Biological cost of aminoglycoside resistance Arm/Kam 16S rRNA methyltransferases from natural antibiotic producers and clinical pathogens

Vidučić, Darija; Obranić, Sonja; Matovina, Mihaela; Babić, Fedora; Maravić-Vlahoviček, Gordana (2025) Biological cost of aminoglycoside resistance Arm/Kam 16S rRNA methyltransferases from natural antibiotic producers and clinical pathogens. Antimicrobial Agents and Chemotherapy, 69 (9). ISSN 0066-4804

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Abstract

16S rRNA methyltransferases have emerged as critical elements of high-level aminoglycoside resistance in clinical pathogens. We investigated the fitness costs associated with the expression of six methyltransferases isolated from clinical strains (ArmA, RmtA, RmtB, RmtC, RmtD, and NpmA), and two methyltransferases from natural antibiotic producers (Sgm and KamB) in Escherichia coli. Growth competition assays revealed that methyltransferases found in natural producers imposed significantly lower fitness costs than those isolated from clinical strains, allowing resistant populations to persist at stable levels. Translational fidelity assays demonstrated that most methyltransferases induce error-prone phenotypes by allowing increased readthrough of nonsense codons and frameshift mutations, while KamB uniquely increased translational accuracy. Deletion of the housekeeping methyltransferase RsmF further altered these effects, highlighting the complex interplay between endogenous and exogenous methylation processes. Stress response experiments showed varying results: most methyltransferases increased susceptibility to hyperosmotic stress, while several (RmtB, RmtA, ArmA, and KamB) increased tolerance to acidic stress. These findings reveal that 16S rRNA methyltransferases play complex roles in bacterial physiology beyond antibiotic resistance, with important implications for the persistence of resistance and potential therapeutic strategies targeting specific vulnerabilities in resistant bacteria.

Item Type:	Article
Uncontrolled Keywords:	bacterial fitness; fitness cost; aminoglycoside resistance; 16S rRNA methyltransferases
Subjects:	NATURAL SCIENCES > Biology > Microbiology BIOMEDICINE AND HEALTHCARE > Pharmacy
Divisions:	Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Integrating research in molecular life sciences at the University of Zagreb-INTEGRA-LIFE Gordan Lauc; Vlatka Zoldoš; Ita Gruić-Sovulj; Kristian Vlahoviček; Ivana Weygand Đurašević; Jasmina Rokov Plavec; Gordana Maravić Vlahoviček 315997 EK Molekularne osnove djelovanja antibiotika i mehanizmi bakterijske rezistencije- Gordana Maravić Vlahoviček 006-0982913-1219 MZOS
Depositing User:	Lorena Palameta
Date Deposited:	04 Sep 2025 08:06
URI:	http://fulir.irb.hr/id/eprint/9965
DOI:	10.1128/aac.00742-25

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