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Proteus mirabilis is a Gram-negative, rod-shaped bacterium commonly associated with catheter-associated urinary tract infections (CAUTIs), largely due to its swarming motility and urease activity. These infections are often preceded by urolithiasis, including bladder and kidney stone formation. Aminoglycosides have traditionally been effective in treating a broad range of bacterial infections by binding to the A-site of 16S rRNA in the 30S ribosomal subunit, thereby inhibiting protein synthesis. However, resistance to aminoglycosides has emerged due to the acquisition of aminoglycoside-modifying enzymes such as acetyltransferases, phosphotransferases, and nucleotidyltransferases. More concerning is the recent global dissemination of plasmid-mediated 16S rRNA methyltransferase genes—rmtA, rmtB, and rmtC, which confer high-level resistance and pose a serious clinical threat. In this study, P. mirabilis isolates were molecularly confirmed through amplification of the ureC gene. Antimicrobial susceptibility to aminoglycosides was assessed using the Kirby-Bauer disc diffusion method and broth microdilution assays. The presence of 16S rRNA methylase genes in resistant isolates was subsequently detected via PCR.
References
1. Schwarzhoff RH, Williams RP. Formation of swarming growth patterns by Proteus mirabilis. Journal of Bacteriology. 1978;134(1):10–16.
2. Adeolu M, Alnajar S, Naushad S, Gupta RS. Genome-based phylogeny and taxonomy of the ‘Enterobacteriales’: Proposal for Enterobacterales ord. nov. divided into the families Enterobacteriaceae, Erwiniaceae fam. nov., Pectobacteriaceae fam. nov., Yersiniaceae fam. nov., Hafniaceae fam. nov., Morganellaceae fam. nov., and Budviciaceae fam. nov. International Journal of Systematic and Evolutionary Microbiology. 2016;66(12): 5575–5599.
3. O’Hara CM, Brenner FW, Miller JM.Classification, identification, and clinical significance of Proteus, Providencia, and Morganella. Clinical Microbiology Reviews. 2000;13(4):534–546.
4. Schaffer JN, Pearson MM. Proteus mirabilis and urinary tract infections. Microbiology Spectrum. 2015; 3(5).
5. Foris LA, Snowden J. Proteus mirabilis. In StatPearls. StatPearls Publishing. 2017.
6. Armbruster CE, Mobley HLT. Merging mythology and morphology: The multifaceted lifestyle of Proteus mirabilis. Nat Rev Microbiol. 2012;10(11):743-54.
7. Warren JW, Platt R, Thomas RJ, Rosener B, Kass EH. Antibiotic treatment of bacteriuria in patients with indwelling catheters: A clinical trial. Ann Intern Med. 1982;97(5):713-8.
8. Kim BN, Woo JH, Kim MN, Ryu J, Kim YS. Clinical significance and outcomes of bacteremia caused by Proteus species. Korean J Intern Med. 2003;18(2):87-93.
9. Hung CH, Lin CH, Lin HY. Proteus mirabilis bacteremia: Risk factors and clinical characteristics. South Med J. 2007;100(8):783-7.
10. Stickler DJ, Morgan SD, Winters C. Clinical challenge: biofilms and bladder stones. Clin Infect Dis. 2006;43(5):652-7.
11. Coker C, Poore CA, Li X, Mobley HLT. Pathogenesis of urinary tract infection. Curr Opin Microbiol. 2000;3(1):65-70.
12. Foxman B, Brown P. Epidemiology of urinary tract infections: Transmission and risk factors, incidence, and costs. Infect Dis Clin North Am. 2003;17(2):227-41.
13. Mansy SS. Proteus mirabilis meningitis in an adult. J Infect. 2001;42(2):130-1.
14. Watanakunakorn C, Perni SC. Proteus mirabilis bacteremia: A review of 176 cases at a community teaching hospital. South Med J. 1994;87(2):258-60.
