Proteus mirabilis - mucosal-immunology-lab/bacterial-database GitHub Wiki
| Bacterial Information | Value |
|---|---|
| Taxonomy level | Species |
| NCBI Taxonomy ID | 584 |
| Phylum | Proteobacteria |
| Family | Morganellaceae |
| Genus | Proteus |
| Gram stain | Gram-negative |
| Oxygen requirements | Facultative anaerobic |
| Spore-forming | No |
| Motile | Yes |
| Image |  |
Proteus mirabilis are Gram-negative, facultatively anaerobic, rod-shaped bacterium that is widely distributed in soil and water. It is responsible for 90% of Proteus infections in humans, and is most frequently associated with infections of the urinary tract, especially in complicated or catheter-associated urinary tract infections. Proteus species can also cause wound infections, sepsis, and pneumonia, mostly in hospitalised patients.
P. mirabilis can migrate across the surface of solid media or devices using a type of cooperative group motility known as swarming. It also produces high levels of urease (which hydrolyses urea to ammonia), making urine more alkaline – if left untreated, this can lead to the formation of crystals of struvite, calcium carbonate, and apatite, which can result in kidney stones.
Proteus mirabilis can be found in human and animal gastrointestinal tracts, skin, oral mucosa, and faeces. It can also be found in soil, water, and plants.
Proteus mirabilis has been shown to be increased in faecal samples and colonic tissue of Crohn's disease patients compared to healthy controls. Increased Fusobacterium and decreased Faecalibacterium were seen in patients with high Proteus abundance, along with decreased alpha diversity (by both Shannon and Chao indices) (Zhang 2020).
Mice gavaged with P. mirabilis showed more severe colonic inflammation – higher histopathology scores, colon length was decreased, spleen weight was increased, and myeloperoxidase activity was increased (Zhang 2020). P. mirabilis was also found to be highly adherent to enterocytes, and highly invasive.
NOD-like receptor, JAK-STAT, and MAPK signalling pathways were typically enriched by colonic cell lines (INT407 and NCM460) in response to P. mirabilis. Further, NF-κB activation and TNFα expression were enhanced. IL-18 and IL-1α secretion were significantly increased. IL-18 has been shown to contribute to breakdown of the mucosal barrier, and was shown here alongside decreased Claudin-3 (a tight junction protein) in P. mirabilis-inoculated NCM460 cells.
A number of gamma-Proteobacteria – notably the original Enterobacteriaceae family prior to its division (Adeolu 2016) – have been identified as commonly and markedly increased in the colon of patients with Parkinson's disease (PD) (Scheperjans 2015)(Garrett 2010)(Bloom 2011)(Unger 2016).
In a mouse model of PD (induced by MPTP, MPTP/probenecid, or 6-ODHA), the numbers of P. mirabilis (via solid media culture) significantly increased, while Escherichia and Klebsiella abundance remained unaltered – in the MPTP model, the colony forming units (CFU) per gram increased to almost 50 CFU/g from less than 10 CFU/g in the controls (Choi 2018).
Administration of P. mirabilis (2 x 108 CFU/0.2 mL daily per mouse) at the pre-motor phase of PD exacerbated striatal dopaminergic neuronal damage, and induced motor deficits (Choi 2018). Further, 5 days of treatment with P. mirabilis alone (without drug induction of PD) impaired motor function, while not impairing memory function. The distance travelled in an open field test was significantly reduced at both 8 and 16 days post-administration, although appeared to be potentially recovering.
At 8 and 16 days post-administration with P. mirabilis, there was severe damage to dopaminergic neurons in both the substantia nigra (part of the basal ganglia involved in movement amongst other roles) and the striatum, while the hippocampal and cortical neurons were unaffected, suggesting that P. mirabilis selectively damages dopaminergic neurons (Choi 2018).
P. mirabilis produces LPS, and high levels were observed by day 16 post-administration in both the faeces and serum (Choi 2018). This coincided with reduced protein levels of occludin (a colonic tight junction protein), alongside increased levels of inflammatory cytokine TNFα in the colon and colonic expression of TLR4 (an LPS binding receptor). This points towards P. mirabilis-derived LPS causing colonic pathologies including epithelial barrier disruption and inflammation.
- Intra-rectal injection of purified P. mirabilis LPS induced activation of microglia in the nigrostriatal regions of the brain, but not the hippocampus or cortex.
Concurrent upregulation of α-synuclein has been reported in enteric neurons and dopaminergic neurons (Gold 2013)(Natale 2011), and α-synuclein from enteric neurons can move into the substantia nigra via the vagus nerve in animal models (Holmqvist 2014)(Pan-Montojo 2012). Aggregation of α-synuclein is immunoreactive, and can cause neuroinflammation and dopaminergic neuronal cell death.
- At day 16 post-administration of P. mirabilis, there was significant increase in α-synuclein filaments (an aggregated form) in the distal colon, and increased immunoreactivity of α-synuclein filaments compared to controls in the substantia nigra and striatrum regions. It is likely that α-synuclein in the brain (at least somewhat) originated in the colon, as P. mirabilis treatment in vagotomised mice did not induce aggregation in the substantia nigra, while P. mirabilis-only treatment increased levels of aggregated α-synuclein.
Adapted from (Choi 2018)
The urease activity of P. mirabilis catalyses the hydrolysis of urea to ammonia (NH3), which makes urine more alkaline. This increased alkalinity can lead to crystalisation of struvite, calcium carbonate, and apatite, which can result in kidney stones and crystalline deposits on catheters (Norsworthy 2016)(Armbruster 2018).
P. mirabilis colonisation of a catheter can occur within 15 minutes post-inoculation, and as the adherent bacteria grow and divide into microcolonies, the pH rises, which leads to formation of crystals and further facilitation of bacterial adherence to the catheter (Norsworthy 2016).
P. mirabilis is strongly indicated in the formation of bacterial infection-induced kidney stone formation – Proteus species have been isolated in 70% of these cases (Prywer 2017).
- Transurethral inoculation of mice with a wild-type P. mirabilis strain resulted in formation of stones in 31% (12/39) of mice by 1 week, and 40% (8/20) by 2 weeks – no stone formation was observed when mice when inoculated with a urease-negative P. mirabilis strain (0/38) (Johnson 1993).
- P. mirabilis can be found within these stones, which could lead to reinfection after antibiotic treatment.