heart valves, joints, bones, and central nervous system. These infections are often associated with foreign bodies, such as prosthetic valves, catheters, shunts, or prosthetic joints, which provide a surface for the bacteria to adhere to and form biofilms. Biofilms are complex communities of bacteria embedded in a matrix of extracellular substances that protect them from host defenses and antibiotics. Staphylococcus capitis can also produce various virulence factors, such as exopolysaccharides, endopeptidases, phenol-soluble modules, and exoproteins, that contribute to its pathogenicity by facilitating adhesion, immune evasion, tissue damage, and antimicrobial resistance.

Staphylococcus capitis infections are usually diagnosed by culturing the bacteria from clinical specimens, such as blood, pus, or joint fluid, and performing biochemical tests or molecular methods to identify the species and subspecies level. The treatment of S. capitis infections depends on the site and severity of infection, as well as the susceptibility of the bacteria to different antibiotics. In some cases, removal or replacement of the infected device may be necessary to eradicate the infection. Preventing S. capitis infections involves:

Maintaining a clean hospital environment.

Practicing good hygiene and infection control measures.

Coating medical devices with antimicrobial agents to prevent bacterial colonization.

In summary, Staphylococcus capitis is a Gram-positive, coagulase-negative coccus that is part of the normal flora of human skin but can also cause opportunistic infections in certain conditions. It is a biofilm-forming bacterium that can adhere to medical devices and produce various virulence factors that enhance its pathogenicity. It can be diagnosed by culture and identification methods and treated with antibiotics or device removal. Prevention strategies include hygiene and infection control measures and antimicrobial coating of devices.

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Staphylococcus capitis is a Gram-positive, coagulase-negative coccus that belongs to the genus Staphylococcus, which comprises more than 50 species and subspecies. Staphylococcus is classified into the phylum Bacillota, class Bacilli, Order Bacillales, and family Staphylococcaceae.

The cell wall composition, G + C content of DNA, DNA-DNA hybridization, 16S rRNA sequence similarities, and genome sizes are used to classify staphylococcal species. Members of the same species have relative DNA-binding values that are generally 70% or higher, whereas organisms from different species have relative DNA-binding values that are less than 70%.

Staphylococcus capitis was first isolated from healthy human skin in 1975 and classified as a coagulase-negative Staphylococcus species (CoNS) by Kloos and Schleifer. S. capitis is frequently found on the human scalp and the forehead and thrives in lipid-rich areas with abundant sebaceous glands.

S. capitis is further classified as two subspecies based on various characteristics; S. capitis subsp. capitis and S. capitis subsp. ureolyticus. The former was also identified by Kloos and Schleifer in 1975, while the latter was discovered by Bannerman and Kloos in 1991. The subspecies differ in their urease activity, ability to produce acid from maltose in anaerobic conditions, fatty acid profile, larger colony size, and DNA sequence differentiation.

The following is the taxonomical classification of S. capitis:

| Domain | Bacteria |

| --- | --- |

| Phylum | Bacillota |

| Class | Bacilli |

| Order | Bacillales |

| Family | Staphylococcaceae |

| Genus | Staphylococcus |

| Species | S. capitis |

| Subspecies | S. capitis subsp. capitis <br> S. capitis subsp. ureolyticus |

: Kloos WE, Schleifer KH (1975) Isolation and characterization of staphylococci from human skin I. Amended descriptions of Staphylococcus epidermidis and Staphylococcus saprophyticus and descriptions of three new species: Staphylococcus cohnii, Staphylococcus haemolyticus, and Staphylococcus xylosus. Int J Syst Bacteriol 25:50–61

Staphylococcus capitis is a part of the normal flora of the skin of the human scalp, face, neck, scrotum, and ears. It is also found in the external auditory meatus of adults. The species is further divided into two subspecies: S. capitis subsp. capitis and S. capitis subsp. ureolyticus, which have different preferences and habitats.

S. capitis subsp. capitis is the primary host of human capital, whereas S. capitis subsp. ureolyticus is the primary host of primates. S. capitis subsp. Capital strongly prefers the human head, whereas S. capitis subsp. ureolyticus has a moderate preference for the same. The increase in S. capitis populations on the scalp after puberty is linked to increased sebaceous gland activity during puberty.

Adults` external auditory meatus also contains S. capitis subsp. ureolyticus.lacks urease activity due to the low urea concentration. Despite their preference for the head, S. capitis can be found in other parts of the body, such as the arms and legs.

