An iron-regulated outer-membrane protein of Proteus mirabilis is a haem receptor that plays an important role in urinary tract infection and in in vivo growth

Laboratorio de Microbiología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Av. Italia 3318, CP 11600, Montevideo, Uruguay Correspondence Claudia Piccini piccini{at}iibce.edu.uy Received 29 March 2007 Accepted 15 August 2007 Proteus mirabilis , a common cause of urinary tract infections, expresses iron-regulated outer-membrane proteins (OMPs) in response to iron restriction. It has been suggested that a 64 kDa OMP is involved in haemoprotein uptake and that this might have a role in pathogenesis. In order to confirm this hypothesis, this study generated a P. mirabilis mutant strain (P7) that did not express the 64 kDa OMP, by insertion of the Tn phoA transposon. The nucleotide sequence of the interrupted gene revealed that it corresponded to a haemin receptor precursor. Moreover, in vitro growth assays showed that the mutant was unable to grow using haemoglobin and haemin as unique iron sources. The authors also carried out in vivo growth and infectivity assays and demonstrated that P7 was not able to survive in an in vivo model and was less efficient than wild-type strain Pr 6515 in colonizing the urinary tract. These results confirmed that the P. mirabilis 64 kDa iron-regulated OMP is a haem receptor that has an important role for survival and multiplication of these bacteria in the mammalian host and in the development of urinary tract infection. Abbreviations: Amp, ampicillin; EDDHA, di- o -hydroxyphenylacetic acid; GaPPIX, gallium protoporphyrin IX; Hb, haemoglobin; Hm, haemin; IPC, intraperitoneal chamber; Km, kanamycin; OMP, outer-membrane protein; Tet, tetracycline; UTI, urinary tract infection.