Staphylococcus hominis- An Overview

Staphylococcus hominis is a member of the bacterial genus Staphylococcus, which consists of Gram-positive, spherical cells that form clusters. The genus Staphylococcus is classified into different species based on various characteristics, such as DNA-DNA hybridization, fatty acid composition, G+C content, and biochemical reactions .

Staphylococcus hominis is further divided into two subspecies: S. hominis subsp. hominis and S. hominis subsp. novobiosepticus. These subspecies are distinguished by their susceptibility to novobiocin, an antibiotic that inhibits DNA gyrase, and their habitat .

S. hominis subsp. hominis consists of strains that are susceptible to novobiocin and are primarily found on the human skin surface, especially in areas with apocrine glands, such as the axillae and the pubic region . These strains are part of the normal skin flora and usually do not cause infections unless the host is immunocompromised or has a medical device implant.

S. hominis subsp. novobiosepticus consists of strains that are resistant to novobiocin and can be isolated from blood cultures of patients with sepsis or endocarditis . These strains are more virulent and more resistant to other antibiotics than S. hominis subsp. hominis. They can cause serious infections in neonates, cancer patients, and patients with artificial valves.

The following table summarizes the main differences between the two subspecies of S. hominis:

• Humans are the primary host for both of the subspecies of S. hominis as these are mostly found as commensal organisms on the skin surface .
• While other coagulase-negative Staphylococci like S. epidermidis colonize the upper part of the body, S. hominis is mostly found on the lower part of the body like the perineal and groin areas .
• It is found in a large number in areas with numerous apocrine glands that retain some amount of moisture .
• In a recent study, it was found that S. hominis account for about 22% of all Staphylococci species found on the human skin.
• Besides, these are also found on the scalp of preadolescent children along with other species of Staphylococci like S. capitis.
• S. hominis, unlike other Staphylococci species like S. lugdunensis, is found in virtually all parts of the body in different numbers. The numbers also change over a few weeks as they tend to colonize certain areas for a shorter period of time.
• S. hominis is also identified as the most abundant bacterial species in the human underarm region.

Both the species of S. hominis are Gram-positive, nonmotile, non-spore-forming cocci with an average size of 1.0–1.5 μm in diameter . The arrangement of the cells is characteristic of all Staphylococci species where the organisms occur singly or form tetrads and smaller numbers of pairs. This arrangement is due to the property of the organism to divide in more than one plane to form irregular grapelike clusters.

These are facultatively anaerobic but show weak and delayed growth under anaerobic conditions. Unlike coagulase-positive Staphylococci like S. aureus, S. hominis doesn’t have a capsule surrounding the cell wall. The cell wall, however, is composed of characteristic peptidoglycan and teichoic acid that provides shape and protection to the cell. The cell membrane is made up of a lipid-protein bilayer composed of peptidoglycan and other proteins. Like all other coagulase-negative Staphylococci, S. hominis also has fewer cell wall adhesions and cell-wall associated proteins.

The selective media for most Staphylococci species includes media like P agar, Mannitol Salt Agar, Baird-Parker agar, and liquid medium like thioglycollate medium. Even though the organism is facultatively anaerobic, it shows weak or delayed growth under anaerobic conditions. The optimum temperature for growth is 37°C, but some growth is seen from 20°C to 45°C. Sufficient growth can be seen at 10% NaCl with decreased growth at 15%.

The following is the colony morphology observed on different media:

• Nutrient Agar (NA): Circular, cream-colored to white colonies of S. hominis are observed on NA. The colonies are mostly 1mm in diameter with an entire margin. The colonies have raised elevation and a dense center with transparent borders.
• Mannitol Salt Agar (MSA): Small pink to red colonies are formed on MSA. The media remains red as the bacterium cannot ferment mannitol. The colonies are 1-2 mm in diameter with an entire margin.
• P agar: S. hominis subsp. hominis: Colorless to cream to yellow-orange colonies of diameter 3-5 mm are seen on P agar. The colonies are smooth, opaque, raised to umbonate, and butyrous, with entire margins. S. hominis subsp. novobiosepticus: Grayish-white, convex to umbonate, butyrous, and opaque colonies, with entire margins. Colonies of the size 4–6 mm in diameter after incubation at 34–35°C for three days.