S. capitis can also colonize medical devices such as prosthetic valves, catheters, and prosthetic joints, which can form biofilms and cause infections. It can also enter the bloodstream through wounds or venipuncture and cause bacteremia and sepsis, especially in neonates and immunocompromised patients.

S. capitis is a non-motile, non-spore-forming, Gram-positive coccus with an average diameter of 0.8–1.2 μm. The cells occur in pairs and are frequently found in tetrads due to their division in multiple planes to form irregular grapelike clusters. The cells are facultatively anaerobic, and the strains of S. capitis are encapsulated in various ways.

The cell wall comprises peptidoglycan and teichoic acid in the dry weight ratio of approximately 60–30 percent, respectively. The peptidoglycan is the main structural polymer in the cell wall, and it is essential for maintaining the cell`s spherical shape. The cell membrane is a lipid-protein bilayer composed of phospholipids, glycolipids, menaquinones, and carotenoids, with cell membrane-associated proteins including adenosine triphosphatase, polyprenolphosphokinase, various oxidases and dehydrogenases, and several penicillin-binding proteins.

Some of the cell-wall-associated S. capitis proteins have been identified and shown to promote adherence to extracellular matrix proteins and soluble plasma components. a few of these proteins belong to the Sdr family of proteins, including SdrF, SdrG, and SdrH, which act as fibrinogen-binding molecules. These proteins facilitate the attachment and colonization of S. capitis on the host surface or medical devices.

: Microbiology: An Introduction (13th Edition) by Gerard J. Tortora et al.

: Staphylococcus capitis: from commensal to opportunistic pathogen

: Fibrinogen-binding properties of a novel Staphylococcus capitis subsp. urealyticus MSCRAMM

Staphylococcus species can be grown on a variety of agar and liquid media, which aids in their identification. Identify and selectively grow the organism. These organisms can grow in multiple sets of culture media like nutrient agar, Mannitol Salt Agar, P agar, and thioglycollate medium. Depending on various cultural characteristics like growth patterns and colony morphology, species-level identification can be made. The following are the colony morphology of S. capitis on different media:

• Nutrient agar (NA): Circular, cream-colored to white colonies of S. capitis are observed on NA. The colonies have raised elevations and a dense center with transparent borders. The colonies are mostly 1 mm in diameter with an entire margin.

• Mannitol Salt Agar (MSA): Yellow colonies of the size 1-3 mm are seen, which are surrounded by yellow zones indicating the release of acid as a result of mannitol utilization.

• P agar: S. capitis subsp. S. capitis subsp. capital: White or greyish colonies of the size 1-3mm in diameter that are smooth, slightly convex, glistening, and opaque are seen on P agar. The color might change to yellow or yellow-orange after storage at 1-4°C. Ureolyticus: Raised, opaque, glistening colonies are seen on P agar. Some strains develop yellow pigmentation after late incubation. Colonies may be smooth or rough and have slightly irregular or entire edges. The colony diameter is about 4.3–7.1 mm.

• **Wrinkled, medium-sized (1-4 mm in diameter), -hemolytic, opaque, rough white colonies are observed on blood agar (BA). On blood agar, colony pleiomorphism is common. After 48 hours of incubation, there is obvious hemolysis. Hemolysis does not occur in S. capitis subsp. ureolyticus.

The biochemical characteristics of S. capitis are the metabolic and enzymatic reactions that the bacteria perform under different conditions. These characteristics help identify and differentiate S. capitis from other staphylococcal species and other bacteria. 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. | Coagulase | Negative (-) |

| 6. | Hemolysis | Variable |

| 7. | Urease | Variable |

| 8. | Nitrate reduction | Positive (+) |

| 9. | Mannitol fermentation | Positive (+) |

| 10. | Glucose fermentation | Positive (+) |

| 11. | Lactose fermentation | Negative (-) |

| 12. | Sucrose fermentation | Negative (-) |

| 13. | Maltose fermentation | Variable |

| 14. | Novobiocin susceptibility | Susceptible |

S. capitis subsp. ureolyticus can be distinguished from S. capitis subsp. Capital by producing urease, the ability to produce acid from maltose, and fatty acid composition.

