Proteus mirabilis: Isolating a Cause of Kidney Stones

The incidence of kidney stones in the United States is as high as 11% among men and 6% among women.¹ This translates into a 1-in-11 risk nationwide, with white men being at greater risk than any other cohort. However, for those patients with high-risk medical issues, such as metabolic syndrome, chronic indwelling urinary catheters, frequent catheterization, and/or recurrent urinary tract infections (UTIs), kidney stones are even more common.² Often, the cause of the stones in at-risk patients is an infection. The most frequent source of UTIs is Escherichia coli, but more complicated infections are often caused by Proteus mirabilis.³ Seventy percent of the stones resulting from UTIs are attributed to P mirabilis.⁴

In 2008, a group of microbiology researchers led by Melanie Pearson, PhD, were able to isolate the genome sequence of P mirabilis.⁵Proteus is a gram-negative enteric bacterium that is often found in complicated UTIs. Proteus is more common among patients with the aforementioned high-risk medical issues and is a particularly common cause of UTIs in the nursing home population (particularly in residents with indwelling catheters).³ It is also a potential cause of kidney stones.

While calcium stones are the most common type of stones,¹ infections, though uncommon, are a secondary source. Stones resulting from infection are imminently treatable; the difficulty is in isolating the source of the infection. Proteus is a particularly toxic, difficult-to treat bacterium that can become resistant to antibiotics.³Proteus produces the enzyme urease, which can reduce the acidity of the urine, allowing stones to form. Once stone formation begins, bacteria can sequester within the stone, making them less susceptible to antibiotic treatment.

Proteus often seems to occur randomly. It has been found as a cause of kidney stones, for example, in a patient who four months earlier underwent transurethral resection of the prostate.⁷Proteus has been reported in a nursing home patient with dementia but no known risk factors.⁸Proteus can cause a pyelonephritis to coalesce into a stone; this complicates what is already an insult to the urinary tract and makes treatment all the more complicated.⁹

Pearson’s group from the University of Michigan has spent the past 10 years sequencing the Proteus bacterium in order to try to gain a foothold in the fight against the infection and the kidney stones it can produce. In 2014 they published their findings on the fimbriae of the Proteus organism.¹⁰ Fimbriae are small pili, or adherence factors, found on the surface of a bacterium (more often on gram-negative bacteria than on gram-positive bacteria), which allow the bacteria to attach to urinary tract tissue and prevent them from being easily dislodged.¹¹ Pearson’s group also found that the fimbriae of the Proteus bacterium are more numerous than those of other bacteria, allowing Proteus to more easily attach to tissue than, say, Salmonella enterica.⁵ Thus, Proteus is more likely than other uropathogenic agents to cause a kidney stone, in part because of the “stickiness” of its many fimbriae.

While stones with an infectious cause are less common than others, they are a danger to our most fragile patients. Thus, when an infectious kidney stone forms, it will require aggressive treatment and a hard-hitting plan to minimize recurrence. Proteus is an especially virulent organism that will require all our resources to overcome it.

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-165.

2. National Kidney Foundation. Diet and kidney stones. kidney.org/atoz/content/diet.cfm. Accessed October 1, 2104.

3. University of Michigan Health System. Bacterium that causes kidney stones and complicated urinary tract infections gives up its genetic secrets (2006). ScienceDaily. sciencedaily.com/releases/2006/05/060524125023.htm. Accessed October 1, 2014.

4. Torzewska A, Budzyńska A, Białczak-Kokot M, Różalski A. In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development. Microb Pathog. 2014;71-72:25-31.

5. Pearson MM, Sebaihia M, Churcher C, et al. Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol. 2008;190(11):4027-4037.

6. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

7. Rowe CM, Ghei M, Adamska E. Moans, groans and renal stones: an interesting case of abdominal pain. BMJ Case Rep. 2013 Nov 4.

8. Chew R, Thomas S, Mantha ML, et al. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81(8):802.

9. Shields J, Maxwell AP. Acute pyelonephritis can have serious complications. Practitioner. 2010;254(1728):19, 21, 23-24.

10. Kuan L, Schaffer JN, Zouzias CD, Pearson MM. Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation. J Med Microbiol. 2014;63(pt 7):911-922.

11. Proft T, Baker EN. Pili in Gram-negative and Gram-positive bacteria: structure, assembly and their role in disease. Cell Mol Life Sci. 2009;66(4):613-635.

