Neisseria meningitidis (meningococcus) causes invasive meningococcal disease (IMD) which has a mortality rate of 6%. Disease is predominantly caused by serogroups A, B, C, W, X or Y. Multi-locus sequence typing (MLST) classifies meningococci into sequence types (ST) and clonal complexes (cc). Recent global outbreaks have been caused by meningococcal serogroup W (MenW) belonging to the cc11 lineage. MenW has become the predominant cause of IMD in Australia since 2016.
The aim of this study was to analyse the whole-genome sequences of invasive MenW:cc11 from Western Australia (WA) and investigate changes in antibiotic susceptibility.
Genomic DNA of 33 MenW:cc11 strains isolated from patients in WA were sequenced using Illumina paired-ends. Raw reads were assembled and curated using the BIGSdb genomics platform from the PubMLST database.
In WA, the first MenW:cc11 case appeared in 2013. This was followed by two cases in 2014, three cases in 2015, 13 cases in 2016 and 14 cases in 2017. In this collection, six different STs were identified – ST-11 (n=17), ST-1287 (n=3), ST-3298 (n=1) and ST-12351 (n=10), ST-13125 (n=1) and ST-13135 (n=1). Resistance to ciprofloxacin or rifampicin was not identified. However, variation in penicillin susceptibility was observed: 10 isolates showed high susceptibility (MIC=0.064 mg/L) and 23 isolates were resistant (0.25–0.5 mg/L). Core genome phylogeny identified two main clusters, A and B. All penicillin-susceptible isolates fell in Cluster A and possessed the penA_59 allele. The penicillin-resistant meningococci, all isolated in 2016 and 2017, fell in cluster B and possessed the penA_253 allele. Exchange of penA_59 for penA_253 in Cluster A isolates resulted in a significant increase in penicillin MIC. Finally, one outlier strain isolated from a traveler encoded a novel penA allele. This allele conferred reduced susceptibility to penicillin and to the extended-spectrum cephalosporin ceftriaxone.
In conclusion, core-genome analysis identified the emergence of a new cluster of penicillin-resistant MenW:cc11 in WA in 2016 which is currently expanding alarmingly and may thus impact treatment regimens internationally.