Coagulase-negative Staphylococci generally have a lower virulence potential compared to the most virulent staphylococcal species, S. aS. capital, on the other hand, encodes for several factors predicted to be important for biofilm production, persistence, and immune evasion. These virulence factors are primarily responsible for protecting the organism from the host immune system and developing resistance to various groups of microbial agents. Furthermore, S. capitis is linked to an endopeptidase that acts as a bacteriocin.

• Biofilm formation: Biofilm is a multicellular composite of the bacterial cell and extracellular matrix that provides S. capitis, on the other hand, encodes for several factors predicted to be important for biofilm production, persistence, and immune evasion. These virulence factors are primarily responsible for protecting the organism from the host immune system and developing resistance to various groups of microbial agents. Furthermore, S. capitis is linked to an endopeptidase that acts as a bacteriocin. Produces a poly-N-acetyl glucosamine (PNAG) homopolymer, facilitating intercellular adhesion between the species. PNAG production depends on the ica locus; S. capitis genome has recently been discovered. Plus, the plasmin-sensitive protein of S. capitis promotes cell-cell interaction and the process of cell accumulation to form a biofilm. Pls is thought to have a similar domain structure and sequence homology to S. epidermis accumulation-associated protein (AAP). Proteins, carbohydrates, teichoic acids, and DNA have all been identified as constituents of staphylococcal biofilms. As a result, various biofilm-associated genes and operons play roles in the four stages of biofilm growth, namely adherence (primary attachment), accumulation, maturation, and dispersal, which have been identified in S. capitis as well. Biofilm development allows for the deep-sited cells to become more resistant to administered antibiotics and the body`s natural mechanisms, interfering with attempts by the host immune system to clear the infection.

• Poly--glutamic acid: During the genome analysis of S. capitis, another gene coding for the cap operon was found, which mediates the production of a second exopolysaccharide, poly--glutamic acid (PGA). PGA plays an important role in disease pathogenesis, specifically resistance to host antimicrobial peptides and reduced phagocytosis susceptibility.

• Endopeptidase ALE-1: Endopeptidase ALE-1 is 25-kDa, zinc-containing metallopeptidase encoded by a plasmid containing the life gene responsible for immunity. Endopeptidase is synthesized as a pre-proenzyme, and the N-terminal leader sequence is removed during secretion. At the same time, 15 tandem repeats of propeptides, also at the N-terminus, are released by extracellular cysteine peptidase, yielding a fully active enzyme. Endopeptidase has antimicrobial property that hydrolyses glycine-glycine bonds present in the peptidoglycan of different microorganisms. It makes up the Class IIIa staphylococcus comprising large, heat-labile proteins.

• Exoproteins and Phenol-soluble Modulins: Phenol-soluble modules (PSMs) are secreted amphipathic peptides that appear to play multiple roles in S. capitis pathogenicity. PSMs promote inflammation, possess cytolytic properties that contribute to biofilm development, and have antimicrobial activity. S. capitis also encodes for a suite of exoproteins that likely contribute to infection, which include proteases such as ClpP, which is involved in biofilm formation, and SepA, which degrades host antimicrobial peptides, as well as hemolysins, lipases, and esterases. These proteins likely facilitate immune evasion, host colonization, and persistence.

As S. capitis is a commensal, it rarely causes diseases; however, it involves Various hospital-acquired infections in people with weakened immune systems. To cause such infections, various proteins, surface-associated adhesins, and extracellular proteins collaborate as virulence factors. The exact mechanism of infection in the case of S. capitis is still unknown. Still, it is assumed to be S. epidermidis and S. lugdunensis are two coagulase-negative Staphylococcal species. The pathogenesis of S. capitis infections can be summarized as follows:

• Attachment/ Adhesin/ Colonization: The first step in the pathogenesis of S. capitis is attachment to the host cell surface. SdrF, SdrG, and SdrH are cell-surface adhesins that act as fibrinogen-binding molecules, allowing attachment to the fibrinogen present, in the host cell. The bacterium utilizes these adhesion mechanisms in a surgical wound to adhere to the deeper tissues and the implanted device. When S. capitis adheres to medical devices such as valve implants and catheters, the surface of the device becomes coated with host-derived plasma proteins, extracellular matrix proteins, and coagulation products (platelets and thrombin). By binding to adsorbed fibronectin, teichoic wall acid improves S. capital`s initial adhesion to medical devices. The initial attachment is quickly followed by an irreversible attachment. one strengthened by molecule-specific adhesins. Besides, autolysin encoded by the atlL gene in the organism is involved in cell separation and stress-induced autolysis, contributing to the formation of a biofilm. An exopolysaccharide produced by the organism, poly--glutamic acid, decreases susceptibility towards the immune cells and phagocytosis as the polysaccharide binds to the phagocytic cells.

