- Along with Morganella and Providencia, the genus Proteus is a member of the tribe Proteeae.
- The term “Proteus” relates to their pleomorphic feature, which is named after the Greek god Proteus, who could assume any form.
- With few exceptions, all members of the tribe Proteeae are Gram-negative, noncapsulated, pleomorphic, and motile bacilli.
- With the exception of certain Providencia strains, the majority of these bacteria produce the enzyme urease, which hydrolyzes urea into ammonia and carbon dioxide.
- They breakdown tyrosine, are MR positive and VP negative, and proliferate in the presence of KCN.
- They do not decarboxylate amino acids like arginine, lysine, or ornithine dehydrogenase.
- They neither ferment lactose nor dulcitol, nor use malonate.
- The production of the enzyme phenyl alanine deaminase, which converts phenyl alanine to phenyl pyruvic acid (PPA reaction), distinguishes Proteeae from other members of the Enterobacteriaceae family.
- The genus Proteus comprises four species: Proteus mirabilis, Proteus vulgaris, Proteus penneri, and Proteus myxofaciens. P. mirabilis is the most significant species, causing 90% of Proteus infections and being linked to urinary tract and wound infections acquired in the community.
- Typically, P. vulgaris and P. penneri are linked to hospital-acquired illnesses.
- They are separated from patients with chronic debilitating conditions and immunocompromised individuals.
Morphology of Proteus
Proteus demonstrates the following characteristics:
- Proteeae organisms are Gram-negative, noncapsulated, 1–3 0.6 m coccobacilli.
- They are organised singly, in pairs, and in brief chains.
- In young cultures, many of them create long, curved, filamentous shapes.
- With few exceptions, the majority of them are motile due to the presence of peritrichous flagella.
- They are covered in hair.
Culture of Proteus
Proteeae organisms are aerobic bacteria that thrive on common media like nutrient agar. On the medium, colonies of Proteus exude a putrefactive (or “fishy” or “seminal”) stench.
- P. mirabilis and P. vulgaris generally disperse or swarm over the medium’s surface.
- In subsequent waves, they spread across the plate’s surface to produce a thin, filmy layer in concentric rings. This is referred to as swarming.
- The precise mechanism responsible for Proteus species’ swarming behaviour is unknown.
- Proteus’ swarming is a problem when mixed growth on a solid media is produced with Proteus bacilli present alongside other bacteria.
- Consequently, there are a number of ways to prevent swarming, such as increasing the agar concentration in the medium from 1–2% to 6% and using chloral hydrate (1:500), sodium azide (1:500), alcohol (56%), sulfamide, surface active chemicals, or boric acid (1:1000).
- On MacConkey media, on which Proteus builds colourless, nonlactose-fermenting colonies, swarming does not occur.
- Due to the presence of bile salts in the MacConkey medium, swarming is inhibited.
Biochemical properties of Proteus
- Proteus species ferment glucose alone to produce acid.
- They are positive for urease and PPA.
- They do not ferment lactose, mannitol, mannose, inositol, adonitol, dulcitol, sorbitol, raffinose, and arabinose.
- They convert nitrate to nitrite without using malonate.
- They are incapable of decarboxylating amino acids such as lysine and arginine.
- Proteus species have varied hydrogen sulphide and indole producing responses. P. mirabilis is negative for indole, whereas P. vulgaris is positive.
Cell Wall Components and Antigenic Properties
Antigens O and H are present on the somatic and flagellar surfaces of motile Proteus strains. Somatic O antigens are heat-stable proteins that are resistant to 100 degrees Celsius of heating. Additionally, they are resistant to ethanol and diluted hydrochloric acid. P. mirabilis has 32 distinct O antigens, P. vulgaris has 22, while P. penneri and P. myxobacien each have five.
- The O antigen comprises components that are both alkali-labile and alkali-stable. The alkali-stable component is a polysaccharide and exhibits cross-reactivity with particular rickettsial antigens. Antigens shared with rickettsial antigens were first noted by Weil and Felix. They discovered that the sera of typhus fever patients agglutinated particular nonmotile strains of P. vulgaris known as “X strains.” This heterophilic agglutination by certain Proteus strains served as the basis for the Weil–Felix reaction, which is used to diagnose certain rickettsial illnesses. The Weil–Felix agglutination test employs the nonmotile Proteus strains OXl9 (P. vulgaris serotype O1), OX2 (P. vulgaris serotype O2), and OXK (P. mirabilis).
- Flagellar antigens are heat-labile, ethanol- and hydrochloric acid-sensitive proteins.
P. mirabilis and P. vulgaris have been divided into 54 O groups based on their O antigens. Depending on their flagellar or H antigens, these O groups are further split into a vast number of O types.
Pathogenesis and Immunity
Proteus possesses following virulence factors:
- Important virulence factors that allow P. mirabilis adhesion to host tissue locations, such as the urinary tract epithelium, are fimbriae or pili.
LPS or endotoxin
- This results in a series of inflammatory responses from the host and is the source of Gram-negative endotoxin-induced sepsis caused by Proteus species.
- Proteus organisms’ ability to manufacture urease is a crucial element in the pathophysiology of UTIs caused by Proteus species.
Hydrolysis of urea to ammonia renders urine alkaline, which provides Proteus with a favourable environment for survival. Consequently, the alkalization of urine precipitates organic and inorganic components, resulting in the development of stones in renal calculi. These stones are made of struvite (magnesium ammonium phosphate) and apatite (calcium carbonate).
