Abstract

Proteus spp. are commensal Enterobacterales of the human digestive tract. At the same time, P. mirabilis is commonly involved in urinary tract infections (UTI). P. mirabilis is naturally resistant to several antibiotics including colistin and shows reduced susceptibility to imipenem. However higher levels of resistance to imipenem commonly occur in P. mirabilis isolates consecutively to the loss of porins, reduced expression of penicillin binding proteins (PBPs) PBP1a, PBP2, or acquisition of several antibiotic resistance genes, including carbapenemase genes. In addition, resistance to non-β-lactams is also frequently reported including molecules used for treating UTI infections (e.g., fluoroquinolones, nitrofurans). Emergence and spread of multidrug resistant P. mirabilis isolates, including those producing ESBLs, AmpC cephalosporinases and carbapenemases, are being more and more frequently reported. This review covers Proteus spp. with a focus on the different genetic mechanisms involved in the acquisition of resistance genes to multiple antibiotic classes turning P. mirabilis into a dreadful pandrug resistant bacteria and resulting in difficult to treat infections.

Highlights

  • Proteus spp. are Gram-negative rods belonging to the order of Enterobacterales and the family of Morganellaceae

  • Proteus mirabilis can be found in a wide variety of environments, including soil, water sources, and sewage, but it is predominantly a commensal of the gastrointestinal tracts of humans and animals

  • P. mirabilis is a bacterium of medical importance and usually responsible for most of the common nosocomial opportunistic infections, including those of wounds, the eye, the gastrointestinal tract, and the urinary tract, it is an agent of catheter biofilm formation, quickly fouling the surface of a newly inserted urinary catheter

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Summary

INTRODUCTION

Proteus spp. are Gram-negative rods belonging to the order of Enterobacterales and the family of Morganellaceae. ESBLs are mutant, plasmid-mediated β-lactamases derived from older, broad-spectrum β-lactamases (e.g., TEM-1, TEM-2, SHV-1), which have an extended substrate profile allowing hydrolysis of expanded spectrum cephalosporins, penicillins, and aztreonam These enzymes are most commonly produced by Klebsiella spp. and E. coli but may occur in other gram-negative bacteria, including Morganellaceae. As for ESBL, ampC and carbapenemase genes, resistance genes to other antibiotic families such quinolones (qnr, aac6’Ib) and to aminoglycosides (APH, AAC, AAD, methylases) are more and more frequently identified in P. mirabilis. These genes are carried on mobile genetic elements such as plasmids, transposons, mobile genomic islands, and on integrons that can be mobilized through various mobile elements. The mechanism of mobilization of resistance genes through a rolling circle transposition/recombination process is still not fully understood

Insertion Sequences and Transposons
Wild type Penicillinase IRTb
VEB Enzymes
Findings
CONCLUSION
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