• Biofilm formation: Cell surface attachment is required. Followed by biofilm formation, which is the most important part of pathogenesis by S. capitis. Following attachment, biofilm accumulation in staphylococci typically produces a poly-N-acetyl glucosamine (PNAG) homopolymer, facilitating intercellular adhesion between the species. PNAG production depends on the ica locus, recently identified in the genome of S. capitis. The plasmin-sensitive protein Pls of S. capitis further promotes cell-cell interaction and aids biofilm formation. It is further supported by phenol-soluble modules and exoproteins, which are involved in cytolytic activities and help increase theExtracellular matrix (XCM). The biofilm acts as a barrier against various immune cells and microorganisms in the environment. It also assists the organism in adapting to changing environmental conditions such as pH and temperature.

S. capitis is a commensal bacterium that rarely causes diseases in healthy individuals. However, it can cause opportunistic infections in immunocompromised patients or those with indwelling medical devices. Some of the clinical manifestations of S. capitis infections are:

• Bacteremia and sepsis. S. capitis can enter the bloodstream through contaminated catheters, wounds, or surgical sites and cause bacteremia, which is the presence of bacteria in the blood. Bacteremia can lead to sepsis, a life-threatening condition characterized by systemic inflammation and organ dysfunction. Sepsis caused by S. capitis is more common in neonates, especially those with low birth weight or premature birth. Symptoms of sepsis include fever, chills, rapid breathing, low blood pressure, confusion, and organ failure.

• Endocarditis. Endocarditis is an infection of the inner lining of the heart (endocardium) or the heart valves. S. capitis can cause endocarditis by adhering to damaged or artificial heart valves and forming biofilms that resist antibiotic treatment. Endocarditis can result in valve dysfunction, heart failure, embolism, or abscess formation. Symptoms of endocarditis include fever, heart murmur, chest pain, shortness of breath, fatigue, night sweats, and weight loss.

• Urinary tract infection (UTI). UTI is an infection of the urinary system, including the kidneys, ureters, bladder, or urethra. S. capitis can cause UTI by ascending from the urethra to the bladder or spreading from the bloodstream to the kidneys. UTI can cause symptoms such as burning or pain during urination, increased frequency or urgency of urination, blood or pus in the urine, lower abdominal pain, back pain, fever, and nausea.

• Skin and soft tissue infection (SSTI). SSTI is an infection of the skin or underlying tissues, such as muscles or fat. S. capitis can cause SSTI by invading through breaks in the skin or by spreading from other sites of infection. SSTI can manifest as boils, abscesses, cellulitis, impetigo, wound infections, or surgical site infections. Symptoms of SSTI include redness, swelling, warmth, pain, pus drainage, and fever.

The collection of samples, in this case, scabs, joint aspirates, and pus aspirated from deep sites, is the first step in the lab diagnosis of S. capitis infections. The first observation is a close look at these samples under the microscope. The diagnosis is mostly concerned with identifying the organism; thus, it is mostly concerned with identifying the organism.

Cultural characteristics and Biochemical characteristics

• Culturing the organism on different selective media and observing the colony morphology on these media provides a basis for identifying the organism.

• This also limits the scope of diagnosis and makes the process more feasible.

• Isolation of the organism from primary clinical specimens is achieved on selective culture media like blood agar supplemented with 5 percent sheep blood, following an incubation period of 18–24 h in the air at 35–37°C.

• The isolated colonies are then subjected to different biochemical tests, which help determine species.

• Depending on the microscopic observation, colony morphology, and biochemical tests, S. capitis can be detected.

• Rapid identification kits

• Many clinical laboratories have started to employ different commercial identification kits or automated instruments that allow rapid determination of bacterial species.

• Microbial cellular fatty acid compositions are used to identify S. capitis.

• Some common automated systems for Staphylococcal species identification include MicroScan Conventional Pos ID, Rapid Pos ID, and BBL Crystal Gram-Pos ID.

• Molecular diagnosis

• Molecular methods of bacteria diagnosis usually include tests that help identify the organism at a molecular level.

• This method utilizes the unique set of nucleic acid sequences present in each organism, providing a more detailed and accurate identification.