The biochemical characteristics of S. hominis can be used to differentiate it from other Staphylococci species and also to identify the subspecies of S. hominis. Some of the common biochemical tests and their results for S. hominis are as follows:

• Capsule: S. hominis does not have a capsule surrounding the cell wall.
• Shape: S. hominis is a coccus-shaped bacterium.
• Catalase: S. hominis is catalase-positive, meaning it can produce bubbles when exposed to hydrogen peroxide.
• Oxidase: S. hominis is oxidase-negative, meaning it does not produce a color change when exposed to an oxidizing agent.
• Coagulase: S. hominis is coagulase-negative, meaning it does not cause blood clotting.
• Novobiocin susceptibility: S. hominis subsp. hominis is susceptible to novobiocin, an antibiotic that inhibits DNA gyrase, whereas S. hominis subsp. novobiosepticus is resistant to novobiocin .
• Arginine dihydrolase: S. hominis subsp. hominis can utilize arginine as a source of energy and produce ammonia, whereas S. hominis subsp. novobiosepticus cannot utilize arginine.
• Fermentation: S. hominis, as well as most other staphylococcal species common on the human skin, is able to produce acid aerobically from glucose, fructose, sucrose, trehalose, and glycerol. Some strains were also able to produce acid from turanose, lactose, galactose, melezitose, mannitol, and mannose.

• Enzymatic reactions: S. hominis can produce various enzymes that are involved in different metabolic pathways or virulence factors. Some of these enzymes are:

  • Urease: S. hominis can produce urease, an enzyme that hydrolyzes urea into ammonia and carbon dioxide.
  • Lipase: S. hominis can produce lipase, an enzyme that hydrolyzes fats into glycerol and fatty acids.
  • DNase: S. hominis can produce DNase, an enzyme that degrades DNA into nucleotides.
  • Hemolysin: S. hominis can produce hemolysin, a toxin that lyses red blood cells.

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

The exact mechanism of infections caused by S. hominis is yet not known, but it has been seen that are several factors present in the species assist in the process of infection. These virulence factors have also been a topic of interest for many research works as the organism is increasingly becoming more resistant to various antibiotics like aminoglycosides. Some of the virulence factors of S. hominis are:

• Adhesins: The colonization of the surface is the first step towards the pathogenesis of infections caused by S. hominis. In the case of Staphylococcus species, adhesion to host tissue is achieved by a large family of surface proteins that bind with varying degrees of specificity to host matrix proteins, such as fibronectin, fibrinogen, vitronectin, laminin, and von Willebrand factor present on the host cell. This attachment followed by colonization is brought about by various proteins and cell-wall associated proteins that allow the binding of the bacteria to the cell surface. One of the most important binding proteins is the fibrinogen-binding protein found in most of the coagulase-negative staphylococci. Staphylococci surface protein (Ssp) and autolysin protein (Aas) are two cell-wall associated proteins that have the ability to bind with the fibrinogen present on the host cell surface. Strains of S. hominis have an excellent ability to bind to the HeLa cells in patients that have undergone chemotherapy. The exact mechanism of the binding is not yet known.

• Invasion of epithelial cells: Once the bacteria bind to the surface of the host cell, it then has the ability to invade the cells by release an extracellular protein that has cytotoxic activity. The range of toxicity might differ between different strains, but it is known to affect both the epithelial cells and the HeLa cells. The ability of the organism to cause invasion of epithelial cells is considered the primary mechanism for the entry of the bacteria into the bloodstream, causing sepsis and shock syndromes.

