Azithromycin is increasingly being used for the treatment of shigellosis despite a lack of interpretative guidelines and with limited clinical evidence. The present study determined azithromycin susceptibility and correlated this with macrolide-resistance genes in
Shigella
spp. isolated from stool specimens in Vellore, India. The susceptibility of 332
Shigella
isolates to azithromycin was determined using the disc diffusion method. Of these, 31 isolates were found to be azithromycin resistant. The azithromycin minimum inhibitory concentration (MIC) was determined using the broth microdilution method. In addition, isolates were screened for mphA and ermB genes using conventional PCR. Furthermore, an isolate that was positive for resistance genes was subjected to complete genome analysis, and was analysed for mobile genetic elements. The azithromycin MIC for the 31 resistant
Shigella
isolates ranged between 2 and 16 mg l−1. PCR results showed that a single isolate of
Shigella sonnei
carried a mphA gene. Complete genome analysis revealed integration of an IncFII plasmid into the chromosome of
S. sonnei
, which was also found to carry the following resistance genes: sul1, bla
DHA1, qnrB4, mphA, tetR. Mutations in the quinolone-resistance-determining region (QRDR) were also observed. Additionally, prophages, insertion sequences and integrons were identified. The novel finding of IncFII plasmid integration into the chromosome of
S. sonnei
highlights the potential risk of
Shigella
spp. becoming resistance to azithromycin in the future. These suggests that it is imperative to monitor
Shigella
susceptibility and to study the resistance mechanism of
Shigella
to azithromycin considering the limited treatment choices for shigellosis.
Hybrid genome assembly of Shigella sonnei reveals the novel finding of chromosomal integration of an IncFII plasmid carrying a mphA gene
