Proteus mirabilis has been described as an aetiological agent in a wide range of infections, playing an important role in urinary tract infections (UTIs). In this study, a collection of P. mirabilis isolates obtained from clinical and non-clinical sources was analysed in order to determine a possible correlation between origin, virulence factors and in vivo infectivity. Isolates were characterized in vitro, assessing several virulence properties that had been previously associated with P. mirabilis uropathogenicity. Swarming motility, urease production, growth in urine, outer-membrane protein patterns, ability to grow in the presence of different iron sources, haemolysin and haemagglutinin production, and the presence and expression of diverse fimbrial genes, were analysed. In order to evaluate the infectivity of the different isolates, the experimental ascending UTI model in mice was used. Additionally, the Dienes test and the enterobacterial repetitive intergenic consensus (ERIC)-PCR assay were performed to assess the genetic diversity of the isolates. The results of the present study did not show any correlation between distribution of the diverse potential urovirulence factors and isolate source. No significant correlation was observed between infectivity and the origin of the isolates, since they all similarly colonized the urinary tract of the challenged mice. Finally, all isolates showed unique ERIC-PCR patterns, indicating that the isolates were genetically diverse. The results obtained in this study suggest that the source of P. mirabilis strains cannot be correlated with pathogenic attributes, and that the distribution of virulence factors between isolates of different origins may correspond to the opportunistic nature of the organism.
AdegbolaR. A, OldD. C, SeniorB. W.
1983; The adhesins and fimbriae of Proteus mirabilis strains associated with high and low affinity for the urinary tract. J Med Microbiol 16:427–431[CrossRef]
AllisonC, EmodyL, ColemanN, HughesC.
1994; The role of swarm cell differentiation and multicellular migration in the uropathogenicity of Proteus mirabilis . J Infect Dis 169:1155–1158[CrossRef]
BahraniF. K, MassadG, LockatellC. V, JohnsonD. E, RussellR. G, WarrenJ. W, MobleyH. L.
1994; Construction of an MR/P fimbrial mutant of Proteus mirabilis : role in virulence in a mouse model of ascending urinary tract infection. Infect Immun 62:3363–3371
BaleM, HollisJ.
1992; Characterization of organisms for epidemiologic purposes: serotyping, pyocin typing, and Dienes test. In Clinical Microbiology Procedures Handbook pp 11.14.1–11.14.2 Edited by
IsenbergH. D.
Washington DC: American Society for Microbiology;
BubF, BiekerP, MartinH. H, NixdorffK.
1980; Immunological characterization of two major proteins isolated from the outer membrane of Proteus mirabilis . Infect Immun 27:315–321
BurallL. S, HarroJ. M, LiX, LockatellC. V, HimpslS. D, HebelJ. R, JohnsonD. E, MobleyH. L.
2004; Proteus mirabilis genes that contribute to pathogenesis of urinary tract infection: identification of 25 signature-tagged mutants attenuated at least 100-fold. Infect Immun 72:2922–2938[CrossRef]
CarlbergD. M.
1986; Determining the effects of antibiotics on bacterial growth by optical and electrical methods. In Antibiotics in Laboratory Medicine pp 64–92 Edited by
LorianV.
Baltimore: Williams & Wilkins;
GaastraW, PietersE. W, BergmansH. E, AgnesA,
van OosteromR. A,
van DijkL,
ter HuurneH. M. 1996; Isolation and characterisation of dog uropathogenic Proteus mirabilis strains. Vet Microbiol 48:57–71[CrossRef]
JansenA. M, LockatellC. V, JohnsonD. E, MobleyH. L.
2003; Visualization of Proteus mirabilis morphotypes in the urinary tract: the elongated swarmer cell is rarely observed in ascending urinary tract infection. Infect Immun 71:3607–3613[CrossRef]
JonesB. D, LockatellC. V, JohnsonD. E, WarrenJ. W, MobleyH. L.
1990; Construction of a urease-negative mutant of Proteus mirabilis : analysis of virulence in a mouse model of ascending urinary tract infection. Infect Immun 58:1120–1123
MassadG, LockatellC. V, JohnsonD. E, MobleyH. L.