• Genes providing antibiotic resistance: MecA gene found in various bacteria is considered a major gene that provides antibiotic resistance to the bacteria against various groups of antibiotics. The mecA gene encodes a penicillin-binding protein, and as a result of mecA expression, beta-lactam antibiotics are not effective against such antibiotics. MecA gene has been recently found in the genome of S. hominis, which indicates the ability of the organism to cause infections similar to other MRSA. Besides, other genes like ant(4′)–Ia, aac(6′)/aph(2″) and aph(3′)–IIIa have also been seen in S. hominis which is probably the reason for the resistance of the organism against aminoglycosides.

• Biofilm: Biofilm formation is an important virulence factor for most coagulase-negative Staphylococci that cause infections related to medical device implants. A biofilm is a layer composed of bacteria living in an aggregated structure as cellular clusters or microcolonies along with extracellular matrices either release by the organism or derived from the environment. The biofilm is encapsulated in a matrix composed of an extracellular polymeric substance and is often separated by open water channels. These channels act as a circulatory system to deliver nutrients and remove metabolic waste products in and out of the biofilms. The biofilm allows bacteria to adhere to inert materials and also results in increased antibiotic resistance. Infections related to catheters and artificial valves have also been seen in the case of S. hominis, which are mostly caused due to the ability of the organism to form biofilms. Biofilms provide protection to the bacterial species against both the immune cells as well as the molecules of the antimicrobial drugs. Besides, it also helps the bacteria to adjust to the changing environmental factors.

Infections associated with S. hominis are mostly nosocomial or hospital-acquired. These infections usually occur in patients that are immunocompromised or have recently undergone chemotherapy. In the case of cancer patients, the target cells of S. hominis are the HeLa cells as it has the ability to colonize and invade such cells. The exact pathogenesis of the infections caused by S. hominis is not yet fully understood; however, it is known that the genome of the organism carries several gene sequences that aid the process of infection by this bacterium.

Attachment/ Adhesion/ Colonization

As a commensal, S. hominis is equipped with different surface proteins and molecules that aid in the process of attachment and colonization. One of the most important factors that support the attachment of the bacteria to epithelial cells is the Staphylococci surface protein (Ssp). Besides, there is an icaADBC-encoded polysaccharide intercellular adhesin (PIA) that further supports this attachment. The attachment of the bacteria to the cell surface enables the bacteria to colonize the surface and cause the invasion of the cells. Attachment is also the first step during the biofilm formation, which is further enhanced by various proteinaceous products that help in cell aggregation and binding with each other.

Epithelial cell invasion

Invasion of epithelial cells and HeLa cells is another mechanism of infection employed by S. hominis. It has been studied that the organism is capable of releasing different extracellular toxins that have cytopathic effects on the epithelial cells and the HeLa cells. The exact composition of the toxins is not yet known, but these might be similar to the cytotoxins released by S. aureus.

Resistance against antibiotics

S. hominis is capable of maintaining infections as it has various mechanisms that provide protection against different groups of antibiotics. MecA gene present in S. hominis is known to code for proteins that bind to penicillin or other such antimicrobial agents. This prevents the action of penicillin which provides resistance against such antibiotics. Besides, another group of genes consisting of ant(4′)-Ia gene are responsible for the resistance against aminoglycosides.

S. hominis is a commensal bacterium that usually does not cause any symptoms in healthy people. However, it can cause opportunistic infections in immunocompromised patients or those with medical devices implanted in their body. The symptoms of S. hominis infections depend on the type and location of the infection. Some of the common clinical manifestations of S. hominis infections are:

• Skin infections: S. hominis can cause various skin infections, such as boils, impetigo, cellulitis, and scalded skin syndrome. These infections are characterized by redness, swelling, pain, pus, blisters, and crusts on the affected skin area. Skin infections can spread to deeper tissues or the bloodstream if not treated promptly.
• Food poisoning: S. hominis can contaminate food and produce toxins that cause food poisoning. The symptoms of food poisoning include nausea, vomiting, diarrhea, dehydration, and low blood pressure. These symptoms usually appear within hours of eating the contaminated food and last for a few hours or days.
• Bacteremia: S. hominis can enter the bloodstream through wounds, catheters, or surgical sites and cause bacteremia or sepsis. This is a serious condition that can lead to organ failure and death if not treated quickly. The symptoms of bacteremia include high fever, chills, nausea, vomiting, rash, confusion, muscle aches, and diarrhea.
• Endocarditis: S. hominis can infect the inner lining of the heart (endocardium) and cause endocarditis. This is a rare but life-threatening complication that can damage the heart valves and lead to heart failure. The symptoms of endocarditis include fever, night sweats, weight loss, chest pain, shortness of breath, cough, blood in urine, and swollen limbs.
• Cavernous sinus thrombosis (CST): S. hominis can infect the cavernous sinus, a large vein at the base of the brain that drains blood from the face and eyes. This can cause a blood clot (thrombosis) that blocks the blood flow and puts pressure on the nerves and brain tissue. This is a rare but very serious condition that can cause permanent damage to the eyesight or brain function. The symptoms of CST include fever, severe headache, swelling around the eyes, weakness of the eye muscles, drooping eyelids, double vision, and severe eye pain.
  
  
  Lab diagnosis of Staphylococcus hominis

As with most bacterial infections, the collection of clinical specimens is the first step of laboratory diagnosis. In the case of S. hominis, clinical specimens like the scabs, joint aspirates, and pus aspirated from deep sites are to be collected. Diagnosis of disease in the case of S. hominis infections are mostly related to the identification of the organism.

The following are some methods used for the identification of S. hominis:

• Direct microscopic examination: This may provide a rapid, presumptive report of gram-positive cocci resembling staphylococci. Gram staining and catalase test can be performed on the specimens to differentiate S. hominis from other gram-positive cocci.
• Culture and biochemical characteristics: The specimens are inoculated on selective culture media like blood agar supplemented with 5 percent sheep blood, mannitol salt agar, or P agar. The colonies are observed for their size, shape, color, and hemolysis after incubation at 35–37°C for 18–24 hours. The colonies are further tested for their susceptibility to novobiocin, which can differentiate S. hominis subsp. hominis (susceptible) from S. hominis subsp. novobiosepticus (resistant). Other biochemical tests like fermentation of sugars and enzymatic reactions can also be performed to confirm the identity of S. hominis.
• Rapid identification kits: Many clinical laboratories have started to employ different commercial identification kits or automated instruments that allow rapid determination of bacterial species. In the case of S. hominis, microbial cellular fatty acid compositions are used for the identification. Some of the common automated systems for the identification of S. hominis include MicroScan Conventional Pos ID, Rapid Pos ID, and BBL Crystal Gram-Pos ID.
• Molecular diagnosis: A molecular diagnosis is now considered the basis for the identification as it can provide easy and detailed identification of the species and subspecies based on their nucleotide sequences. Real-time PCR and high-throughput DNA sequencing systems are the major molecular techniques used for the analysis of the nucleic acid sequences and identification of S. hominis. Besides, ribotyping is also a common practice that studies the rRNA by restriction fragment length polymorphism and allows molecular differentiation of S. hominis strains.

Treatment of infections caused by S. hominis is often challenging because of its resistance to different antimicrobial agents. Methicillin-resistant isolates and those resistant to other antimicrobials are particularly important because they have limited therapeutic options. Traditional antibiotic treatment protocols based on the standard in vitro susceptibility tests mostly designed for planktonic bacteria might not be applicable to eradicate biofilm-producing S. hominis infections. Thus, different treatment strategies are required depending on the type and severity of the infection.