Pathogenesis of UTI
- The pathogenesis of a Proteus infection is determined by the interaction between the bacteria and the host’s immune system.
- The adhesion of bacteria to host tissue, mediated by fimbriae, is the initial step in the progression of disease.
- Attachment of Proteus species to uroepithelial cells induces interleukin-6 and interleukin-8 production.
- Epithelial cells are also induced to undergo apoptosis and desquamation by Proteus.
- Infection of the urinary system is further promoted by the development of the enzyme urease and the bacteria’s motility.
- Urease converts urea to carbon dioxide and ammonia.
- The ammonia/ammonium buffer pair has a pH of 9.0, resulting in the excretion of ammonia-rich, strongly alkaline urine.
- The alkalinity of urine contributes to the formation of renal stones, which is commonly found in individuals with urinary tract infections caused by Proteus species.
Infrequently, Proteus spp. or other bacteria, including Enterobacter spp., Klebsiella spp., Serratia spp., and Acinetobacter spp., infect patients with multiple antibiotic treatments, urinary tract obstruction, or infection developing after catheterization or instrumentation. Proteus species are responsible for (a) urinary tract infections, (b) hospital-acquired infections, and (c) additional infections.
Urinary tract infections
- UTIs are the most prevalent clinical symptom of Proteus infections.
- Proteus is responsible for 1–2% of UTIs in healthy women and 5% of UTIs acquired in hospitals.
- It is responsible for 20–45% of catheterization-related UTIs.
- Patients with a urinary tract infection may exhibit urethritis, cystitis, prostatitis, or pyelonephritis. Chronic UTIs are associated with recurrent, persistent stones. Numerous magnesium ammonium phosphate crystals can be observed in the sediments of urine.
- Hospital-acquired infections are typically spread by attending physicians or other healthcare workers and are caused by the hospital staff’s breach of the closed sterile system.
- The Proteus genus is a significant cause of wound infections.
- Additionally, this species causes infection of the umbilical stump in newborns, which frequently results in sepsis neonatorum, bacteremia, and meningitis.
- Nonclostridial anaerobic myonecrosis, which affects subcutaneous tissue, fascia, and muscle, is also caused by Proteus spp.
- This disease typically coexists with other aerobic Gram-negative bacilli (such as E. coli, Klebsiella spp., or Enterobacter spp.) and anaerobes.
- Proteus organisms such as Pseudomonas can produce Gram-negative endotoxin-induced sepsis, which results in systemic inflammatory response syndrome with a 20–50% death risk.
Epidemiology of Proteus
- Worldwide, Proteus infections are prevalent.
- They are opportunistic bacteria that cause urinary tract infections and hospital-acquired illnesses.
- Proteus is widely distributed in nature as a saprophyte.
- They are frequently discovered in sewage, manure soil, human and animal wastes, and decaying animal products.
- Along with E. coli and Klebsiella species, Proteus species are the most frequent members of the normal human gut flora.
- They are also present on the skin’s moist places.
- Most frequently, they invade the skin and oral mucosa of hospital patients and hospital staff. The majority of patient infections originate from these reservoirs.
- Proteus species can be typed using (a), (b), (c), and (d) serotyping, phage typing, bacteriocin (proticin), and Dienes typing, respectively.
- Typically, 12 standard proticin-producing Proteus strains are used to type proticin, and the vast majority of Proteus strains are typeable using this procedure.
Laboratory Diagnosis of Proteus
- Urine is the preferred specimen for diagnosing UTIs.
- Urine is collected in the same manner as previously described for E. coli-related UTIs.
- Depending on the nature of infections, other specimens may be collected.
- These include pus from wound infections, blood from septicemia, cerebrospinal fluid from meningitis, etc.
- The definitive diagnosis is determined by the isolation of Proteus spp. from diverse clinical specimens through culture.
- Urine is cultured in the same manner as previously described for E. coli and other Gram-negative bacteria.
- Various biochemical tests and agglutination responses are used to identify pale, nonlactose-fermenting Proteus colonies on the MacConckey agar and those on the blood agar after an overnight incubation at 37°C.
- Blood, cerebrospinal fluid, and other specimens are also cultured based on the clinical diseases caused by Proteus.
Treatment of Proteus
- The selection of a particular antimicrobial agent is contingent upon the antibiotic susceptibility patterns of isolating strains.
- With the exception of tetracycline, P. mirabilis is susceptible to practically all antimicrobials.
- P. mirabilis is susceptible to ampicillin, broad-spectrum penicillins such as ticarcillin and piperacillin, first, second, and third generation cephalosporins, imipenem, and aztreonam.
- 10%–20% of strains develop resistance to ampicillin and first-generation cephalosporins, which is not a substantial problem.
- Rarely does resistance to extended-spectrum beta-lactams develop.
- P. vulgaris and P. penneri are sensitive to trimethoprim and sulfamethoxazole, quinolones, imipenem, aminoglycosides, and cephalosporins of the fourth generation.
- They are resistant to ampicillin and cephalosporins of the first generation.
- The resistance is mediated by an inducible chromosomal beta-lactamase that is activated in up to 30% of these strains.
Prevention and Control of Proteus
- Hand washing is the key to preventing the transfer of disease from one patient to another by medical workers.
- The ability of a vaccine generated from purified mannose-resistant/Proteus-like (MR/P) fimbriae proteins to prevent infection in experimental mice models is the subject of ongoing clinical investigation.
- The vaccine has not yet been tested on humans.