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Proteus infection

This page is about clinical aspects of the disease.  For microbiologic aspects of the causative organism(s), see Proteus.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords:

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Historical Perspective

Pathophysiology

Classification

Causes

Screening

Differential Diagnosis

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Primary Prevention

Secondary Prevention

Cost-effectiveness of Therapy

Future or Investigational Therapies

References

Historical Perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

Overview

Proteus infections were first described by Gustav Hauster, a German pathologist, in 1885. Hauster coined the term Proteus based on the organism’s ability to change shape from Homer’s Greek tale, the Odyssey.

Historical Perspective

  • Proteus infections were first described by Gustav Hauster, a German pathologist, in 1885.
  • Hauster coined the term Proteus based on the organism’s ability to change shape from Homer’s Greek tale, the Odyssey. Proteus refers to the “sea god” or “Poseidon’s herdsman of the seals”.[1]
  • Hauser also coined the terms P. vulgaris (i.e. the usual) and P. mirabilis (i.e. the marvelous or the unusual).

References

  1. Sellaturay SV, Nair R, Dickinson IK, Sriprasad S (2012). “Proteus: Mythology to modern times”. Indian J Urol. 28 (4): 388–91. doi:10.4103/0970-1591.105748. PMC 3579116. PMID 23450503.
Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Proteus is part of the normal human gastrointestinal flora and is usually associated with development of urinary tract infections (most common), pnuemonia, and local wound infections by self-contamination. Following self-contamination, Proteus accesses the urinary tract through the urethra and overproduces flagella (transforms from swimmer to swarmer) to ascend in a retrograde manner to the upper urinary tract. In the bladder, Proteus uses fimbriae and adhesins to bind to mucosal surfaces. To avoid host defenses, Proteus produces virulence factors, such as IgA-degrading protease, hemolysin, and urease. As urease is produced, urea is hydrolyzed to ammonia and carbon dioxide, resulting in the increase in the local pH of the urinary tract and precipitation of magnesium and calcium ions. As ions precipitate, strutive (magnesium ammonium phosphate) stones form and epxand, giving Proteus the capacity to sequester within the stone cavities and to protect itself against the host defenses and antimicrobial agents.

Pathophysiology

Colonization

  • Proteus is part of the normal human gastrointestinal flora and is usually associated with development of urinary tract infections (most common), pnuemonia, and local wound infections by self-contamination.
  • Following self-contamination, Proteus accesses the urinary tract through the urethra and uses flagella to ascend in a retrograde manner to the upper urinary tract.[1]
  • During the motility process, the production of flagella markedly increases, and the organism changes from a single-cell, rod-shaped form (swimmer) to a multi-cell, elongated-form (swarmer).[2][1]
  • In the bladder, Proteus uses fimbriae and adhesins to bind to mucosal surfaces:[1]
  • Mannose-resistant fimbriae (MRF)
  • P. mirabilis fimbriae (PMF)
  • Ambient temperature fimbiae
  • Non-agglutinating fimbiae
  • P-like pilus

Evasion of Host Defenses

  • There are four mechanisms by which Proteus can use to evade the host defenses:[1][2]
  • Production of an IgA-degrading protease which functions to cleave the secretory IgA.
  • Expression of flagellin to synthesize flagella that provides the characteristic swarming motility of Proteus.
  • Expression of the MR/P fimbriae
  • Production of urease (increases pH) to provide an adequate medium for bacterial growth. Urease production is also associated with stone formation in the kidneys and the bladder.[3]
Production of hemolysin, a cytotoxin involved in injury of host epithelial cells are known to cause damage to host epithelial cells. As mentioned above, urease can damage host epithelial cells through the formation of stones. Hemolysin damages cells

Formation of Stones / Staghorn Calculi

  • Proteus produces urease, which catalyzes the hydrolysis of urea tot ammonia and carbon dioxide.[4]
  • The ammonia results in an increase in the local pH of the urinary tract, resulting in the precipitation of magnesium and calcium ions and subsequent formation of struvite (composed of magnesium ammonioum phosphate) and carbonate hydroxyapatite stones.[4][5][3]
  • Proteus is able to sequester in the stone cavities and replicate while avoiding host defenses and therapeutic agents.[5]
  • As the infection persists or as the human host is re-infected, the existing stone expands and occasionally blocks the urinary tract completely. Large stones are referred to as Staghorn calculi, given their resemblance to the horns of a stag (adult male deer).