Antibiotics

Antibiotics are the mainstay of treatment for S. hominis infections, but their choice and duration should be guided by the results of culture and susceptibility tests. Some of the commonly used antibiotics for S. hominis infections are:

• Glycopeptides: Glycopeptides, such as vancomycin and teicoplanin, are usually the treatment of choice for infections caused by methicillin-resistant S. hominis . They have a bactericidal activity against most coagulase-negative staphylococci and are effective against biofilm-associated infections. However, some cases of glycopeptide-resistant S. hominis have been reported, which may limit their use in the future.
• Daptomycin: Daptomycin is a lipopeptide antibiotic that has a rapid bactericidal activity against gram-positive bacteria, including methicillin-resistant S. hominis . It has a unique mechanism of action that disrupts the bacterial membrane potential and causes cell death. It also has anti-biofilm activity and can penetrate into infected tissues. Daptomycin may be an alternative to glycopeptides for the treatment of S. hominis infections, especially in cases of endocarditis or bacteremia .
• Linezolid: Linezolid is an oxazolidinone antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. It has a bacteriostatic activity against most gram-positive bacteria, including methicillin-resistant S. hominis . It has good oral bioavailability and tissue penetration, which makes it suitable for outpatient therapy or oral switch therapy . Linezolid may be used for the treatment of S. hominis infections involving skin and soft tissues, bones and joints, or lungs .
• Clindamycin: Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. It has a bacteriostatic activity against most gram-positive bacteria, including some methicillin-resistant S. hominis strains . It also has anti-inflammatory and immunomodulatory effects that may be beneficial for the treatment of S. hominis infections associated with inflammation or immune dysfunction. Clindamycin may be used in combination with other antibiotics for the treatment of refractory or severe S. hominis infections .
• Other antibiotics: Other antibiotics that may be used for the treatment of S. hominis infections include beta-lactams (such as penicillins, cephalosporins, or carbapenems), fluoroquinolones (such as ciprofloxacin or levofloxacin), rifampin, trimethoprim-sulfamethoxazole, or tigecycline . However, their use should be based on the susceptibility profile of the isolate and the clinical scenario.

Wound drainage

If the infection involves a skin lesion or an abscess, wound drainage may be necessary to remove pus and necrotic tissue and facilitate healing. Wound drainage can be performed by making a small incision into the lesion and applying gentle pressure to squeeze out the fluid.

Device removal

If the infection is related to a medical device implant, such as a catheter or a valve, device removal may be required to eradicate the infection and prevent complications. Device removal should be done as soon as possible after diagnosis and before starting antibiotic therapy .

Probiotics

Probiotics are live microorganisms that can confer health benefits to the host when administered in adequate amounts. Some probiotics, such as S. hominis A9, a bacterium isolated from healthy human skin, have been shown to have anti-staphylococcal activity and anti-inflammatory effects. S. hominis A9 can kill S. aureus on the skin of mice and inhibit the expression of a toxin from S. aureus that promotes inflammation. S. hominis A9 may be used as a topical therapy for S. hominis infections involving the skin, especially in patients with atopic dermatitis.

Because S. hominis is a multi-drug resistant species and is capable of forming elaborate biofilms, it is necessary to employ different resistant strategies to avoid such infections. The following are some preventive strategies that can be followed to avoid such infections:

• Clean and cover wounds. If you have a cut or other wound, wash it immediately with soap and water to prevent infection. Keep the wound clean and covered with a sterile, dry bandage until it’s fully healed .
• Wash your hands with soap and water regularly. This can help remove any bacteria from your skin and prevent the spread of infection to yourself or others.
• Avoid sharing personal items. Do not share towels, razors, clothing, or other items that may come into contact with your skin or body fluids. This can help prevent the transmission of bacteria from one person to another.
• Use aseptic techniques when handling medical devices. If you have a catheter, an artificial valve, or any other medical device implanted in your body, follow the instructions given by your health care provider on how to care for it. Use sterile gloves and equipment when inserting, removing, or changing the device. Clean the insertion site and catheter hubs regularly with antiseptic solutions .
• Coat biomaterials with antibacterial agents. If possible, use medical devices that are coated with substances that can prevent bacterial adhesion and biofilm formation. These substances may include silver, chlorhexidine, or antibiotics.
• Seek medical attention if you have signs of infection. If you notice any symptoms of staph infection, such as redness, swelling, pain, pus, fever, or chills, contact your health care provider as soon as possible. Early diagnosis and treatment can help prevent complications and reduce the risk of spreading the infection to others .

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