• One of the most important molecular methods is Polymerase Chain Reaction (PCR) which helps amplify and detect bacterial DNA.

• Besides, DNA sequencing is performed to determine the DNA sequence of the bacteria that can be used for identification.

• Ribotyping is another molecular method involving rRNA restriction fragment polymorphism methods.

The treatment of infections caused by S. capitis depends on the type, location, and severity of the infection, as well as the susceptibility of the bacteria to antibiotics. The following are some general principles of treatment for S. capitis infections:

• Antibiotics. Antibiotics are the mainstay of treatment for staph infections. However, some strains of S. capitis have become resistant to common antibiotics, such as penicillins and cephalosporins. Therefore, it is important to perform tests to identify the specific strain of S. capitis and its antibiotic sensitivity before starting treatment. Antibiotics commonly prescribed to treat staph infections include cefazolin, nafcillin, oxacillin, vancomycin, daptomycin, and linezolid. Vancomycin may be required for serious staph infections, such as endocarditis or bacteremia. The duration of antibiotic therapy may vary depending on the type and extent of infection. Still, it usually ranges from 7 to 14 days for uncomplicated skin infections to 4 to 6 weeks for endocarditis or osteomyelitis.

• Wound drainage. If the infection involves a skin lesion, such as a boil or an abscess, the health care provider may cut (incision) into the sore to drain fluid that has collected. This helps to relieve pain and pressure and speed up healing. The wound may be covered with a sterile dressing and bandage to prevent further infection.

• Device removal. If the infection is associated with a medical device, such as a catheter, a prosthetic joint, or a heart valve, the device may need to be removed or replaced. This is because the device may serve as a source of persistent infection and biofilm formation by S. capitis. Biofilms are communities of bacteria that adhere to surfaces and are protected by a slimy layer of polysaccharides and proteins. Biofilms make bacteria more resistant to antibiotics and immune system attacks. Removing or replacing the device may help to eradicate the infection and prevent complications.

• Supportive care. In addition to antibiotics and surgical interventions, patients with staph infections may need supportive care to manage their symptoms and prevent complications. This may include pain relief medications, anti-inflammatory drugs, fluids and electrolytes for dehydration, blood pressure medications for hypotension, oxygen therapy for respiratory distress, and blood transfusions for severe anemia. Patients with staph infections should also practice good hygiene and wound care to prevent spreading the infection to others or reinfecting themselves.

Staphylococcus capitis is a commensal bacterium that rarely causes infections, but it can become opportunistic and cause serious complications in immunocompromised patients or those with medical devices. Therefore, it is important to prevent the transmission and colonization of S. capitis as much as possible. Some of the preventive strategies that can be followed are:

• Wash your hands. This is the most effective way to reduce the risk of getting staph infections. Wash your hands with soap and water for at least 20 seconds, especially before and after touching broken skin, wounds, or medical devices.

• Keep wounds clean and covered. If you have a cut, scrape, or surgical incision, clean it regularly with an antiseptic solution and cover it with a sterile bandage until it heals. This will prevent S. capitis from entering the deeper tissues or the bloodstream.

• Avoid sharing personal items. Do not share towels, razors, clothing, or other items that may contact your skin or body fluids. This will prevent the spread of S. capitis from one person to another.

• Coat medical devices with biomaterials. Some studies have suggested that coating medical devices such as catheters, valves, or prosthetic joints with antimicrobial biomaterials can prevent the attachment and biofilm formation of S. capitis on these surfaces. This may reduce the risk of device-related infections by S. capitis.

• Screen high-risk patients and decolonize them if needed. Some patients may be more prone to S. capitis infections, such as those in intensive care units (ICUs), those undergoing surgery, or those using invasive devices. These patients may benefit from screening for S. capitis colonization and decolonization if positive. Decolonization may involve topical antiseptics such as chlorhexidine or mupirocin to the skin or nasal passages or the oral administration of antibiotics such as rifampin or linezolid.

• Treat infections appropriately and rapidly. If S. capitis infection occurs, it is important to diagnose it accurately and treat it promptly with appropriate antibiotics and clean the infected area. Some strains of S. capitis may resist common antibiotics, so culture and sensitivity testing may be needed to determine the best antibiotic regimen. Delayed or inadequate treatment may lead to complications such as bacteremia, sepsis, endocarditis, or abscesses.

By following these preventive measures, S. capitis infections can be reduced and controlled effectively.

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