Genome Sequencing of a Neisseria gonorrhoeae Isolate of a Successful International Clone with Decreased Susceptibility and Resistance to Extended-Spectrum Cephalosporins

Abstract

ABSTRACTThe recent emergence ofNeisseria gonorrhoeaestrains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. We sequenced the genome of anN. gonorrhoeaemultiantigen sequence typing (NG-MAST) ST1407 isolate (SM-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. The isolate was cultured in 2008 in San Francisco, CA, and possessed mosaicpenAallele XXXIV, which is associated with an international clone that possesses decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins globally. The genome sequence of strain NCCP11945 was used as a scaffold, and our assembly resulted in 91 contigs covering 2,029,064 bp (91%; >150× coverage) of the genome. Numerous instances of suspected horizontal genetic transfer events with otherNeisseriaspecies were identified, and two genes,opaandtxf, acquired from nongonococcalNeisseriaspecies, were identified. Strains possessing mosaicpenAalleles (n= 108) and nonmosaicpenAalleles (n= 169) from the United States and Europe (15 countries), cultured in 2002 to 2009, were screened for the presence of these genes. Theopagene was detected in most (82%)penAmosaic-containing isolates (mainly from 2007 to 2009) but not in anypenAnonmosaic isolates. Thetxfgene was found in all strains containingopabut also in several (18%)penAnonmosaic strains. Usingopaandtxfas genetic markers, we identified a strain that possesses mosaicpenAallele XXXIV, but the majority of its genome is not genetically related to strain SM-3. This implies thatpenAmosaic allele XXXIV was transferred horizontally. Such isolates also possessed decreased susceptibility and resistance to oral extended-spectrum cephalosporins. These findings support that genetic screening for particularpenAmosaic alleles can be a valuable method for tracking strains with decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins worldwide and that screening using only NG-MAST may not be sufficient.