The incidence of kidney stones in the United States is as high as 11% among men and 6% among women.¹ This translates into a 1-in-11 risk nationwide, with white men being at greater risk than any other cohort. However, for those patients with high-risk medical issues, such as metabolic syndrome, chronic indwelling urinary catheters, frequent catheterization, and/or recurrent urinary tract infections (UTIs), kidney stones are even more common.² Often, the cause of the stones in at-risk patients is an infection. The most frequent source of UTIs is Escherichia coli, but more complicated infections are often caused by Proteus mirabilis.³ Seventy percent of the stones resulting from UTIs are attributed to P mirabilis.⁴

In 2008, a group of microbiology researchers led by Melanie Pearson, PhD, were able to isolate the genome sequence of P mirabilis.⁵Proteus is a gram-negative enteric bacterium that is often found in complicated UTIs. Proteus is more common among patients with the aforementioned high-risk medical issues and is a particularly common cause of UTIs in the nursing home population (particularly in residents with indwelling catheters).³ It is also a potential cause of kidney stones.

While calcium stones are the most common type of stones,¹ infections, though uncommon, are a secondary source. Stones resulting from infection are imminently treatable; the difficulty is in isolating the source of the infection. Proteus is a particularly toxic, difficult-to treat bacterium that can become resistant to antibiotics.³Proteus produces the enzyme urease, which can reduce the acidity of the urine, allowing stones to form. Once stone formation begins, bacteria can sequester within the stone, making them less susceptible to antibiotic treatment.

Proteus often seems to occur randomly. It has been found as a cause of kidney stones, for example, in a patient who four months earlier underwent transurethral resection of the prostate.⁷Proteus has been reported in a nursing home patient with dementia but no known risk factors.⁸Proteus can cause a pyelonephritis to coalesce into a stone; this complicates what is already an insult to the urinary tract and makes treatment all the more complicated.⁹

Pearson’s group from the University of Michigan has spent the past 10 years sequencing the Proteus bacterium in order to try to gain a foothold in the fight against the infection and the kidney stones it can produce. In 2014 they published their findings on the fimbriae of the Proteus organism.¹⁰ Fimbriae are small pili, or adherence factors, found on the surface of a bacterium (more often on gram-negative bacteria than on gram-positive bacteria), which allow the bacteria to attach to urinary tract tissue and prevent them from being easily dislodged.¹¹ Pearson’s group also found that the fimbriae of the Proteus bacterium are more numerous than those of other bacteria, allowing Proteus to more easily attach to tissue than, say, Salmonella enterica.⁵ Thus, Proteus is more likely than other uropathogenic agents to cause a kidney stone, in part because of the “stickiness” of its many fimbriae.

While stones with an infectious cause are less common than others, they are a danger to our most fragile patients. Thus, when an infectious kidney stone forms, it will require aggressive treatment and a hard-hitting plan to minimize recurrence. Proteus is an especially virulent organism that will require all our resources to overcome it.

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-165.

2. National Kidney Foundation. Diet and kidney stones. kidney.org/atoz/content/diet.cfm. Accessed October 1, 2104.

3. University of Michigan Health System. Bacterium that causes kidney stones and complicated urinary tract infections gives up its genetic secrets (2006). ScienceDaily. sciencedaily.com/releases/2006/05/060524125023.htm. Accessed October 1, 2014.

4. Torzewska A, Budzyńska A, Białczak-Kokot M, Różalski A. In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development. Microb Pathog. 2014;71-72:25-31.

5. Pearson MM, Sebaihia M, Churcher C, et al. Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol. 2008;190(11):4027-4037.

6. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

7. Rowe CM, Ghei M, Adamska E. Moans, groans and renal stones: an interesting case of abdominal pain. BMJ Case Rep. 2013 Nov 4.

8. Chew R, Thomas S, Mantha ML, et al. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81(8):802.

9. Shields J, Maxwell AP. Acute pyelonephritis can have serious complications. Practitioner. 2010;254(1728):19, 21, 23-24.

10. Kuan L, Schaffer JN, Zouzias CD, Pearson MM. Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation. J Med Microbiol. 2014;63(pt 7):911-922.

11. Proft T, Baker EN. Pili in Gram-negative and Gram-positive bacteria: structure, assembly and their role in disease. Cell Mol Life Sci. 2009;66(4):613-635.

