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Evolution and spread of a multidrug-resistant Proteus mirabilis clone with chromosomal AmpC-type cephalosporinases in Europe.

ABSTRACT: Proteus mirabilis isolates obtained in 1999 to 2008 from three European countries were analyzed; all carried chromosomal AmpC-type cephalosporinase bla(CMY) genes from a Citrobacter freundii origin (bla(CMY-2)-like genes). Isolates from Poland harbored several bla(CMY) genes (bla(CMY-4), bla(CMY-12), bla(CMY-14), bla(CMY-15), and bla(CMY-38) and the new gene bla(CMY-45)), while isolates from Italy and Greece harbored bla(CMY-16) only. Earlier isolates with bla(CMY-4) or bla(CMY-12), recovered in France from Greek and Algerian patients, were also studied. All isolates showed striking similarities. Their bla(CMY) genes resided within ISEcp1 transposition modules, named Tn6093, characterized by a 110-bp distance between ISEcp1 and bla(CMY), and identical fragments of both C. freundii DNA and a ColE1-type plasmid backbone. Moreover, these modules were inserted into the same chromosomal site, within the pepQ gene. Since ColE1 plasmids carrying ISEcp1 with similar C. freundii DNA fragments (Tn6114) had been identified earlier, it is likely that a similar molecule had mediated at some stage this DNA transfer between C. freundii and P. mirabilis. In addition, isolates with bla(CMY-12), bla(CMY-15), and bla(CMY-38) genes harbored a second bla(CMY) copy within a shorter ISEcp1 module (Tn6113), always inserted downstream of the ppiD gene. Sequence analysis of all mobile bla(CMY-2)-like genes indicated that those integrated in the P. mirabilis chromosome form a distinct cluster that may have evolved by the stepwise accumulation of mutations. All of these observations, coupled to strain typing data, suggest that the bla(CMY) genes studied here may have originated from a single ISEcp1-mediated mobilization-transfer-integration process, followed by the spread and evolution of a P. mirabilis clone over time and a large geographic area.

SUBMITTER: D'Andrea MM

PROVIDER: S-EPMC3101460 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Evolution and spread of a multidrug-resistant Proteus mirabilis clone with chromosomal AmpC-type cephalosporinases in Europe.

D'Andrea M M MM Literacka E E Zioga A A Giani T T Baraniak A A Fiett J J Sadowy E E Tassios P T PT Rossolini G M GM Gniadkowski M M Miriagou V V

Antimicrobial agents and chemotherapy 20110314 6

Proteus mirabilis isolates obtained in 1999 to 2008 from three European countries were analyzed; all carried chromosomal AmpC-type cephalosporinase bla(CMY) genes from a Citrobacter freundii origin (bla(CMY-2)-like genes). Isolates from Poland harbored several bla(CMY) genes (bla(CMY-4), bla(CMY-12), bla(CMY-14), bla(CMY-15), and bla(CMY-38) and the new gene bla(CMY-45)), while isolates from Italy and Greece harbored bla(CMY-16) only. Earlier isolates with bla(CMY-4) or bla(CMY-12), recovered in ...[more]

PMID: 21402851

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Project description:Catheter-associated urinary tract infections (CAUTI) is an alarming hospital based disease with the increase of multidrug resistance (MDR) strains of Proteus mirabilis. Cases of long term hospitalized patients with multiple episodes of antibiotic treatments along with urinary tract obstruction and/or undergoing catheterization have been reported to be associated with CAUTI. The cases are complicated due to the opportunist approach of the pathogen having robust swimming and swarming capability. The latter giving rise to biofilms and probably inducible through autoinducers make the scenario quite complex. High prevalence of long-term hospital based CAUTI for patients along with moderate percentage of morbidity, cropping from ignorance about drug usage and failure to cure due to MDR, necessitates an immediate intervention strategy effective enough to combat the deadly disease. Several reports and reviews focus on revealing the important genes and proteins, essential to tackle CAUTI caused by P. mirabilis. Despite longitudinal countrywide studies and methodical strategies to circumvent the issues, effective means of unearthing the most indispensable proteins to target for therapeutic uses have been meager. Here, we report a strategic approach for identifying the most indispensable proteins from the genome of P. mirabilis strain HI4320, besides comparing the interactomes comprising the autoinducer-2 (AI-2) biosynthetic pathway along with other proteins involved in biofilm formation and responsible for virulence. Essentially, we have adopted a theoretical network model based approach to construct a set of small protein interaction networks (SPINs) along with the whole genome (GPIN) to computationally identify the crucial proteins involved in the phenomenon of quorum sensing (QS) and biofilm formation and thus, could be therapeutically targeted to fight out the MDR threats to antibiotics of P. mirabilis. Our approach utilizes the functional modularity coupled with k-core analysis and centrality scores of eigenvector as a measure to address the pressing issues.

Project description:ObjectiveProteus mirabilis is the one of most important pathogens of catheter-associated urinary tract infections. The emergence of multidrug-resistant (MDR) P. mirabilis severely limits antibiotic treatments, which poses a public health risk. This study aims to investigate the resistance characteristics and virulence potential for a collection of P. mirabilis clinical isolates.Methods and resultsAntibiotic susceptibility testing revealed fourteen MDR strains, which showed high resistance to most β-lactams and trimethoprim/sulfamethoxazole, and a lesser extent to quinolones. All the MDR strains were sensitive to carbapenems (except imipenem), ceftazidime, and amikacin, and most of them were also sensitive to aminoglycosides. The obtained MDR isolates were sequenced using an Illumina HiSeq. The core genome-based phylogenetic tree reveals the high genetic diversity of these MDR P. mirabilis isolates and highlights the possibility of clonal spread of them across China. Mobile genetic elements SXT/R391 ICEs were commonly (10/14) detected in these MDR P. mirabilis strains, whereas the presence of resistance island PmGRI1 and plasmid was sporadic. All ICEs except for ICEPmiChn31006 carried abundant antimicrobial resistance genes (ARGs) in the HS4 region, including the extended-spectrum β-lactamase (ESBL) gene blaCTX-M-65. ICEPmiChn31006 contained the sole ARG blaCMY-2 and was nearly identical to the global epidemic ICEPmiJpn1. The findings highlight the important roles of ICEs in mediating the spread of ARGs in P. mirabilis strains. Additionally, these MDR P. mirabilis strains have great virulence potential as they exhibited significant virulence-related phenotypes including strong crystalline biofilm, hemolysis, urease production, and robust swarming motility, and harbored abundant virulence genes.ConclusionIn conclusion, the prevalence of MDR P. mirabilis with high virulence potential poses an urgent threat to public health. Intensive monitoring is needed to reduce the incidence of infections by MDR P. mirabilis.

Dataset Information

Evolution and spread of a multidrug-resistant Proteus mirabilis clone with chromosomal AmpC-type cephalosporinases in Europe.

Publications

Evolution and spread of a multidrug-resistant Proteus mirabilis clone with chromosomal AmpC-type cephalosporinases in Europe.

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