The Genus Staphylococcus

Chapter 4 The Genus Staphylococcus



THE GENUS STAPHYLOCOCCUS


The gram-positive aerobic cocci are conve-niently divided into two groups based on cata-lase production. The family Micrococcaceae (genera Micrococcus, Staphylococcus, and Rothia [Stomatococcus]) are catalase positive, whereas the genera Streptococcus, Enterococcus, Eremococcus, Gemella, Globicatella, Helcococcus, and Vagococcus are catalase negative.


Staphylococci are the most commonly isolated Micrococcaceae from veterinary clinical specimens. They occur in pairs, in grapelike clusters, or singly, and colonies are generally white to off-white, with smooth surfaces and butyrous consistency; many strains of Staphylococcus aureus have a golden pigment from which the organism derives its name. Members of the genus Staphylococcus can usually be differentiated from micrococci based on cell morphology (the latter form tetrads and cells tend to be larger than those of the staphylococci) and pigment production on solid media. Rothia (Stomatococcus) species are found infrequently in veterinary specimens, and a weak catalase reaction, ovoid cell shape, and sticky colonies are useful phenotypic features (Table 4-1). Rothia species are further distinguished from other members of the Micrococcaceae bythe low G+C content of its DNA (30%-38%), the presence of teichoic acid in their cell walls, andthe ability to tolerate high levels of NaCl (15% to saturated).



There are 32 recognized species of staphylococci (Table 4-2), 13 of which are indigenous to humans, with the remainder associated with various nonprimate animals. They are aerobic or facultatively anaerobic, and are capable of generating energy by respiratory and fermentative pathways. Staphylococci are nutritionally fastidious, with complex nitrogen requirements; most species require several amino acids, vitamins (thiamine and niacin), and uracil (to grow anaerobically).In complex, nutritionally complete media, the organism has a generation time of approximately 20 minutes.


TABLE 4-2 Species of Staphylococcus Important in Veterinary Medicine






















































Staphylococcus Species Veterinary Importance
S. aureus Wound infections in all animals; mastitis, skin infections; joint infections, especially in chickens; diarrhea in pet birds; vaginal infections in dogs and horses
S. aureus ssp. anaerobius Isolated occasionally from ovine caseous lymphadenitis
S. epidermidis Opportunistic pathogen; bovine mastitis, skin abscesses in other animals
S. warneri Septicemia in lovebirds
S. saprophyticus Possible opportunist in urinary tract infections
S. kloosii Normal skin and mucous membrane flora in squirrels and opossums
S. intermedius Skin and ear infections in dogs, occasional bovine mastitis; isolated occasionally from birds and horses
S. hyicus Skin infections, arthritis in pigs; skin, milk of cattle; avian arthritis
S. chromogenes Bovine milk, skin of pigs and cattle; normal skin and mucous membrane flora in cattle
S. sciuri Normal skin and mucous membrane flora in squirrels
S. lentus Normal skin and mucous membrane flora in sheep and goats
S. gallinarum Normal skin and mucous membrane flora in turkeys
S. caprae Normal skin and mucous membrane flora in goats
S. equorum, arlettae Normal skin and mucous membrane flora in horses
S. felis Otitis externa, cystitis, abscesses and wounds in cats only
S. auricularis, S. capitis, S. carnosus, S. caseolyticus, S. cohnii, S. haemolyticus, S. hominis, S. lugdenensis, S. muscae, S. pasteuri, S. piscifermentans, S. saccharolyticus, S. schlieferi, S. simulans, S. vitulus, S. xylosus None known

The staphylococcal cell wall is composed primarily of peptidoglycan complexed with teichoic acid, and is resistant to lysozyme digestion by virtue of O-acetylation of muramic acid residues. In S. aureus the teichoic acid backbone is ribitol based, whereas in Staphylococcus epidermidis it is glycerol based. In other species, glycerol teichoic acids are more common than their ribitol counter-parts.


Eleven capsular polysaccharide serotypes have been described for S. aureus, and the most common in clinical isolates are types 5 and 8. The main capsular components are N-acetylaminouronic acids and N-acetylfucosamine. The genes for capsule production are in a single chromosomal operon.


The genome of S. aureus is circular and consists of approximately 2.8 Mb. In addition to the normal complement of housekeeping genes, the chromosome contains many accessory genetic elements that are not necessary for growth under laboratory conditions. The genes and genomic organization are so strikingly similar to those of Bacillus subtilis that some have referred to S. aureus as a morphologically degenerate Bacillus sp.


Staphylococci are also equipped with copious plasmids, ranging in size up to approximately50 kb pairs. Most of the smaller plasmids encode resistance to one or more antibiotics, and the majority of large plasmids encode resistance to penicillin or heavy metals; a few have conjugative functions by which they can mobilize themselves and other plasmids. Dogma holds that plasmids are exchanged among staphylococci, streptococci, and bacilli, accounting for the presence of the same or similar plasmids in each genus.


Staphylococcal bacteriophages were among the first demonstrated, and this has led to the establishment of a bacteriophage typing method for epidemiologic studies. Most pathogenic strains belong to phage groups II and III, but all arecapable of causing disease.


Phage typing can be complicated by the fact that virtually all strains of S. aureus are lysogenized by one or more temperate bacteriophages. Phage insertion can alter the phenotype of a strain by introduction of genes and by integration at specific attachment sites within chromosomal genes; thus both negative conversion (inactivation of genes, such as those for lipase and β-toxin) and positive conversion (introduction of genes such as those for enterotoxin A and staphylokinase) are common. Transduction to penicillin resistance was reported more than 40 years ago. Most staphylococcal bacteriophages are now known to be capable of transferring approximately 40 kb of DNA.