The incidence of kidney stones in the United States is as high as 11% among men and 6% among women.¹ This translates into a 1-in-11 risk nationwide, with white men being at greater risk than any other cohort. However, for those patients with high-risk medical issues, such as metabolic syndrome, chronic indwelling urinary catheters, frequent catheterization, and/or recurrent urinary tract infections (UTIs), kidney stones are even more common.² Often, the cause of the stones in at-risk patients is an infection. The most frequent source of UTIs is Escherichia coli, but more complicated infections are often caused by Proteus mirabilis.³ Seventy percent of the stones resulting from UTIs are attributed to P mirabilis.⁴

In 2008, a group of microbiology researchers led by Melanie Pearson, PhD, were able to isolate the genome sequence of P mirabilis.⁵Proteus is a gram-negative enteric bacterium that is often found in complicated UTIs. Proteus is more common among patients with the aforementioned high-risk medical issues and is a particularly common cause of UTIs in the nursing home population (particularly in residents with indwelling catheters).³ It is also a potential cause of kidney stones.

While calcium stones are the most common type of stones,¹ infections, though uncommon, are a secondary source. Stones resulting from infection are imminently treatable; the difficulty is in isolating the source of the infection. Proteus is a particularly toxic, difficult-to treat bacterium that can become resistant to antibiotics.³Proteus produces the enzyme urease, which can reduce the acidity of the urine, allowing stones to form. Once stone formation begins, bacteria can sequester within the stone, making them less susceptible to antibiotic treatment.

Proteus often seems to occur randomly. It has been found as a cause of kidney stones, for example, in a patient who four months earlier underwent transurethral resection of the prostate.⁷Proteus has been reported in a nursing home patient with dementia but no known risk factors.⁸Proteus can cause a pyelonephritis to coalesce into a stone; this complicates what is already an insult to the urinary tract and makes treatment all the more complicated.⁹

Pearson’s group from the University of Michigan has spent the past 10 years sequencing the Proteus bacterium in order to try to gain a foothold in the fight against the infection and the kidney stones it can produce. In 2014 they published their findings on the fimbriae of the Proteus organism.¹⁰ Fimbriae are small pili, or adherence factors, found on the surface of a bacterium (more often on gram-negative bacteria than on gram-positive bacteria), which allow the bacteria to attach to urinary tract tissue and prevent them from being easily dislodged.¹¹ Pearson’s group also found that the fimbriae of the Proteus bacterium are more numerous than those of other bacteria, allowing Proteus to more easily attach to tissue than, say, Salmonella enterica.⁵ Thus, Proteus is more likely than other uropathogenic agents to cause a kidney stone, in part because of the “stickiness” of its many fimbriae.

While stones with an infectious cause are less common than others, they are a danger to our most fragile patients. Thus, when an infectious kidney stone forms, it will require aggressive treatment and a hard-hitting plan to minimize recurrence. Proteus is an especially virulent organism that will require all our resources to overcome it.

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-165.

2. National Kidney Foundation. Diet and kidney stones. kidney.org/atoz/content/diet.cfm. Accessed October 1, 2104.

3. University of Michigan Health System. Bacterium that causes kidney stones and complicated urinary tract infections gives up its genetic secrets (2006). ScienceDaily. sciencedaily.com/releases/2006/05/060524125023.htm. Accessed October 1, 2014.

4. Torzewska A, Budzyńska A, Białczak-Kokot M, Różalski A. In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development. Microb Pathog. 2014;71-72:25-31.

5. Pearson MM, Sebaihia M, Churcher C, et al. Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol. 2008;190(11):4027-4037.

6. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

7. Rowe CM, Ghei M, Adamska E. Moans, groans and renal stones: an interesting case of abdominal pain. BMJ Case Rep. 2013 Nov 4.

8. Chew R, Thomas S, Mantha ML, et al. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81(8):802.

9. Shields J, Maxwell AP. Acute pyelonephritis can have serious complications. Practitioner. 2010;254(1728):19, 21, 23-24.

10. Kuan L, Schaffer JN, Zouzias CD, Pearson MM. Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation. J Med Microbiol. 2014;63(pt 7):911-922.

11. Proft T, Baker EN. Pili in Gram-negative and Gram-positive bacteria: structure, assembly and their role in disease. Cell Mol Life Sci. 2009;66(4):613-635.