1994; Proteus mirabilis fimbriae: construction of an isogenic pmfA mutant and analysis of virulence in a CBA mouse model of ascending urinary tract infection. Infect Immun 62:536–542
MoayeriN, CollinsC. M, O'HanleyP.
1991; Efficacy of a Proteus mirabilis outer membrane protein vaccine in preventing experimental pyelonephritis in a BALB-c mouse model. Infect Immun 59:3778–3786
MobleyH. L, ChippendaleG. R.
1990; Hemagglutinin, urease, and hemolysin production by Proteus mirabilis from clinical sources. J Infect Dis 161:525–530[CrossRef]
MobleyH. L, BelasR, LockatellV, ChippendaleG, TrifillisA. L, JohnsonD. E, WarrenJ. W.
1996; Construction of a flagellum-negative mutant of Proteus mirabilis : effect on internalization by human renal epithelial cells and virulence in a mouse model of ascending urinary tract infection. Infect Immun 64:5332–5340
OelschlaegerT. A, DobrindtU, HackerJ.
2002a; Pathogenicity islands of uropathogenic Escherichia coli and the evolution of virulence. Int J Antimicrob Agents 19:517–521[CrossRef]
OldD. C, AdegbolaR. A.
1985; Antigenic relationships among type-3 fimbriae of Enterobacteriaceae revealed by immunoelectronmicroscopy. J Med Microbiol 20:113–121[CrossRef]
PeerboomsP. G, VerweijA. M, MacLarenD. M.
1983; Investigation of the haemolytic activity of Proteus mirabilis strains. Antonie Van Leeuwenhoek 49:1–11[CrossRef]
PfallerM. A, MujeebI, HollisR. J, JonesR. N, DoernG. V.
2000; Evaluation of the discriminatory powers of the Dienes test and ribotyping as typing methods for Proteus mirabilis . J Clin Microbiol 38:1077–1080
PicciniC. D, Legnani-FajardoC. L,
BarbéF. M. 1998; Identification of iron-regulated outer membrane proteins in uropathogenic Proteus mirabilis and its relationship with heme uptake. FEMS Microbiol Lett 166:243–248[CrossRef]
RobledoJ. A, SerranoA, DomingueG. J.
1990; Outer membrane proteins of Escherichia coli in the host-pathogen interaction in urinary tract infection. J Urol 143:386–391
RussoT. A, JodushS. T, BrownJ. J, JohnsonJ. R.
1996; Identification of two previously unrecognized genes (guaA and argC) important for uropathogenesis. Mol Microbiol 22:217–229[CrossRef]
SandersJ. D, CopeL. D, HansenE. J.
1994; Identification of a locus involved in the utilization of iron by Haemophilus influenzae . Infect Immun 62:4515–4525
TowbinH, StaehelinT, GordonJ.
1979; Electrophoretic transfer of proteins from polyacrylamide gels to nitocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 76:4350–4354[CrossRef]
VersalovicJ, KoeuthT, LupskiJ. R.
1991; Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. Nucleic Acids Res 19:6823–6831[CrossRef]
WarrenJ. W, TenneyJ. H, HoopesJ. M, KassE. H.
1982; A prospective microbiologic study of bacteriuria in patients with chronic indwelling urethral catheters. J Infect Dis 146:719–723[CrossRef]
ZuninoP, PicciniC, Legnani-FajardoC.
1994; Flagellate and non-flagellate Proteus mirabilis in the development of experimental urinary tract infection. Microb Pathog 16:379–385[CrossRef]
ZuninoP, GeymonatL, AllenA. G, Legnani-FajardoC, MaskellD. J.
2000; Virulence of a Proteus mirabilis ATF isogenic mutant is not impaired in a mouse model of ascending urinary tract infection. FEMS Immunol Med Microbiol 29:137–143[CrossRef]
ZuninoP, GeymonatL, AllenA. G, PrestonA, SosaV, MaskellD. J.
2001; New aspects of the role of MR/P fimbriae in Proteus mirabilis urinary tract infection. FEMS Immunol Med Microbiol 31:113–120[CrossRef]
ZuninoP, SosaV, AllenA. G, PrestonA, SchlappG, MaskellD. J.
2003; Proteus mirabilis fimbriae (PMF) are important for both bladder and kidney colonization in mice. Microbiology 149:3231–3237[CrossRef]