2213. Urease Activity is Enhanced During Co-culture of Common CAUTI Pathogens and Contributes to Severity of Disease in a Murine Infection Model
Session: Poster Abstract Session: Microbial Pathogenesis
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Armbruster_2016.pdf (900.8 kB)
  • Background: Indwelling urinary catheters are often colonized with urease-producing bacteria leading to clinical consequences such as catheter blockage and stones. We showed that co-culture of Proteus mirabilis and Providencia stuartii enhances urease activity and increases infection severity in a murine model of UTI. In this study, we extend our findings to a CAUTI model, utilize urease mutants, and screen for enhanced activity with other pathogens. 

    Methods: Mice were transurethrally inoculated with 107 CFU of P. mirabilis or P. stuartii alone (N=31) or a 50:50 mix (N=23). For CAUTI, mice were inoculated with 105 CFU of P. mirabilis or P. stuartii alone (N=37) or a 50:50 mix (N=20) and a 4 mm segment of silicone catheter was retained in the bladder. Mice were euthanized 4 days post-inoculation to quantify bacterial burden. Urease activity was measured at 30-min intervals during culture of bacteria in human urine.

    Results: Coinfected mice exhibited higher urine pH and more stones despite a similar bacterial burden (Table 1). In the CAUTI model, 95% of coinfections progressed to bacteremia compared to 65% of single infections (P<0.012). Urease was required for increased urine pH, stone formation, and bacteremia during coinfection as these complications were abrogated in studies using urease mutants. Enhanced urease activity also occurred during co-culture of P. mirabilis with Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii.

    Table 1. Coinfection increases disease severity in experimental UTI and CAUTI.

    Single

    Infection

    Coinfection

    P-value

    UTI

    Log10 CFU

    6.94 ± 7.42

    6.90 ± 6.85

    .133

    pH

    7.13 ± 0.63

    7.62 ± 0.46

    .003*

    Stones

    2 (6)

    8 (35)

    .008*

    Bacteremia

    9 (29)

    12 (52)

    .085

    CAUTI

    Log10 CFU

    7.27 ± 7.81

    7.32 ± 7.36

    .037*

    Stones

    3 (8)

    5 (25)

    .080

    Bacteremia

    24 (65)

    19 (95)

    .012*

    Data are mean ± standard deviation for urine CFU and pH (Student’s t test), or number (percent) of urinary stones and bacteremia (chi-square).

    Conclusion: Co-culture of common CAUTI pathogens enhances total urease activity, increasing urinary stones and bacteremia. The mechanism of enhanced urease activity may represent a novel target for limiting detrimental consequences of catheter colonization by urease-producing bacteria.

    Chelsie Armbruster, PhD1, Sara Smith, BS LVT2, Alexandra Johnson, BS2, Valerie Deornelles, MS2, Kathryn Eaton, DVM PhD2, Lona Mody, MD, MSc3 and Harry Mobley, PhD2, (1)Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, (2)University of Michigan Medical School, Ann Arbor, MI, (3)Department of Internal Medicine, Division of Geriatric and Palliative Medicine, University of Michigan Medical School, Ann Arbor, MI

    Disclosures:

    C. Armbruster, None

    S. Smith, None

    A. Johnson, None

    V. Deornelles, None

    K. Eaton, None

    L. Mody, None

    H. Mobley, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.