Penicillin and extended-spectrum cephalosporin resistance has been associated with mutations and recombination within the penA, porinB, and ponA genes and the presence of bla and involves a complex interaction [12].
Interestingly, resistance to penicillin was intermediate, although there were two different mutations in the porinB gene (cephinase testing was negative). Unfortunately, there is no additional information on allele type 55 at NG-STAR (regarding origin, MICs or epidemiological data). Furthermore, the mutations G120N and A121G are available only in combination with other mutations in all other allele types but not as single mutations (based on information from NG-STAR). The combination of G120N and A121G in Switzerland has also not been previously reported in publications with extensive datasets [13].
The ponA (penicillin binding-protein 1, PBP1) mutation L421P also seems to be a widespread mutation [5] in Switzerland [13]. According to NG-STAR, this mutation has been observed in Ng with elevated cephalosporin MICs, although the L421P mutation has not been shown to cause resistance in transformation experiments [7].
NG-STAR does not provide additional information on penA allele-type 148 NonMosaic with the A517G mutation (regarding origin, MICs or epidemiological data). The most recent literature only confirms the dependence of A517G on MICs for extended-spectrum cephalosporins (ceftriaxone and cefixime) [12]. For penA (penicillin binding-protein 2, PBP2), diverse sequence variations were observed (i.e., 363 entries for allele types in the NG-STAR database).
The deletion of an adenine in the mtr promoter region may reduce susceptibility to different drugs and is also widespread [5, 13].
The elevated MIC for ciprofloxacin was due to 2 different mutations of the gyrA gene as well as 1 mutation of the parC gene. The combination of gyrA (S91F, D95A) and parC (S87R) mutations was previously observed in locations other than Switzerland [5, 13, 14]. Two strains with the same combination of gyrA and parC found in Switzerland [13] had a lower MIC (of 1.5 and 3 mg/l) than the strain in this study (Table 1).
Azithromycin is below the ECOFF and is consistent with the wild-type allele. Due to phenotypic susceptibility towards tetracycline, we did not additionally sequence the corresponding genes tetM and rpsJ [11, 15].
It remains unclear whether this particular strain was imported from abroad or evolved due to the selective pressure of applied antibiotics or patient noncompliance.
The observed combination of mutations is, to the best of our knowledge, at least very unusual (since it has not been mentioned in different recent publications, e.g., [5, 12, 13, 16, 17]) and has not been previously described in Switzerland. Resistance mechanisms remain complex due to the many combination possibilities [12]. Therefore, our findings contribute to a more extensive knowledge of Ng phenotypes and genotypes.