15. Kotra LP, Haddad J, Mobashery S. Aminoglycosides: Perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrob Agents Chemother. 2000;44(12):3249-56.
16. Shaw KJ, Rather PN, Hare RS, Miller GH. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev. 1993;57(1):138-63.
17. Wachino J, Arakawa Y. Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: An update. Drug Resist Updat. 2012;15(3):133-48.
18. Galimand M, Sabtcheva S, Courvalin P, Lambert T. Worldwide dissemination of the 16S rRNA methylase armA gene among Gram-negative rods. Emerg Infect Dis. 2003;9(6):810-3.
19. Doi Y, Arakawa Y. 16S ribosomal RNA methylation: Emerging resistance mechanism against aminoglycosides. Clin Infect Dis. 2007;45(1):88-94.
20. Lee K, Lee WG, Uh Y, Ha GY, Cho J, Chong Y. VIM- and IMP-type metallo-β-lactamase-producing Pseudomonas spp. and Acinetobacter spp. in Korean hospitals. Emerg Infect Dis. 2006;12(8):1468-71.
21. Yamane K, Wachino J, Suzuki S, Kimura K, Shibata N, Kato H. New plasmid-mediated 16S rRNA methyltransferase, RmtC, found in a Proteus mirabilis clinical strain isolated in Japan. Antimicrob Agents Chemother. 2007;51(12):4401-4.
22. Yokoyama K, Doi Y, Yamane K, Kurokawa H, Shibata N, Shibayama K. Acquisition of 16S rRNA methylase gene rmtA in Pseudomonas aeruginosa. Lancet. 2003;362(9391):1888-93.
23. Yu Y, Zhou H, Xu X, Zhang J, Chen Y, Zhou Y, et al. Prevalence of 16S rRNA methylase genes among panaminoglycoside-resistant isolates of Gram-negative bacteria. J Clin Microbiol. 2007;45(3):881-5.
24. Tanvir F, Ahmad FJ, Khalid N, Javed MT. Characterization and antibiotic susceptibility pattern of bacterial pathogens from urinary tract infection in Gujranwala, Pakistan. Biologia (Pakistan). 2012;58(1–2):109-14.
25. Sambrook J, Russell DW. Molecular Cloning: A Laboratory Manual. 3rd ed. Cold Spring Harbor Laboratory Press; 2001.
26. Takeuchi K, Kato Y, Ohno T. Detection of Proteus mirabilis using urease gene-specific primers. Microbiol Immunol. 1996;40(11):827-31.
27. Jacobsen SM, Stickler DJ, Mobley HLT, Shirtliff ME. Complicated catheter-associated urinary tract infections due to Escherichia coli and Proteus mirabilis. Clin Microbiol Rev. 2008;21(1):26-59.
28. Mobley HLT, Chippendale GR, Swihart KG. Cytotoxicity of Proteus mirabilis hemolysin to human renal cell lines. Infect Immun. 1995;63(1):102-7.
29. Wachino J, Yamane K, Kimura K, Shibayama K, Suzuki S, Ike Y. Novel plasmid-mediated 16S rRNA methylase, RmtD, found in a Proteus mirabilis isolate from Brazil. Antimicrob Agents Chemother. 2007;51(4):1380-2.
30. Foxman B. Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs. Dis Mon. 2002;49(2):53-70.
31. Bonacorsi S, Clermont O, Houdouin V, Cordevant C, Brahimi N, Bingen E. Molecular analysis and experimental virulence of French human Escherichia coli strains producing CTX-M beta-lactamases. J Antimicrob Chemother. 2006;58(4):744-9.
32. CLSI. Performance Standards for Antimicrobial Susceptibility Testing; 25th Informational Supplement (M100-S25). Clinical and Laboratory Standards Institute. 2015.
33. Drzewiecka D. Significance and roles of Proteus spp. bacteria in natural environments. Microb Ecol. 2016;72(4):741-58.
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