''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a

spirochaete A spirochaete () or spirochete is a member of the phylum Spirochaetota (), (synonym Spirochaetes) which contains distinctive diderm (double-membrane) gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or s ...

bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

with various subspecies that cause the diseases

syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...

bejel Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the ''endemicum'' subspecies of the spirochete ''Treponema pallidum''. Bejel is one of the "endemic treponematoses" (endemic infections caused by spiral-shaped ...

(also known as endemic syphilis), and

yaws Yaws is a tropical infection of the skin, bones, and joints caused by the spirochete bacterium ''Treponema pallidum pertenue''. The disease begins with a round, hard swelling of the skin, in diameter. The center may break open and form an ulce ...

. It is transmitted only among humans. It is a helically coiled microorganism usually 6–15 μm long and 0.1–0.2 μm wide. ''T. pallidum'''s lack of either a

tricarboxylic acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine tri ...

results in minimal metabolic activity. The treponemes have a cytoplasmic and an outer membrane. Using

light microscopy Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of micr ...

, treponemes are visible only by using dark field illumination. ''Treponema pallidum'' consists of three subspecies, ''T. p. pallidum, T. p. endemicum,'' and ''T. p. pertenue,'' each of which has a distinct associated disease.

Subspecies

Three

subspecies In biological classification, subspecies is a rank below species, used for populations that live in different areas and vary in size, shape, or other physical characteristics (morphology), but that can successfully interbreed. Not all species ...

of ''T. pallidum'' are known: * ''Treponema pallidum pallidum'', which causes syphilis * ''T. p. endemicum'', which causes bejel or endemic syphilis * ''T. p. pertenue'', which causes yaws The three subspecies causing

, and

are morphologically and serologically indistinguishable. These bacteria were originally classified as members of separate species, but DNA hybridization analysis indicates they are members of the same species. ''Treponema carateum'', the cause of pinta, remains a separate species because no isolate is available for DNA analysis. Disease transmittance in subspecies ''T. p. endemicum'' and ''T. p. pertenue'' is considered non-venereal. ''T. p. pallidum'' is the most invasive pathogenic subspecies while ''T. p. carateum'' is the least invasive of the subspecies. ''T. p. endemicum'' and ''T. p. pertenue'' are intermediately invasive.

Microbiology

Ultrastructure

''Treponema pallidum'' is a helically shaped bacterium with high mobility consisting of an outer membrane,

peptidoglycan layer Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...

, inner membrane, protoplasmic cylinder, and

periplasmic space The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the ''periplasmic space'' in gram-negative bacteria. Using cryo-electron microscopy it has been found tha ...

. It is often described as

Gram negative The gram (originally gramme; SI unit symbol g) is a unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram. Originally defined as of 1795 as "the absolute weight of a volume of pure water equal to th ...

, but its outer membrane lacks

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

, which is found in the outer membrane of other Gram-negative bacteria. It has an endoflagellum (periplasmic flagellum) consisting of four main

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

s, a core structure, and a sheath. The flagellum is located within the periplasmic space and wraps around the protoplasmic cylinder. ''T. pallidum'''s outer membrane has the most contact with host cells and contains few

transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...

s, limiting antigenicity while its cytoplasmic membrane is covered in lipoproteins. The outer membrane's treponemal ligands main function is attachment to host cells, with functional and antigenic relatedness between ligands. The genus ''Treponema'' has ribbons of cytoskeletal cytoplasmic filaments that run the length of the cell just underneath the cytoplasmic membrane. They are composed of the intermediate filament-like protein CfpA (cytoplasmic filament protein A). Although the filaments may be involved in chromosome structure and segregation or cell division, their precise function is unknown.

Outer Membrane Proteins

Treponemal outer membrane proteins are key factors for its pathogenesis, persistence and immune evasion strategies.