Diseases and Pathogenesis


Staphylococci may be transient contaminants, short-term replicating residents, or long-termcolonizers of the skin of mammals. Most that cause infection do so when the skin or mucous membranes are compromised in some way. Infections by S. aureus often begin at some breach in the epithelial barrier, whether keratinized, mucosal, or conjunctival, and establishment of infection is facilitated by foreign bodies, such as catheters, sutures, or even debris.


Virulence of staphylococci for domestic animals is almost always multifactorial, but interaction with animal hosts usually includes a few common steps. They produce microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), which comprise the main adhesins of the organism and include collagen-binding protein, fibronectin-binding proteins, fibrinogen-binding protein, elastin-binding protein, clumping factor, and the matrix adhesin factor. As many as 12 other surface proteins may contain membrane anchor domains and potentially qualify as MSCRAMMs. Roles in virulence have been postulated but not confirmed for infections of domestic animals.


Staphylococci are killed by neutrophils, so many of their virulence attributes are focused upon avoiding phagocytosis or intracellular killing. This is mediated in large part by production of capsules and protein A. Capsules, produced in 12 immunotypes, are antiphagocytic and those of type 1 are associated with enhanced virulence. Those strains not producing a type 1 macrocapsule may produce a polysaccharide microcapsule (for example, strains from mastitis); nonencapsulated strains are substantially more susceptible to phagocytosis and, in bovine mastitis and other in vivo models, less virulent. Protein A, which is found on the surface of the vast majority of strains of S. aureus, binds immunoglobulins by their Fc portion, limiting the degree of opsonization for phagocytosis. Mutants have reduced virulence in some in vivo systems. In a similar vein, teichoic acids and peptidoglycan fragments may serve as decomplementation antigens, exhausting in free solution the supply of complement components that would ordinarily be available for bacterial surface deposition (and thus opsonization). There are clearly two sides to this bacterial approach in host interaction: peptidoglycan interaction with host factors leads to complement activation (by classical or alternate pathways) and neutrophil chemotaxis.


Coagulase activates thrombin, with subsequent conversion of fibrinogen to fibrin. Some staphylococci produce coagulase (S. aureus, Staphylococcus intermedius, Staphylococcus schlieferi ssp. coagulans, and Staphylococcus delphini), while mostdo not; coagulase production by Staphylococcus hyicus is variable. The dogma that coagulaseproduction distinguished pathogenic from non-pathogenic species held until coagulase-negative staphylococci (CoNS) were recognized as a major cause of wound infections and infections associated with foreign bodies including catheters, prosthetic heart valves, joint prostheses, and pacemaker electrodes; thus coagulase is no longer an exclusive indicator of pathogenicity. Coagulase mutants and parent strains are of equivalentvirulence in various animal models of infection; nonetheless, some speculate that the enzyme participates in the infectious process by walling off the site of infection (limiting leukocyte infiltration and protecting the organisms against phagocytosis) or cloaking staphylococci in host proteins and preventing recognition as nonself.


Intracellular survival and spread are mediated in large part by production of toxins. Membrane-active toxins, some of which are enzymes, pro-tect the organism against the host response and provide access to host-derived nutrients. Many of the approximately 30 extracellular proteins produced by S. aureus are plasmid encoded, providing an armada of potential virulence factors that varies from strain to strain (Table 4-3). A single bacterial product is rarely of overriding importance in development of disease. Alpha toxin subunits bind to cell membranes, oligomerize, and form pores, leading to necrosis. Prostaglandins and other inflammatory mediators are released from some target cells, and macrophage function is compromised. Systemic effects of alpha toxin are most pronounced on cardiac and central nervous system tissue. Most bovine isolates of S. aureus produce β-toxin, a sphingomyelinase that lyses susceptible cells by enzymatic degradation of phospholipids in the outer leaflet of the membrane. Its role in pathogenesis is less clearly understood, but it augments staphylococcal growth in vivo. Hyaluronidase is a putative virulence attribute that may contribute to spread of the organism in the host.


TABLE 4-3 Virulence Factors of Staphylococcus aureus










































Virulence Factor Effects
Capsule Inhibits phagocytosis; promotes adherence
Peptidoglycan Leukocyte chemoattractant; decomplementation
Teichoic acid Fibronectin binding
Protein A Immunoglobulin binding
Toxins (α, β, others) Antiphagocytic; cytotoxic
Exfoliative toxins Serine proteases; split cellular bridges in stratum granulosum
Enterotoxins Superantigens; nauseogenic, diarrheagenic
Toxic shock syndrome toxin Superantigen; endothelial damage
Coagulase Converts fibrinogen to fibrin
Hyaluronidase Hydrolyzes hyaluronic acid in connective tissue
Lipase Hydrolyzes lipids
Nuclease Hydrolyzes deoxyribonucleic acid (DNA)

Staphylococcus aureus causes suppurative infections and septicemia (Figure 4-1) in all species, and a few examples are illustrative. Arthropod bite wounds in lambs and other animals may become infected, and these animals may also develop lameness and bacteremia. Abscesses form in kidney, liver, joints, and brain, and death is rapid. The organism may also be associated with ovine periorbital eczema.


< div class='tao-gold-member'>

Stay updated, free articles. Join our Telegram channel

Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on The Genus Staphylococcus

Full access? Get Clinical Tree

Get Clinical Tree app for offline access