Neisseria gonorrhoeae Strain with High-Level Resistance to Spectinomycin Due to a Novel Resistance Mechanism (Mutated Ribosomal Protein S5) Verified in Norway

Abstract

Gonorrhea may become untreatable, and new treatment options are essential. Verified resistance to spectinomycin is exceedingly rare. However, we describe a high-level spectinomycin-resistant (MIC, >1,024 g/ml) Neisseria gonorrhoeae strain from Norway with a novel resistance mechanism. The resistance determinant was a deletion of codon 27 (valine) and a K28E alteration in the ribosomal protein 5S. The traditional spectinomycin resistance gene (16S rRNA) was wild type. Despite this exceedingly rare finding, spectinomycin available for treatment of ceftriaxone-resistant urogenital gonorrhea would be very valuable.

The Loop 2 Region of Ribosomal Protein uS5 Influences Spectinomycin Sensitivity, Translational Fidelity, and Ribosome Biogenesis

“…In Bacillus subtilis, G27V and K25I, as well as deletion of Arg30 (equivalent to Ile29 in E. coli), all confer spectinomycin resistance (21)(22)(23). In Neisseria gonorrhoeae, T23P and ΔV24/K25E alterations confer resistance (24,25), while in Pasteurella multocida, S31I/ΔF32 and ΔK22 alterations have been identified in resistant strains (26).…”

Surveillance of the Antimicrobial Susceptibility of <i>Neisseria gonorrhoeae</i> Isolates Collected in Changsha, China from 2003 to 2015

“…Firstly, it is only effective for urethral and rectal infections but not for pharyngeal infections, which are asymptomatic but increasingly common, particularly in men who have sex with men (21). Secondly, a novel mechanism for the generation of high level of SPT resistance was recently reported in a Norwegian strain because of mutations in the gonococcal gene encoding ribosomal protein S5 (22). Third-generation cephalosporins are the recommended antibiotics for the treatment of gonorrhea, and the popularity of these drugs has been maintained in guidelines and the clinical practice of gonorrhea treatment.…”

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

“…For gonococci, high-level spectinomycin resistance (MICs of Ͼ1,024 g/ml) was early shown to be caused by a C1192U SNP in the spectinomycin-binding region of helix 34 in 16S rRNA, including the cross-linked positions 1063 to 1066 and 1190 to 1193 (221,222). Recently, a deletion of Val25 and a K26E alteration in the 30S ribosomal protein S5, encoded by the rpsE gene, were also verified to result in high-level spectinomycin resistance in gonococci (223). A T24P mutation in S5 resulted in low-level spectinomycin resistance (MIC of 128 g/ml) (223,224).…”

“…Recently, a deletion of Val25 and a K26E alteration in the 30S ribosomal protein S5, encoded by the rpsE gene, were also verified to result in high-level spectinomycin resistance in gonococci (223). A T24P mutation in S5 resulted in low-level spectinomycin resistance (MIC of 128 g/ml) (223,224). The N terminus of S5, specifically amino acids 21 to 35, forms a loop that can bind to helix 34 of 16S rRNA and is also involved in spectinomycin binding to the ribosome (225).…”