= TP0326

= TP0326 is an ortholog of BamA. BamA apparatus will insert newly synthetised and exported outer membrane proteins into the outer membrane

= Treponema repeat family of proteins

= Treponema repeat family of proteins, Tpr for short, are proteins expressed during the infection process. Tprs are formed by a conserved N-terminal domain, an amino-terminal stretch of about 50 aminoacids, a central variable region and a conserved C-terminal domain .There are many different types of tpr: tprA, tprB, tprC, tprD, tprE…However, variability of tprK is the most relevant due to the immune scape characteristics it allows. Antigen variation in TprK is regulated by gene conversion. In this way, fragments of the seven variable regions (V1–V7) present in tprK and the 53 donor sites of tprD can be combined to produce new structured sequences. TprK antigen variation can help ''Treponema pallidum'' to evade a strong host immune reaction and it can also allow the reinfection of individuals. This is possible because the newly structured proteins can avoid antibody specific recognition. In order to introduce more phenotypic diversity, ''Treponema pallidum'' may undergo phase variation. This process will mainly happen in tprF, tprI, tprG, tprJ, tprL and it consists of a reversible expansion or contraction of polymeric repeats. These size variations can help the bacterium to quickly adapt to its microenvironment, dodge immune response or even increase affinity to host.

Culture

Successful long-term cultivation of ''T. pallidum'' subspecies ''pallidum'' in a tissue culture system has been reported in 2018. However, because ''T. pallidum'' cannot be grown in a pure culture, it does not satisfy

Koch's Postulates Koch's postulates ( )"Koch"
''

This sequencing is significant due to ''T. pallidum'' not being capable of growing in a pure culture, meaning that this sequencing played an important role in understanding the microbe's functions. It revealed that ''T. pallidum'' relies on its host for many molecules provided by biosynthetic pathways, and that it is missing genes responsible for encoding key enzymes in oxidative phosphorylation and the tricarboxylic acid cycle. It was found that this is due to 5% of ''T. pallidum'''s genes coding for transport genes. The recent sequencing of the genomes of several spirochetes permits a thorough analysis of the similarities and differences within this bacterial phylum and within the species. ''T. p. pallidum'' has one of the smallest bacterial genomes at 1.14 million base pairs, and has limited metabolic capabilities, reflecting its adaptation through genome reduction to the rich environment of mammalian tissue. The shape of ''T. pallidum'' is flat and wavy. In order to avoid antibodies attacking, the cell has few proteins exposed on the outer membrane sheath. Its chromosome of about 1000 kilo base pairs is circular with a 52.8% G + C average. Sequencing has revealed a bundle of twelve proteins and some putative hemolysins are potential virulence factors of ''T. pallidum.'' 92.9% of DNA was determined to be

ORF ORF or Orf may refer to: * Norfolk International Airport, IATA airport code ORF * Observer Research Foundation, an Indian research institute * One Race Films, a film production company founded by Vin Diesel * Open reading frame, a portion of the ...

's, 55% of which had predicted biological functions.

Clinical significance

The clinical features of syphilis, yaws, and bejel occur in multiple stages that affect the skin. The skin lesions observed in the early stage last for weeks or months. The skin lesions are highly infectious, and the spirochetes in the lesions are transmitted by direct contact. The lesions regress as the immune response develops against ''T. pallidum''. The latent stage that results lasts a lifetime in many cases. In a minority of cases, the disease exits latency and enters a tertiary phase, in which destructive lesions of skin, bone, and cartilage ensue. Unlike yaws and bejels, syphilis in its tertiary stage often affects the heart, eyes, and nervous system as well.

Syphilis

''Treponema pallidum pallidum'' is a motile spirochaete that is generally acquired by close

sexual contact Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their Human sexuality, sexuality. People engage in a variety of sexual acts, ranging from activities done alone (e.g. ...

, entering the host via breaches in squamous or columnar

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

. The organism can also be transmitted to a fetus by

transplacental {{Short pages monitor