References

  1. 1.0 1.1 1.2 1.3 Schaffer JN, Pearson MM (2015). “Proteus mirabilis and Urinary Tract Infections”. Microbiol Spectr. 3 (5). doi:10.1128/microbiolspec.UTI-0017-2013. PMC 4638163. PMID 26542036.
  2. 2.0 2.1 Coker C, Poore CA, Li X, Mobley HL (2000). “Pathogenesis of Proteus mirabilis urinary tract infection”. Microbes Infect. 2 (12): 1497–505. PMID 11099936.
  3. 3.0 3.1 Griffith DP, Musher DM, Itin C (1976). “Urease. The primary cause of infection-induced urinary stones”. Invest Urol. 13 (5): 346–50. PMID 815197.
  4. 4.0 4.1 Mobley HL, Island MD, Hausinger RP (1995). “Molecular biology of microbial ureases”. Microbiol Rev. 59 (3): 451–80. PMC 239369. PMID 7565414.
  5. 5.0 5.1 Dumanski AJ, Hedelin H, Edin-Liljegren A, Beauchemin D, McLean RJ (1994). “Unique ability of the Proteus mirabilis capsule to enhance mineral growth in infectious urinary calculi”. Infect Immun. 62 (7): 2998–3003. PMC 302911. PMID 8005688.
Classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Proteus species are classified into four main serogroups: P. vulgaris, P. mirabilis, P. penneri, P. rettgeri, and P. morganii.

Classification

Proteus species are classified into four main serogroups:

  • P. mirabilis
  • P. vulgaris
  • P. penneri
  • P. rettgeri
  • P. morganii

References

Causes
This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Proteus infection.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Proteus is a urease-producing, motile, nitrite-reducing, hydrogen sulfide-producing, catalase-positive, facultatively anaerobic, Gram-negative bacillus. It can be found in soil, water, and fecal matter. It inhabits the intestinal tracts of humans and animals, and is considered an opportunistic pathogen of humans. Transmission to the human host (usually urinary tract) typically occurs via self-contamination.

Taxonomy

Kingdom: Bacteria; Phylum: Proteobacteria; Class: Gamma proteobacteria; Order: Enterobacteriales; Family: Enterobacteria; Genus: Proteus; Species: Proteus mirabilis

Genome

  • Proteus contains more than 3,658 coding sequences with 7 rRNA loci.[1]
  • Total genome length is 4.063 Mb (28.8% GC content).[1]
  • Proteus contains a single plasmid that contains 26,298 nucleotides.[1]

Microbiological Characteristics

  • Proteus is a urease-producing, motile, nitrite-reducing, hydrogen sulfide-producing, catalase-positive, facultatively anaerobic, Gram-negative bacillus.
  • It grows optimally at 40 °C (104 °F).
  • It produces hydrogen sulfide gas, and forms clear films on growth media. It is motile, possessing peritrichous flagella, and is known for its swarming ability. It is commonly found in the intestinal tracts of humans. P. mirabilis is not pathogenic in guinea pigs or chickens.
  • Characteristically, Proteus can inhibit the growth of other strains in culture media, resulting in a macroscopically visible line (Dienes line) of reduced bacterial growth where two swarming strains intersect.
  • The following table summarizes the microbiological characteristics of Proteus:
Test Result
Indole Negative
Nitrate reductase Positive (no formation of gas bubbles)
Methyl red Positive
Voges-Proskauer Negative (may be positive)
Catalase Positive
Cytochrome oxidase Negative
Phenylalanine deaminase Positive
Tryptophan Negative
Urea (Harnstoff test) Positive
Casein Negative
Starch Negative
Hydrogen sulfide Positive
Citrate agar Negative
Ornithine decarboxylase Positive
Lysine decarboxylase Negative
Glucose fermentation Positive
Amygdalin fermentation Positive
Mannitol fermentation Negative
Lactose fermentation Negative

Natural Reservoir

  • Proteus can be found in soil, water, and fecal matter.
  • It inhabits the intestinal tracts of humans and animals, and is considered an opportunistic pathogen of humans.

Transmission

  • Proteus is usually transmitted to the human host by self-contamination (e.g. fecal material from gastrointestinal tract to genitourinary tract).

References

  1. 1.0 1.1 1.2 Pearson MM, Sebaihia M, Churcher C, Quail MA, Seshasayee AS, Luscombe NM; et al. (2008). “Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility”. J Bacteriol. 190 (11): 4027–37. doi:10.1128/JB.01981-07. PMC 2395036. PMID 18375554.
Differentiating Proteus infection from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hari Krishnan Nair, M.D.

Overview

Proteus infection must be differentiated from other types of infectious diseases that cause acute urinary tract infection, pneumonia and local wound infections such as Escherichia coli, Klebsiella and Pseudomonas.

Epidemiology and Demographics

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hari Krishnan Nair, M.D.

Overview

Proteus infections occur worldwide, and are generally considered pathogenic for young individuals and opportunistic pathogens for the elderly. The elderly, particularly those who are on long-term catheterization or under frequent antibiotic therapy, prepubescent males and females, and individuals with structural abnormalities of the urinary tract are more susceptible to infection.

Risk Factors
Natural History, Complications and Prognosis
Diagnosis

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Other Diagnostic Studies

Treatment

Treatment

Medical Therapy | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

Case Studies

Case Studies

Case #1

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